Terminal alkynes react with CO and CH3OH, using a combination of a palladiumII halide and a copperII halide, to give a conjugated diester, MeO2C C CCO2Me.1520A similar reaction with alk
Trang 1CO and H2O as a nucleophile is often called Reppe carbonylation.1497The toxic nature of nickel tetracarbonyl has led to development of other catalysts.1498Indeed, variations in the reaction procedure include the use of Pd,1499Pt,1500and Rh1501 catalysts This reaction converts alkenes, alkynes, and dienes and is tolerant of a wide variety of functional groups When the additive is alcohol or acid, saturated or unsaturated acids, esters, or anhydrides are produced (see Reaction 15-36) The transition metal catalyzed carbonylation has been done enantioselectively, with moderate-to-high optical yields, by the use of an optically active palladium-complex catalyst.1502Alkenes also react with Fe(CO)5and CO to give carboxylic acids.1503 Electrochemical carboxylation procedures have been developed, including the conversion of alkenes to 1,4-butanedicarboxylic acids.1504 A reductive carboxylation of alkenes with CO and cesium carbonate has been reported.1505
When applied to triple bonds, hydrocarboxylation gives a,b-unsaturated acids under very mild conditions Triple bonds give unsaturated acids and saturated dicarboxylic acids when treated with CO2and an electrically reduced Ni complex catalyst.1506Alkynes also react with NaHFe(CO)4, followed by CuCl2 2 H2O, to give alkenyl acid derivatives.1507A related reaction with CO and Pd catalysts in the presence of SnCl2leads to conjugated acid derivatives.1508Terminal alkynes react with CO2and Ni(cod)2(cod ¼ 1,5-cycloctadiene), and subsequent treatment with DBU gives the a,b-unsaturated carboxylic acid.1509
When acid catalysts are employed, in the absence of nickel carbonyl, the mechanism1510involves initial attack on a proton, followed by attack by CO on the resulting carbocation
to give an acyl cation, and subsequent reaction with water gives the product 107 Markovnikov’s rule is followed, and carbon skeleton rearrangements and double-bond isomerizations (prior to attack by CO) are frequent.
D Acc Chem Res.1988, 21, 428; Tsuji, J Acc Chem Res 1969, 2, 144; Bird, C.W Chem Rev 1962, 62, 283.1498
For a review, see Kiss, G Chem Rev.2001, 101, 3435
Brunet, J.-J.; Neibecker, D.; Srivastava, R.S Tetrahedron Lett.1993, 34, 2759
1504Senboku, H.; Komatsu, H.; Fujimura, Y.; Tokuda, M Synlett2001, 418
1505Williams, C.M.; Johnson, J.B.; Rovis, T J Am Chem Soc.2008, 130, 14936
1506Du~nach, E.; Derien, S.; Perichon, J J Organomet Chem 1989, 364, C33
1507Periasamy, M.; Radhakrishnan, U.; Rameshkumar, C.; Brunet, J.-J Tetrahedron Lett.1997, 38, 1623
1508Takeuchi, R.; Sugiura, M J Chem Soc Perkin Trans 1,1993, 1031
1509Saito, S.; Nakagawa, S.; Koizumi, T.; Hirayama, K.; Yamamoto, Y J Org Chem.1999, 64, 3975 See also,Takimoto, M.; Shimizu, K.; Mori, M Org Lett.2001, 3, 3345
1510
See Hogeveen, H Adv Phys Org Chem.1973, 10, 29
Trang 2For the transition metal catalyzed reactions, the nickel carbonyl reaction has been well studied and the addition is syn for both alkenes and alkynes.1511 The following is the accepted mechanism:1511
Step 1 Ni(CO)4 Ni(CO)3 + CO
Ni(CO)3
HNi(CO)3
H
Ni(CO)2O
H
Ni(CO)2O
H
OHO
15-36 Carbonylation, Alkoxycarbonylation, and Aminocarbonylation
of Double and Triple Bonds
Alkyl, Alkoxy, or Amino-carbonyl-addition
HO
R1
R1
HRHN
In the presence of certain metal catalysts, alkenes and alkynes can be carbonylated
or converted to give an amide or an ester.1513There are several variations The reaction
of an alkyl iodide and a conjugated ester with CO, (Me3Si)3SiH, and AIBN in supercritical CO2 (Sec 9.D.ii) gave a g-keto ester.1514 Terminal alkynes react with
1511Bird, C.W.; Cookson, R.C.; Hudec, J.; Williams, R.O J Chem Soc.1963, 410
1512Chen, A.; Ren, L.; Crudden, C.M.; J Org Chem.1999, 64, 9704
1513See Fallis, A.G.; Forgione, P Tetrahedron2001, 57, 5899
1514
Kishimoto, Y.; Ikariya, T J Org Chem.2000, 65, 7656
Trang 3CO and methanol in the presence of CuCl2 and PdCl2 to give a a,b-unsaturated methyl ester.1515 Conjugated dienes react with thiophenol, CO and Pd(OAc)2 to give the b,g-unsaturated thioester.1516 Allene reacts with CO, CH3OH, and a Ru catalyst to give methacrylic acid.1517Alkynes react with thiophenol and CO with a Pd1518or Pt1519catalyst to give a conjugated thioester Terminal alkynes react with CO and CH3OH, using a combination of a palladium(II) halide and a copper(II) halide, to give a conjugated diester, MeO2C C CCO2Me.1520A similar reaction with alkenes using a combination of a Pd and a Mo catalyst led to a saturated diester (MeO2C CCCO2Me).1521 Alkenes were converted to the dimethyl ester of 1,4- butanedioic acid derivatives with CO/O2 and a combination of PdCl2 and CuCl catalysts.1522Note that alkenes primarily are converted to the anti-Markovnikov ester upon treatment with arylmethyl formate esters (ArCH2OCHO) and a Ru catalyst.1523Terminal alkynes react with tosyl azide, water, and a catalytic amount of CuI to give an N-tosyl amide.1524
b-chloro-A bicyclic ketone was generated when 1,2-diphenylethyne was heated with carbon monoxide, methanol and a dirhodium catalyst.15252-Iodostyrene reacted at 100C with
CO and a Pd catalyst to give the bicyclic ketone 1-indanone.1526 Another variation reacted a conjugated allene–alkene with 5 atm of CO and a Rh catalyst to give a bicyclic ketone.1527 An intermolecular version of this reaction is known using a Co catalyst, giving a cyclopentenone1528 in a reaction related to the Pauson–Khand reaction (see below) The reaction of a conjugated diene having a distal alkene unit and CO with a Rh catalyst led to a bicyclic conjugated ketone.1529When a Stille coupling (Reaction 12-15) is done in a CO atmosphere, conjugated ketones of the type C CCOC C are formed,1530
suitable for a Nazarov cyclization (Reaction 15-20) Alkynes were converted to cyclobutenones using Fe3(CO)12to form an initial complex, followed by reaction with copper(II) chloride.1531 An interesting variation treated cyclohexene with 5 molar equivalents of Oxone and a RuCl3catalyst to give 2-hydroxycyclohexanone.1532
1515Li, J.; Jiang, H.; Feng, A.; Jia, L J Org Chem.1999, 64, 5984 See also, Clarke, M.L Tetrahedron Lett
Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S Tetrahedron Lett.1999, 40, 7811
1526Gagnier, S.V.; Larock, R.C J Am Chem Soc.2003, 125, 4804
1527Murakami, M.; Itami, K.; Ito, Y J Am Chem Soc.1999, 121, 4130
1528Jeong, N.; Hwang, S.H Angew Chem Int Ed.2000, 39, 636
1529Lee, S.I.; Park, J.H.; Chung, Y.K.; Lee, S.-G J Am Chem Soc.2004, 126, 2714
1530Mazzola, Jr., R.D.; Giese, S.; Benson, C.L.; West, F.G J Org Chem.2004, 69, 220
1531Rameshkumar, C.; Periasamy, M Tetrahedron Lett.2000, 41, 2719
1532Plietker, B J Org Chem.2004, 69, 8287
Trang 4The reaction of dienes, diynes, or enynes with transition metals1533(usually Co)1534forms organometallic coordination complexes Rhodium,1535 Ti,1536 Mo,1537and W1538complexes have been used for this reaction In the presence of CO, the metal complexes derived primarily from enynes (alkene–alkynes) generate cyclopentenone derivatives in what is known as the Pauson–Khand reaction.1539This reaction involves (1) formation
of a hexacarbonyldicobalt–alkyne complex and (2) decomposition of the complex in the presence of an alkene.1540 A typical example is the preparation of 108.1541
Cyclopentenones can be prepared by an intermolecular reaction of a vinyl silane and
an alkyne using CO and a Ru catalyst.1542 Carbonylation of an alkene–diene using a
Rh catalyst leads to cyclization to an a-vinyl cyclopentanone.1543
An yne–diene can also be used for the Pauson–Khand reaction.1544
SiMe3
MOMO
SiMe3OMOMO H
108
Co2(CO)8 , CO
90 °C , 36 h heptane, sealed tube
The reaction can be promoted photochemically1545 and the rate is enhanced by the presence of primary amines.1546 Coordinating ligands also accelerate the reaction,1547polymer-supported promoters have been developed1548 and there are many possible variations in reaction conditions.1549 The Pauson–Khand reaction has been done under heterogeneous reaction conditions,1550 with Co nanoparticles,1551 and in water.1552 A
1533
See Krafft, M.E.; Hirosawa, C.; Bonaga, L.V.R Tetrahedron Lett.1999, 40, 9177
1534See Krafft, M.E.; Bo~naga, L.V.R.; Hirosawa, C J Org Chem 2001, 66, 3004
1538Hoye, T.R.; Suriano, J.A J Am Chem Soc.1993, 115, 1154
1539Khand, I.U.; Pauson, P.L.; Habib, M.J J Chem Res (S)1978, 348; Khand, I.U; Pauson, P.L J Chem Soc.Perkin Trans 1,1976, 30 Gibson, S.E.; Stevenazzi, A Angew Chem Int Ed 2003, 42, 1800; Gibson, S.E.;Mainolfi, N Angew Chem Int Ed.2005, 44, 3022; Lee, H.-W.; Kwong, F.-Y Eur J Org Chem 2010, 789.1540
See de Bruin, T.J.M.; Milet, A.; Greene, A.E.; Gimbert, Y J Org Chem.2004, 69, 1075 See also, Rivero,M.R.; Adrio, J.; Carretero, J.C Eur J Org Chem.2002, 2881
in aqueous media: Krafft, M.E.; Wright, J.A.; Bo~naga, L.V.R Tetrahedron Lett 2003, 44, 3417
1550Kim, S.-W.; Son, S.U.; Lee, S.I.; Hyeon, T.; Chung, Y.K J Am Chem Soc.2000, 122, 1550
1551Kim, S.-W.; Son, S.U.; Lee, S.S.; Hyeon, T.; Chung, Y.K Chem Commun.2001, 2212; Son, S.U.; Lee, S.I.;Chung, Y.K.; Kim, S.-W.; Hyeon, T Org Lett.2002, 4, 277
1552
Krafft, M.E.; Wright, J.A.; Llorente, V.R.; Bo~naga, L.V.R Can J Chem 2005, 83, 1006
Trang 5dendritic Co catalyst has been used.1553 Ultrasound promoted1554 and microwave promoted1555 reactions have been developed Polycyclic compounds (tricyclic and higher) are prepared in a relatively straightforward manner using this reaction.1556Asymmetric Pauson–Khand reactions are known.1557
The Pauson–Khand reaction is compatible with other groups or heteroatoms elsewhere
in the molecule These include ethers and aryl halides,1558 esters,1559 amides,1560alcohols,1561diols,1562and an indole unit.1563A silicon-tethered Pauson–Khand reaction
is known.1564Allenes are reaction partners in the Pauson–Khand reaction.1565This type
of reaction can be extended to form six-membered rings using a Ru catalyst.1566A Pauson–Khand process was reported.1567 In some cases, an aldehyde can serve as the source of the carbonyl for carbonylation.1568
OCOC
OCOCOC
1553
Dahan, A.; Portnoy, M Chem Commun.2002, 2700
1554
Ford, J.G.; Kerr, W.J.; Kirk, G.G.; Lindsay, D.M.; Middlemiss, D Synlett2000, 1415
1555Iqbal, M.; Vyse, N.; Dauvergne, J.; Evans, P Tetrahedron Lett.2002, 43, 7859
1556Ishizaki, M.; Iwahara, K.; Niimi, Y.; Satoh, H.; Hoshino, O Tetrahedron2001, 57, 2729; Son, S.U.; Yoon,Y.A.; Choi, D.S.; Park, J.K.; Kim, B.M.; Chung, Y.K Org Lett.2001, 3, 1065
1557Verdaguer, X.; Moyano, A.; Pericas, M.A.; Riera, A.; Maestro, M.A.; Mahıa, J J Am Chem Soc 2000, 122,10242l; Konya, D.; Robert, F.; Gimbert, Y.; Greene, A.E Tetrahedron Lett.2004, 45, 6975
1558Perez-Serrano, L.; Banco-Urgoiti, J.; Casarrubios, L.; Domınguez, G.; Perez-Castells, J J Org Chem 2000,
65, 3513 For a review, see Suh W.H.; Choi, M.; Lee, S.I.; Chung, Y.K Synthesis2003, 2169
1559
Krafft, M.E.; Bo~naga, L.V.R Angew Chem Int Ed 2000, 39, 3676, and references cited therein; Jeong, N.;Sung, B.S.; Choi, Y.K J Am Chem Soc.2000, 122, 6771; Sturla, S.J.; Buchwald, S.L J Org Chem 2002, 67, 3398.1560
Comely, A.C.; Gibson, S.E.; Stevenazzi, A.; Hales, N.J Tetrahedron Lett.2001, 42, 1183
1561
Blanco-Urgoiti, J.; Casarrubios, L.; Domınguez, G.; Perez-Castells, J Tetrahedron Lett 2001, 42, 3315.1562
Mukai, C.; Kim, J.S.; Sonobe, H.; Hanaoka, M J Org Chem.1999, 64, 6822
1563Perez-Serrano, L.; Domınguez, G.; Perez-Castells, J J Org Chem 2004, 69, 5413
1564
Brummond, K.M.; Sill, P.C.; Rickards, B.; Geib, S.J Tetrahedron Lett.2002, 43, 3735; Reichwein, J.F.;Iacono, S.T.; Patel, U.C.; Pagenkopf, B.L Tetrahedron Lett.2002, 43, 3739
1565
Brummond, K.M.; Chen, H.; Fisher, K.D.; Kerekes, A.D.; Rickards, B.; Sill, P.C.; Geib, A.D Org Lett.2002,
4, 1931 See Shibata, T.; Kadowaki, S.; Hirase, M.; Takagi, K Synlett2003, 573
1566
Trost, B.M.; Brown, R.E.; Toste, F.D J Am Chem Soc.2000, 122, 5877
1567Rausch, B.J.; Gleiter, R Tetrahedron Lett.2001, 42, 1651
1568See Shibata, T.; Toshida, N.; Takagi, K J Org Chem.2002, 67, 7446; Morimoto, T.; Tsutsumi, K.; Kakiuchi,
K Tetrahedron Lett.2004, 45, 9163
1569Magnus, P.; Principe, L.M Tetrahedron Lett.1985, 26, 4851
1570For a review, see Brummond, K.M.; Kent, J.L Tetrahedron2000, 56, 3263
1571Krafft, M.E Tetrahedron Lett.1988, 29, 999
1572Gimbert, Y.; Lesage, D.; Milet, A.; Fournier, F.; Greene, A.E.; Tabet, J.-C Org Lett.2003, 5, 4073 SeeRobert, F.; Milet, A.; Gimbert, Y.; Konya, D.; Greene, A.E J Am Chem Soc.2001, 123, 5396
Trang 6concluded that the LUMO of the coordinated alkene plays a crucial role in alkene reactivity by determining the degree of back-donation in the complex.1573
Other carbonylation methods are available Carbonylation occurs with conjugated ketones to give 1.4-diketones, using phenylboronic acid (see Reaction 13-12), CO and
a Rh catalyst.1574 A noncarbonylation route treated a conjugated diene with an excess
of tert-butyllithium, and quenching with CO2 led to a cyclopentadienone.1575 When quenched with CO rather than CO2, a nonconjugated cyclopentenone was formed.1576Note that a carbonylation reaction with CO, a diyne, and an Ir1577or a Co catalyst1578provided similar molecules.
With any method, if the alkene contains a functional group (e.g., OH, NH2, or CONH2), the corresponding lactone (Reaction 16-63),1579lactam (Reaction 16-74), or cyclic imide may be the product.1580Titanium,1581Pd,1582Ru,1583and Rh1584catalysts have been used
to generate lactones Allenic alcohols are converted to butenolides with 10 atm of CO and a
Ru catalyst.1585Larger ring conjugated lactones can also be formed by this route using the appropriate allenic alcohol.1586Propargylic alcohols lead to b-lactones1587or to buteno- lides with CO/H2O and a Rh catalyst.1588 Allenic tosyl-amides are converted to N-tosyl a,b-unsaturated pyrrolidinones using 20 atm of CO and a Ru catalyst.1589 Conjugated imines are converted to similar products with CO, ethylene, and a Ru catalyst.1590Propargyl alcohols generate lactones when treated with a chromium pentacarbonyl carbene complex.1591 Amines add to allenes, in the presence of CO and a Pd catalyst, to form conjugated amides.1592
The reaction of a secondary amine, CO, a terminal alkyne, and t-BuMe2SiH with a
Rh catalyst led to a conjugated amide bearing the silyl group of the C C unit.1593Reaction
of a molecule containing an amine and an alkene unit was carboxylated with CO in the presence of a Pd catalyst to give a lactam.1594 A similar reaction with a molecule containing an amine and an alkyne also generated a lactam, in the presence of CO and
1573de Bruin, T.J.M.; Milet, A.; Greene, A.E.; Gimbert, Y J Org Chem.,2004 69, 1075
1574Sauthier, M.; Castanet, Y.; Mortreux, A Chem Commun.2004 1520
1575Xi, Z.; Song, Q J Org Chem.2000, 65, 9157
1576Song, Q.; Chen, J.; Jin, X.; Xi, Z J Am Chem Soc.2001, 123, 10419; Song, Q.; Li, Z.; Chen, J.; Wang, C.;
Xi, Z Org Lett.2002, 4, 4627
1577Shibata, T.; Yamashita, K.; Katayama, E.; Takagi, K Tetrahedron2002, 58, 8661
Kablaoui, N.M.; Hicks, F.A.; Buchwald, S.L J Am Chem Soc.1997, 119, 4424
Yoneda, E.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S Tetrahedron Lett.2001, 42, 5459
1587Ma, S.; Wu, B.; Zhao, S Org Lett.2003, 5, 4429
1588Fukuta, Y.; Matsuda, I.; Itoh, K Tetrahedron Lett.2001, 42, 1301
1589Kang, S.-K.; Kim, K.-J.; Yu, C.-M.; Hwang, J.-W.; Do, Y.-K Org Lett.2001, 3, 2851
1590Chatani, N.; Kamitani, A.; Murai, S J Org Chem.2002, 67, 7014
1591Good, G.M.; Kemp, M.I.; Kerr, W.J Tetahedron Lett.2000, 41, 9323
1592Grigg, R.; Monteith, M.; Sridharan, V.; Terrier, C Tetrahedron1998, 54, 3885
1593Matsuda, I.; Takeuchi, K.; Itoh, K Tetrahedron Lett.1999, 40, 2553
1594
Okuro, K.; Kai, H.; Alper, H Tetrahedron Asymmetry1997, 8, 2307
Trang 7a Rh catalyst.1595An intramolecular carbonylation reaction of a conjugated imine, with
CO, ethylene and a Ru catalyst, led to a highly substituted b,g-unsaturated lactam.1596
or primary product.1601Alkylidenecyclopropane derivatives undergo hydroformylation to give aldehydes with a quaternary center.1602
Good yields for hydroformylation have been reported using Rh catalysts in the presence
of certain other additives.1603 Among the side reactions are the aldol Reaction ( 16-34), acetal formation, the Tischenko Reaction ( 19-82), and polymerization In one case using
a Rh catalyst, 2-octene gave nonanal, presumably via a h3-allyl complex (Sec 3.C).1604Conjugated dienes give dialdehydes when Rh catalysts are used1605 but saturated monoaldehydes (the second double bond is reduced) with cobalt carbonyls Both 1,4- and 1,5-dienes may give cyclic ketones.1606
Hydroformylation of triple bonds proceeds very slowly, and few examples have been reported.1607However, in the presence of a Rh catalyst, the triple bond of a conjugated
1595Shiba, T.; Zhou, D.-Y.; Onitsuka, K.; Takahashi, S Tetrahedron Lett.2004, 45, 3211
1596Berger, D.; Imhof, W Tetrahedron2000, 56, 2015
1597See Kalck, P.; Peres, Y.; Jenck, J Adv Organomet Chem.1991, 32, 121; Davies, J.A in Hartley, F.R.; Patai, S.The Chemistry of the Metal–Carbon Bond, Vol 3, Wiley, NY,1985, pp 361–389; Collman, J.P.; Hegedus, L.S.;Norton, J.R.; Finke, R.G Principles and Applications of Organotransition Metal Chemistry, University ScienceBooks, Mill Valley, CA1987, pp 621–632; Pino, P J Organomet Chem 1980, 200, 223; Falbe, J Carbon Monoxide
in Organic Synthesis Springer, NY,1980, pp 3–77 See Ohshiro, Y.; Hirao, T Heterocycles 1984, 22, 859.1598
See Amer, I.; Alper, H J Am Chem Soc.1990, 112, 3674; Jardine, F.H in Hartley, F.R The Chemistry of theMetal-Carbon Bond, Vol 4, Wiley, NY,1987, pp 733–818, pp 778–784
Breit, B.; Seiche, W J Am Chem Soc.2003, 125, 6608
1602Simaan, S.; Marek, I J Am Chem Soc.2010, 132, 4066
1603Johnson, J.R.; Cuny, G.D.; Buchwald, S.L Angew Chem Int Ed.1995, 34, 1760
1604van der Veen, L.A.; Kamer, P.C.J.; van Leeuwen, P.W.N.M Angew Chem Int Ed.1999, 38, 336
1605Fell, B.; Rupilius, W Tetrahedron Lett.1969, 2721
1606See Mullen, A in Falbe, J New Syntheses with Carbon Monoxide, Springer, NY,1980, pp 414–439 See also,Eilbracht, P.; H€uttmann, G.; Deussen, R Chem Ber 1990, 123, 1063, and other papers in this series
1607See Botteghi, C.; Salomon, C Tetrahedron Lett.1974, 4285 For an indirect method, see Campi, E.;Fitzmaurice, N.J.; Jackson, W.R.; Perlmutter, P.; Smallridge, A.J Synthesis1987, 1032
Trang 8enyne is formylated.1608 The Rh catalyzed reaction can be regioselective.1609 Many functional groups (e.g., OH, CHO, CO2R,1610 CN), can be present in the molecule, although halogens usually interfere Stereoselective syn addition has been reported,1611and also stereoselective anti addition.1612
Asymmetric hydroformylation of alkenes has been accomplished with a chiral catalyst,1613and in the presence of chiral additives.1614 The choice of ligand is important in such reactions.1615Cyclization to prolinal derivatives has been reported with allylic amines.1616When dicobalt octacarbonyl [Co(CO)4]2is the catalyst, the species that actually adds to the double bond is tricarbonylhydrocobalt [HCo(CO)3].1617Carbonylation [RCo(CO)3þ
CO ! RCo(CO)4] takes place followed by a rearrangement and a reduction of the C Co bond, similar to steps 4 and 5 of the nickel carbonyl mechanism shown in Reaction 15-35 The reducing agent in the reduction step is tetracarbonylhydrocobalt [HCo(CO)4],1618or, under some conditions, H2.1619 When HCo(CO)4 was the agent used to hydroformylate styrene, the observation of CIDNP (Sec 5.C.i) indicated that the mechanism is different, and involves free radicals.1620Key intermediates have been detected in the Co catalyzed hydro- formylation reaction.1621Alcohols can be obtained by allowing the reduction to continue after all the CO is used up It has been shown1622that the formation of alcohols is a second step, occurring after the formation of aldehydes, and that HCo(CO)3is the reducing agent.
The reaction is therefore a nucleophilic addition
1608van den Hoven, B.G.; Alper, H J Org Chem.1999, 64, 3964
1609Kuil, M.; Soltner, T.; van Leeuwen, P.W.N.M.; Reek, J.N.H J Am Chem Soc.2006, 128, 11344
1610See Hu, Y.; Chen, W.; Osuna, A.M.B.; Stuart, A.M.; Hope, E.G.; Xiao, J Chem Commun.2001, 725
1611See Haelg, P.; Consiglio, G.; Pino, P Helv Chim Acta1981, 64, 1865
Mirbach, M.F J Organomet Chem.1984, 265, 205 For the mechanism see Orchin, M Acc Chem Res
1981, 14, 259; Versluis, L.; Ziegler, T.; Baerends, E.J.; Ravenek, W J Am Chem Soc 1989, 111, 2018
1618Ungvary, F.; Marko, L Organometallics 1982, 1, 1120
1619See Kovacs, I.; Ungvary, F.; Marko, L Organometallics 1986, 5, 209
1620Bockman, T.M.; Garst, J.F.; King, R.B.; Marko, L.; Ungvary, F J Organomet Chem 1985, 279, 165
1621Godard, C.; Duckett, S.B.; Polas, S.; Tooze, R.; Whitwood, A.C J Am Chem Soc.2005, 127, 4994
1622Aldridge, C.L.; Jonassen, H.B J Am Chem Soc.1963, 85, 886
1623See Friedrich, K in Patai, S.; Rappoport, Z The Chemistry of Functional Groups, Supplement C pt 2, Wiley,
NY,1983, pp 1345–1390; Nagata, W.; Yoshioka, M Org React 1977, 25, 255; Brown, E.S in Wender, I.; Pino, P.Organic Syntheses via Metal Carbonyls, Vol 2, Wiley, NY,1977, pp 655–672
Trang 9and is base catalyzed Hydrogen cyanide can be added to ordinary alkenes in the presence
of dicobalt octacarbonyl1624or certain other transition metal compounds.1625When Z is COR or, more especially, CHO, 1,2-addition (Reaction 16-53) is an important competing reaction and may be the only reaction An acid-catalyzed hydrocyanation is also known.1626 Triple bonds react very well when catalyzed by an aqueous solution of CuCl, NH4Cl, and HCl or by Ni or Pd compounds.1627 The HCN can be generated
in situ from acetone cyanohydrin (see Reaction 16-52), avoiding the use of the poisonous HCN.1628Alkenes react with HCN via this procedure to give a nitrile in the presence of a Ni complex.1629
One or 2 molar equivalents of HCN can be added to a triple bond, since the initial product is a Michael-type substrate Acrylonitrile is commercially prepared this way, by the addition of HCN to acetylene Alkylaluminum cyanides (e.g., Et2AlCN), or mixtures of HCN and trialkylalanes (R3Al) are especially good reagents for conjugate addition of HCN1630to a,b-unsaturated ketones and a,b-unsaturated acyl halides An indirect method for the addition of HCN to ordinary alkenes uses an isocyanide (RNC) and Schwartz’s reagent (see Reaction 15-17); this method gives anti-Markovnikov addition.1631
tert-Butyl isocyanide and TiCl4have been used to add HCN to C CZ alkenes.1632Pretreatment with NaI/Me3SiCl followed by CuCN converts alkynes to vinyl nitriles.1633
When an alkene is treated with Me3SiCN and AgClO4, followed by aq NaHCO3, the product is the isonitrile (RNC) formed with Markovnikov selectivity.1634Enantioselective cyanation using TMSCN and HCN, and a Gd catalyst, leads to b-cyano amides.1635
OS I, 451; II, 498; III, 615; IV, 392, 393, 804; V, 239, 572; VI, 14.
For addition of ArH, see Reaction 11-12 (Friedel–Crafts alkylation).
15.C.iii Reactions in Which Hydrogen Adds to Neither Side
Some of these reactions are cycloadditions (Reactions 15-50, 15-62, 15-54, and 15-57–15-66) In such cases, addition to the multiple bond closes a ring:
See Brown, E.S in Wender, P.; Pino, P Organic Syntheses via Metal Carbonyls, Vol 2, Wiley, NY,1977,
pp 658–667; Tolman, C.A.; McKinney, R.J.; Seidel, W.C.; Druliner, J.D.; Stevens, W.R Adv Catal.1985, 33, 1.For studies of the mechanism see McKinney, R.J.; Roe, D.C J Am Chem Soc.1986, 108, 5167; Funabiki, T.;Tatsami, K.; Yoshida, S J Organomet Chem.1990, 384, 199 See also, Bini, L.; M€uller, C.; Vogt, D Chem.Commun.2010, 8325
1626
Yanagisawa, A.; Nezu, T.; Mohri, S.-i Org Lett.2009, 11, 5286
1627
Jackson, W.R.; Lovel, C.G Aust J Chem.1983, 36, 1975
1628Jackson, W.R.; Perlmutter, P Chem Br.1986, 338
1629Yan, M.; Xu, Q.-Y.; Chan, A.S.C Tetrahedron Asymmetry2000, 11, 845
1630See Nagata, W.; Yoshioka, M Org React.1977, 25, 255
1631Buchwald, S.L.; LeMaire, S.J Tetrahedron Lett.1987, 28, 295
1632Ito, Y.; Kato, H.; Imai, H.; Saegusa, T J Am Chem Soc.1982, 104, 6449
1633Luo, F.-T.; Ko, S.-L.; Chao, D.-Y Tetrahedron Lett.1997, 38, 8061
1634Kitano, Y.; Chiba, K.; Tada, M Synlett1999, 288
1635
Mita, T.; Kazuki, K.; Kanai, M.; Shibasaki, M J Am Chem Soc.2005, 127, 514
Trang 10A Halogen on One or Both Sides
15-39 Halogenation of Double and Triple Bonds (Addition of Halogen, Halogen) Dihalo-addition
Br Br+ Br2
Most double bonds are easily halogenated1636with bromine, chlorine, or inter-halogen compounds.1637Substitution can compete with addition in some cases.1638Iodination has also been accomplished, but the reaction is slower.1639 Under free radical conditions, iodination proceeds more easily.1640 However, vic-diiodides are generally unstable and tend to revert to iodine and the alkene.
X–X
XX
Under ordinary conditions fluorine itself is too reactive to give simple addition, and mixtures are obtained.1644 However, F2 has been successfully added to certain double bonds in an inert solvent at low temperatures ( 78C), usually by diluting the F
2gas with Ar or N2.1645 Addition of fluorine has also been accomplished with other reagents (e.g., p-Tol-IF2/Et3N 5 HF),1646 and a mixture of PbO2and SF4.1647 The Au catalyzed reaction of Et3N HF with alkynes gives vinyl fluorides.1648
1642See Dessau, R.M J Am Chem Soc.1979, 101, 1344
1643See Cais, M in Patai, S The Chemistry of Alkenes, Vol 1, Wiley, NY,1964, pp 993
1644See Fuller, G.; Stacey, F.W.; Tatlow, J.C.; Thomas, C.R Tetrahedron1962, 18, 123
1645Rozen, S.; Brand, M J Org Chem.1986, 51, 3607
1646Hara, S.; Nakahigashi, J.; Ishi-i, K.; Sawaguchi, M.; Sakai, H.; Fukuhara, T.; Yoneda, N Synlett1998, 495
1647Bissell, E.R.; Fields, D.B J Org Chem.1964, 29, 1591
1648
Akana, J.A.; Bhattacharyya, K.X.; M€uller, P.; Sadighi, J.P J Am Chem Soc 2007, 129, 7736
Trang 11The reaction with bromine is very rapid and is easily carried out at room ture,1649 although the reaction is reversible under some conditions.1650 In the case of bromine, an alkene Br2complex has been detected in at least one case.1651Bromine is often used as a qualitative or quantitative test for unsaturation1652because the vast majority
tempera-of double bonds can be successfully brominated Even when functions (aldehyde, ketone, amine, etc.) are present in the molecule, they do not interfere, since the reaction with double bonds is faster Bromination has been carried out in an ionic liquid.1653
Several reagents other than chlorine gas add Cl2 to double bonds, among them
Me3SiClMnO2,1654 BnNEt3MnO4/Me3SiCl,1655 and KMnO4–oxalyl chloride.1656 A convenient reagent for the addition of Br2 to a double bond on a small scale is the commercially available pyridinium bromide perbromide (C5H5NHþBr3 1657Potassium bromide with ceric ammonium nitrate, in water/dichloromethane, gives the dibromide.1658
A combination of KBr and Selectfluor also give the dibromide.1659 A combination of CuBr2in aq THF and a chiral ligand led to the dibromide with good enantioselectivity.1660Either Br2or Cl2can also be added using CuBr2or CuCl2in the presence of acetonitrile, methanol, or triphenylphosphine.1661 Alkenes are brominated using KBr and diacetox- yiodobenzene.1662 Note that theoretical and experimental studies have shown that in nonpolar solvents the bromination of acetylene via a covalent tribromide adduct is strongly favored over the textbook mechanism via a bridged bromonium ion.
Mixed halogenations have also been achieved, and the order of activity for some of the reagents is BrCl > ICl1663> Br2> IBr > I2.1664Mixtures of Br2and Cl2have been used to give bromochlorination,1665 as has tetrabutylammonium dichlorobromate (Bu4NBrCl2).1666 Iodochlorination has been achieved with KICl2,1667 CuCl2, and either
I2, HI, or CdI2; iodofluorination1668 with mixtures of AgF and I2;1669 and mixtures of N-bromo amides in anhydrous HF give bromofluorination.1670 Bromo-, iodo-, and
1649See Bellucci, G.; Chiappe, C J Org Chem.1993, 58, 7120
1650Zheng, C.Y.; Slebocka-Tilk, H.; Nagorski, R.W.; Alvarado, L.; Brown, R.S J Org Chem.1993, 58, 2122
1651Bellucci, G.; Chiappe, C.; Bianchini, R.; Lenoir, D.; Herges, R J Am Chem Soc.1995, 117, 12001
1652See Kuchar, E.J in Patai, S The Chemistry of Alkenes, Vol 1, Wiley, NY,1964, pp 273–280
1653Chiappe, C.; Capraro, D.; Conte, V.; Picraccini, D Org Lett.2001, 3, 1061
1654Bellesia, F.; Ghelfi, F.; Pagnoni, U.M.; Pinetti, A J Chem Res (S)1989, 108, 360
1655Marko, I.E.; Richardson, P.R.; Bailey, M.; Maguire, A.R.; Coughlan, N Tetrahedron Lett 1997, 38, 2339.1656
Marko, I.E.; Richardson, P.F Tetrahedron Lett 1991, 32, 1831
1657
Fieser, L.F.; Fieser, M Reagents for Organic Synthesis Vol 1, Wiley, NY,1967, pp 967–970 For a discussion
of the mechanism, see Bellucci, G.; Bianchini, R.; Vecchiani, S J Org Chem.1986, 51, 4224
White, E.P.; Robertson, P.W J Chem Soc.1939, 1509
1665Buckles, R.E.; Forrester, J.L.; Burham, R.L.; McGee, T.W J Org Chem.1960, 25, 24
1666Negoro, T.; Ikeda, Y Bull Chem Soc Jpn.1986, 59, 3519
1667Zefirov, N.S.; Sereda, G.A.; Sosounk, S.E.; Zyk, N.V.; Likhomanova, T.I Synthesis1995, 1359
1668See Sharts, C.M.; Sheppard, W.A Org React.1974, 21, 125, see pp 137–157; Boguslavskaya L.S Russ.Chem Rev.1984, 53, 1178
1669Evans, R.D.; Schauble, J.H Synthesis1987, 551; Kuroboshi, M.; Hiyama, T Synlett 1991, 185
1670Pattison, F.L.M.; Peters, D.A.V.; Dean, F.H Can J Chem 1965, 43, 1689 For other methods, seeShimizu, M.; Nakahara, Y.; Yoshioka, H J Chem Soc., Chem Commun.1989, 1881
Trang 12chlorofluorination have also been achieved by treatment of the substrate with a solution of
Br2, I2, or an N-halo amide in polyhydrogen fluoride–pyridine;1671while addition of I along with Br, Cl, or F has been accomplished with the reagent bis(pyridine)iodo(I) tetrafluor- oborate [I(Py)2BF4] and Br, Cl, or F, respectively.1672 This reaction, which is also successful for triple bonds,1673can be extended to addition of I and other nucleophiles (e.g., NCO, OH, OAc, and NO2).1673
Conjugated systems give both 1,2- and 1,4-addition.1644 Triple bonds add bromine, although generally more slowly than double bonds (see Sec 15.B.i) Molecules that contain both double and triple bonds are preferentially attacked at the double bond Addition of 2 molar equivalents of bromine to triple bonds gives tetrabromo products There is evidence that the addition of the first molar equivalent of bromine to a triple bond may take place by a nucleophilic mechanism.1674 Molecular diiodine on Al2O3adds to triple bonds to give good yields of 1,2-diiodoalkenes.1675Interestingly, 1,1-diiodo alkenes are prepared from an alkynyltin compound, via initial treatment with Cp2Zr(H)Cl, and then 2.15 equiv of iodine.1676A mixture of NaBO3and NaBr adds two bromine atoms across a triple bond.1677With allenes it is easy to stop the reaction after only 1 equiv has added, to give X CCX C.1678Addition of halogen to ketenes gives a-halo acyl halides, but the yields are not good.
OS I, 205, 521; II, 171, 177, 270, 408; III, 105, 123, 127, 209, 350, 526, 531, 731, 785; IV,
130, 195, 748, 851, 969; V, 136, 370, 403, 467; VI, 210, 422, 675, 862, 954; IX, 117; 76, 159 15-40 Addition of Hypohalous Acids and Hypohalites
(Addition of Halogen, Oxygen)
Hydroxy-chloro-addition, and so on.1679
Hypohalous acids (HOCl, HOBr, and HOI) react with alkenes1680to produce drins.1681Both HOBr and HOCl can be generated in situ by the reaction between water and
halohy-Br2or Cl2, respectively The compound HOI, generated from I2and H2O, also adds to
1671
Nojima, M.; Kerekes, I.; Olah, J.A J Org Chem.1979, 44, 3872 See Camps, F.; Chamorro, E.; Gasol, V.;Guerrero, A J Org Chem.1989, 54, 4294; Ichihara, J.; Funabiki, K.; Hanafusa, T Tetrahedron Lett 1990, 31,3167
1672Barluenga, J.; Gonzalez, J.M.; Campos, P.J.; Asensio, G Angew Chem Int Ed 1985, 24, 319.1673
Barluenga, J.; Rodrıguez, M.A.; Gonzalez, J.M.; Campos, P.J.; Asensio, G Tetrahedron Lett 1986, 27, 3303.1674
Sinn, H.; Hopperdietzel, S.; Sauermann, D Monatsh Chem.1965, 96, 1036
1675Hondrogiannis, G.; Lee, L.C.; Kabalka, G.W.; Pagni, R.M Tetrahedron Lett.1989, 30, 2069
1676Dabdoub, M.J.; Dabdoub, V.B.; Baroni, A.C.M J Am Chem Soc.2001, 123, 9694
1677Kabalka, G.W.; Yang, K Synth Commun.1998, 28, 3807; Kabalka, G.W.; Yang, K.; Reddy, N.K.; Narayana,
A Synth Commun.1998, 28, 925
1678See Jacobs, T.L in Landor, S.R The Chemistry of Allenes, Vol 2, Acaademic Press, NY,1982, pp 466–483
1679Addends are listed in order of priority in the Cahn–Ingold–Prelog system (Sec 4.E.i)
1680Larock, R.C Comprehensive Organic Transformations, 2nd ed., Wiley–VCH, NY,1999, pp 638–642.1681
See Boguslavskaya, L.S Russ Chem Rev.1972, 41, 740
Trang 13double bonds, if the reaction is carried out in tetramethylene sulfone–CHCl31682or if an oxidizing agent (e.g., HIO3) is present.1683 Iodine and cerium sulfate in aq acetonitrile generates iodohydrins,1684as do iodine and ammonium acetate in acetic acid,1685or NaIO4with sodium bisulfite.1686
The HOBr can also be conveniently added by the use of a reagent consisting of an bromo amide (e.g., NBS or N-bromoacetamide) and a small amount of water in a solvent (e.g., DMSO or dioxane).1687 N-Iodosuccinimide in aq dimethoxyethane leads to the iodohydrin.1688 An especially powerful reagent for HOCl addition is tert-butyl hydro- peroxide (or di-tert-butyl peroxide) along with TiCl4.1689 Chlorohydrins can be conve- niently prepared by treatment of the alkene with Chloramine T (TsNCl Naþ)1690 in acetone–water.1691The compound HOI can be added by treatment of alkenes with periodic acid and NaHSO3.1692 There are Se catalyzed iodohydrin forming reactions.1693 The reaction of an alkene with polymeric (SnO)n, and then HCl with Me3SiOOSiMe3, leads
N-to the chlorohydrin.1694 Hypervalent iodine compounds react with an alkene and iodine
in aqueous media to give the iodohydrin.1695Halohydrins are produced in ionic liquids.1696N-Bromo and N-iodosaccharin have been used to prepare the corresponding halohydrins.1697The compound HOF has also been added, but this reagent is difficult to prepare in a pure state and explosions have occurred.1698
The mechanism of HOX addition is electrophilic, with initial attack by the alkene on the positive halogen end of the HOX dipole Following Markovnikov’s rule, the positive halogen goes to the side of the double bond that has more hydrogen atoms (forming a more stable carbocation) This carbocation (or bromonium or iodonium ion in the absence of an aqueous solvent) reacts withOH or H
2O to give the product If the substrate is treated with Br2or Cl2(or another source of positive halogen, e.g., NBS) in an alcohol or a carboxylic acid solvent, it
is possible to obtain, directly C CCOR or XCCOCOR, respectively (see also, Reaction 15-48).1699Even the weak nucleophile CF3SO2Ocan participate in the second step The addition of Cl2or Br2to alkenes in the presence of this ion resulted in the formation
of some b-haloalkyl triflates.1700There is evidence that the mechanism with Cl2and H2O is
1682Cambie, R.C.; Noall, W.I.; Potter, G.J.; Rutledge, P.S.; Woodgate, P.D J Chem Soc Perkin Trans 1,1977, 266
1683See Antonioletti, R.; D’Auria, M.; De Mico, A.; Piancatelli, G.; Scettri, A Tetrahedron1983, 39, 1765
1684Horiuchi, C.A.; Ikeda, A.; Kanamori, M.; Hosokawa, H.; Sugiyama, T.; Takahashi, T.T J Chem Res (S)
Carrera, I.; Brovetto, M.C.; Seoane, G.A Tetrahedron Lett.2006, 47, 7849
1694Sakurada, I.; Yamasaki, S.; G€ottlich, R.; Iida, T.; Kanai, M.; Shibasaki, M J Am Chem Soc 2000, 122, 1245
1695DeCorso, A.R.; Panunzi, B.; Tingoli, M Tetrahedron Lett.2001, 42, 7245
1696Yadav, J.S.; Reddy, B.V.S.; Baishya, G.; Harshavardhan, S.J.; Chary, Ch.J.; Gupta, M.K Tetrahedron Lett
2005, 46, 3569
1697Urankar, D.; Rutar, I.; Modec, B.; Dolenc, D Eur J Org Chem.2005, 2349
1698Migliorese, K.G.; Appelman, E.H.; Tsangaris, M.N J Org Chem.1979, 44, 1711
1699Larock, R.C Comprehensive Organic Transformations, 2nd ed., Wiley–VCH, NY,1999, pp 642–643.1700
Zefirov, N.S.; Koz’min, A.S Acc Chem Res.1985, 18, 154; Sov Sci Rev Sect B 1985, 7, 297
Trang 14different from that with HOCl.1701Both HOCl and HOBr can be added to triple bonds to give dihalo carbonyl compounds ( CX2CO).
Alcohols and halogens react with alkenes to form halo ethers When a homoallylic alcohol is treated with bromine, cyclization occurs to give a 3-bromotetrahydrofuran derivative.1702tert-Butyl hypochlorite (Me3COCl), hypobromite, and hypoiodite1703add
to double bonds to give halogenated tert-butyl ethers (X CCOCMe3) This is a convenient method for the preparation of tertiary ethers Iodine and ethanol convert some alkenes to iodo-ethers.1704Iodine, alcohol, and a Ce(OTf)2catalyst also generates the iodo- ether.1705When Me3COCl or Me3COBr is added to alkenes in the presence of excess ROH, the ether X CCOR is produced.1706
Vinylic ethers give b-halo acetals.1707
Chlorine acetate [solutions of which are prepared by treating Cl2with Hg(OAc)2in an appropriate solvent] adds to alkenes to give acetoxy chlorides.1708 Acetoxy fluorides have been obtained by treatment of alkenes with CH3COOF.1709
For a method of iodoacetyl addition, see Reaction 15-48.
OS I, 158; IV, 130, 157; VI, 184, 361, 560; VII, 164; VIII, 5, 9.
15-41 Halolactonization and Halolactamization
Halo-alkoxylation
Halo esters can be formed by addition of halogen atoms and ester groups to an alkene Alkene carboxylic acids give a tandem reaction of formation of a halonium ion followed by intramolecular displacement of the carboxylic group to give a halo lactone This tandem addition of X and OCOR is called halolactonization.1710
CO2H
OO1.5 I2 , AcOH , 120 °C
I
The most common version of this reaction is known as iodolactonization,1711and a typical example is the conversion of 111 to 112.1712Bromo lactones and, to a lesser extent, chloro lactones have also been prepared In general, addition of the halogen to an alkenyl acid, as shown, leads to the halo-lactone Other reagents include Iþ(collidine)2PF6,1713KI/sodium1701
Buss, E.; Rockstuhl, A.; Schnurpfeil, D J Prakt Chem.1982, 324, 197
1709Rozen, S.; Lerman, O.; Kol, M.; Hebel, D J Org Chem.1985, 50, 4753
1710See Cardillo, G.; Orena, M Tetrahedron1990, 46, 3321; Dowle, M.D.; Davies, D.I Chem Soc Rev 1979, 8,
171 For a list of reagents that accomplish this, with references, see Larock, R.C Comprehensive OrganicTransformations, 2nd ed., Wiley–VCH, NY,1999, pp 1870–1876 Also see Bartlett, P.A in Morrison, J.D.Organic Synthesis Vol 3, Wiley, NY,1984, pp 411–454, 416–425
1711Corey, E.J.; Albonico, S.M.; Koelliker, V.; Schaaf, T.K.; Varma, R.K J Am Chem Soc.1971, 93, 1491
1712Yaguchi, Y.; Akiba, M.; Harada, M.; Kato, T Heterocycles1996, 43, 601
1713
Homsi, F.; Rousseau, G J Org Chem.1998, 63, 5255
Trang 15persulfate.1714The Tl1715and Y1716 reagents, along with the halogen, have also been used An enantioselective 5-endo-halolactonization procedure has been reported using systems, such as iodobis(collidine) hexafluorophosphate or AgSbF6, followed by iodine.1717 When done in the presence of a chiral Ti reagent, I2, and CuO, lactones are formed with good enantioselectivity.1718Iodine monochloride (ICl) has been used, with formation of a quaternary center at the oxygen-bearing carbon of the lactone.1719Organocatalysts have also been used to mediate asymmetric halolactonization reactions.1720Enantioselective iodolactonization occurs with pentenoic acid derivatives
in the presence of a chiral Co(salen) complex.1721
In the case of g,d-unsaturated acids, five-membered rings (g-lactones) are predominantly formed (as shown above; note that Markovnikov’s rule is followed), but six-membered and even four-membered lactones have also been made by this procedure There is a gem- dimethyl effect that favors formation of 7–11 membered ring lactones by this procedure.1722
1 Me3SiOTf , NEt3
2 I2 , THF
3 aq Na2SO3
114 113
Formation of halo-lactams (Reaction 15-43) by a procedure similar to halolactonization is difficult, but the problems have been overcome Formation of a triflate from 113 followed
by treatment with iodine leads to the iodolactam ( 114).1723 A related cyclization of N-sulfonyl-amino alkenes and NBS gave the bromo-lactam,1724 and a dichloro-N,N-bis (allylamide) was converted to a dichloro-lactam with FeCl2.1725 Note that lactone formation is possible from unsaturated amides
1721Ning, Z.; Jin, R.; Ding, J.; Gao, L Synlett2009, 2291
1722Simonot, B.; Rousseau, G Tetrahedron Lett.1993, 34, 4527
1723Knapp, S.; Rodriques, K.E Tetrahedron Lett.1985, 26, 1803
1724Tamaru, Y.; Kawamura, S.; Tanaka, K.; Yoshida, Z Tetrahedron Lett.1984, 25, 1063
1725Tseng, C.K.; Teach, E.G.; Simons, R.W Synth Commun.1984, 14, 1027
1726When a general group (e.g., halo) is used, its priority is that of the lowest member of its group (see Ref 1680).Thus the general name for this transformation is halo-alkylsulfonyl addition because “halo” has the same priority
as “fluoro”, its lowest member
Trang 16Sulfonyl halides add to double bonds to give b-halo sulfones, in the presence of free radical initiators or UV light A particularly good catalyst is cuprous chloride.1727In the presence of TsCl, AIBN and a Ru catalyst, b-chloro sulfones are generated from alkenes.1728 A combination of the anion ArSO2Na, NaI, and ceric ammonium nitrate converts alkenes to vinyl sulfones.1729 Triple bonds behave similarly, to give b-halo- a,b-unsaturated sulfones.1730In a similar reaction, sulfenyl chlorides, (RSCl) give b-halo thioethers.1731 The latter may be free radical or electrophilic additions, depending on conditions The addition of MeS and Cl has also been accomplished by treating the alkene with Me3SiCl and Me2SO.1732The use of Me3SiBr and Me2SO does not give this result; dibromides (Reaction 15-39) are formed instead.
b-Iodothiocyanates can be prepared from alkenes by treatment with I2 and cyanatotributylstannane (Bu3SnNCS).1733Bromothiocyanation can be accomplished with
isothio-Br2and thallium(I) thiocyanate.1734Lead(II) thiocyanate reacts with terminal alkynes in the presence of PhICl2 to give the bis(thiocyanato) alkene [ArC(SCN) CHSCN].1735
Such compounds were also prepared from alkenes using KSCN and FeCl31736or iodine thiocyanate.1737 b-Halo disulfides, formed by addition of arenethiosulfenyl chlorides to double-bond compounds, are easily converted to thiiranes by treatment with sodium amide
or sodium sulfide.1738
OS VIII, 212 See also, OS VII, 251.
15-43 Addition of Halogen and a Nitrogen Group (Addition of Halogen, Nitrogen) Dialkylamino-chloro-addition
H2SO4HOAc
+The groups R2N and Cl can be added directly to alkenes, allenes, conjugated dienes, and alkynes, by treatment with dialkyl-N-chloroamines and acids.1739 N-Halo amides (RCONHX) add RCONH and X to double bonds under the influence of UV light or chromous chloride.1740N-Bromoamides add to alkenes in the presence of a transition metal
1727Sinnreich, J.; Asscher, M J Chem Soc Perkin Trans 1,1972, 1543
1728Quebatte, L.; Thommes, K.; Severin, K J Am Chem Soc.2006, 128, 7440
Cambie, R.C.; Larsen, D.S.; Rutledge, P.S.; Woodgate, P.D J Chem Soc Perkin Trans 1,1981, 58.1735
Prakash, O.; Sharma, V.; Batra, H.; Moriarty, R.M Tetrahedron Lett.2001, 42, 553
1736
Yadav, J.S.; Reddy, B.V.S.; Gupta, M.K Synthesis2004, 1983
1737For a discsssion of substituent effects, see Brammer, C.N.; Nelson, D.J.; Li, R Tetrahedron Lett.2007, 48,3237
1738Fujisawa, T.; Kobori, T Chem Lett.1972, 935; Capozzi, F.; Capozzi, G.; Menichetti, S Tetrahedron Lett
Trang 17catalyst (e.g., SnCl4) to give the corresponding b-bromo amide.1741 The reaction of TsNCl2 and a ZnCl2 catalyst gave the chloro tosylamine.1742 Aminochlorination of alkenes occurs in a CO2promoted reaction with Chloramine-T (TolSO2NCl).1743
These are free radical additions, with initial attack by the R2NHþ radical ion.1744
Amines add to allenes in the presence of a Pd catalyst.1745A mixture of N-(2-nosyl)NCl2and sodium N-(2-nosyl)NHwith a CuOTf catalyst reacted with conjugated esters to give the vicinal (E)-3-chloro-2-amino ester.1746A variation of this latter reaction was done in an ionic liquid.1747
15-44 Addition of NOX and NO2X (Addition of Halogen, Nitrogen)
Nitroso-chloro-addition
NO–Cl
Cl N=O+
There are three possible products when NOCl is added to alkenes, a b-halo nitroso compound, an oxime, or a b-halo nitro compound.1748 The initial product is always the b-halo nitroso compound,1749 but these are stable only if the carbon bearing the nitrogen has no hydrogen If it has, the nitroso compound tautomerizes to the oxime,
H CN O ! C NOH With some alkenes, the initial b-halo nitroso compound is oxidized by the NOCl to a b-halo nitro compound.1750 Many functional groups may be present without interference (e.g., CO2H, CO2R, CN, OR) The mechanism in most cases is probably simple electrophilic addition, and the addition is usually anti, although syn addition has been reported in some cases.1751Markovnikov’s rule is followed, the positive
NO going to the carbon that has more hydrogen atoms.
Nitryl chloride (NO2Cl) also adds to alkenes, to give b-halo nitro compounds, but this is
a free radical process The NO2goes to the less-substituted carbon.1752Nitryl chloride also adds to triple bonds to give the expected 1-nitro-2-chloro alkenes.1753 The compound FNO2can be added to alkenes1754by treatment with HF in HNO31755or by addition of the alkene to a solution of nitronium tetrafluoroborate (NO2þBF4; see Reaction 11-2) in 70% polyhydrogen fluoride–pyridine solution1756(see also, Reaction 15-37).
See Chow, Y.L.; Danen, W.C.; Nelson, S.F.; Rosenblatt, D.H Chem Rev.1978, 78, 243
1745Besson, L.; Gore, J.; Cazes, B Tetrahedron Lett 1995, 36, 3857
See Kadzyauskas, P.P.; Zefirov, N.S Russ Chem Rev.1968, 37, 543
1749See Gowenlock, B.G.; Richter-Addo, G.B Chem Rev.2004, 104, 3315
1750Shvekhgeimer, G.A.; Smirnyagin, V.A.; Sadykov, R.A.; Novikov, S.S Russ Chem Rev.1968, 37, 351
1751See Meinwald, J.; Meinwald, Y.C.; Baker, III, T.N J Am Chem Soc.1964, 86, 4074
1752Shechter, H Rec Chem Prog.,1964, 25, 55–76
1753Schlubach, H.H.; Braun, A Liebigs Ann Chem.1959, 627, 28
1754Sharts, C.M.; Sheppard, W.A Org React.1974, 21, 125–406, see pp 236–243
1755Knunyants, I.L.; German, L.S.; Rozhkov, I.N Bull Acad Sci USSR Div Chem Sci.1963, 1794.1756
Olah, G.A.; Nojima, M Synthesis1973, 785
Trang 1815-45 Addition of XN3(Addition of Halogen, Nitrogen)
Azido-iodo-addition
I–N3
I N3+
The addition of iodine azide to double bonds gives b-iodo azides.1757The reagent can be prepared in situ from KI NaN3in the presence of Oxone–wet alumina.1758The addition is stereospecific and anti, suggesting that the mechanism involves a cyclic iodonium ion intermediate.1759 The reaction has been performed on many double-bond compounds, including allenes1760 and a,b-unsaturated ketones Similar reactions can be performed with BrN31761and ClN3 1,4-Addition has been found with acyclic conjugated dienes.1762
In the case of BrN3, both electrophilic and free radical mechanisms are important,1763while with ClN3the additions are chiefly free radical.1764Iodine monoazide (IN3) also adds
to triple bonds to give b-iodo-a,b-unsaturated azides.1765
OS VI, 893.
15-46 Addition of Alkyl Halides (Addition of Halogen, Carbon)
Alkyl-halo-addition1135
AlCl3R–X
1758
Curini, M.; Epifano, F.; Marcotullio, M.C.; Rosati, O Tetrahedron Lett.2002, 43, 1201
1759
See, however, Cambie, R.C.; Hayward, R.C.; Rutledge, P.S.; Smith-Palmer, T.; Swedlund, B.E.; Woodgate, P
D J Chem Soc Perkin Trans 1,1979, 180
1760
Hassner, A.; Keogh, J J Org Chem.1986, 51, 2767
1761
Olah, G.A.; Wang, Q.; Li, X.; Prakash, G.K.S Synlett1990, 487
1762Hassner, A.; Keogh, J Tetrahedron Lett.1975, 1575
1763Hassner, A.; Teeter, J.S J Org Chem.1971, 36, 2176
1764See Cambie, R.C.; Jurlina, J.L.; Rutledge, P.S.; Swedlund, B.E.; Woodgate, P.D J Chem Soc Perkin Trans
1,1982, 327 Also see Hassner, A Intra-Sci Chem Rep., 1970, 4, 109
1765Hassner, A.; Isbister, R.J.; Friederang, A Tetrahedron Lett.1969, 2939
1766Hassner, A.; Matthews, G.J.; Fowler, F.W J Am Chem Soc.1969, 91, 5046
1767Levy, A.B.; Brown, H.C J Am Chem Soc.1973, 95, 4067
1768
Ali, S.I.; Nikalje, M.D.; Sudalai, A Org Lett.1999, 1, 705
Trang 19Alkyl halides can be added to alkenes in the presence of a Friedel–Crafts catalyst, most often AlCl3.1769 The yields are best for tertiary R Secondary R can also be used, but primary R give rearrangement products (as with Reaction 11-11) The reactive species is the carbocation formed from the alkyl halide and the catalyst (see Reaction 11-11).1770The reaction with an alkene follows Markovnikov’s rule, and generates the more stable carbocation from the alkene after reaction with the carbocation Methyl and ethyl halides, which cannot rearrange to a more stable secondary or tertiary carbocation, give no reaction
at all Substitution is a side reaction, arising from loss of hydrogen from the carbocation ( 117) Conjugated dienes give 1,4-addition.1771
Triple bonds also undergo the reaction, to give vinylic halides.1772
substitution
additionH
R
HRX
CH2
CH2CX3RHC
a-Iodolactones add to alkenes in the presence of BEt3/O2to give the addition product.1778Other a-iodoesters add under similar conditions to give the lactone.1779Iodoesters also add
to alkenes in the presence of BEt3to give iodo-esters that have not cyclized.1780
A variant of the free radical addition method has been used for ring closure (see Reaction 15-30).
For another method of adding R and I to a triple bond, see Reaction 15-23.
OS II, 312; IV, 727; V, 1076; VI, 21; VII, 290.
1776Simal, F.; Wlodarczak, L.; Demonceau, A.; Noels, A.F Eur J Org Chem.2001, 2689
1777For a review with respect to fluoroalkenes, see Paleta, O Fluorine Chem Rev.1977, 8, 39
1778Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima, K Synlett1998, 1351
1779Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima, K J Org Chem.1998, 63, 8604
1780
Baciocchi, E.; Muraglia, E Tetrahedron Lett.1994, 35, 2763
Trang 2015-47 Addition of Acyl Halides (Addition of Halogen, Carbon)
Acyl-halo-addition
AlCl3 Cl+
Cl
OR
OR
Acyl halides add to many alkenes using Friedel–Crafts catalysts, although zation is a problem The reaction has been applied to straight-chain, branched, and cyclic alkenes, but to very few containing functional groups, other than halogen.1781 The mechanism is similar to that of Reaction 15-46, and, as in that case, substitution competes (Reaction 12-16) Increasing temperature favors substitution,1782 but good yields of addition products can be achieved if the temperature is kept under 0C The reaction usually fails with conjugated dienes, since polymerization predominates.1783Iodo acetates have been formed from alkenes using iodine and Pb(OAc)2in acetic acid.1784Rhodium- catalyzed variations are known.1785 The reaction can be performed on triple-bond compounds, producing compounds of the form RCO C CCl.1786 A formyl group and a halogen can be added to triple bonds by treatment with N,N-disubstituted formamides and POCl3(Vilsmeier conditions, Reaction 11-18).1787Chloroformates add to allenes in the presence of a Rh catalyst to give a b-chloro, b,g-unsaturated ester.1788
polymeri-OS IV, 186; VI, 883; VIII, 254.
B Oxygen, Nitrogen, or Sulfur on One or Both Sides
15-48 Dihydroxylation and Dialkoxylation (Addition of Oxygen, Oxygen)
Dihydroxy-addition, Dialkoxy-addition
HO OH
There are many reagents that add two OH groups to a double bond tion).1789The most common are OsO4,1790first used by Criegee in 1936,1791and alkaline KMnO4.1792Both give syn addition from the less-hindered side of the double bond Less
See Hudlicky, M Oxidations in Organic Chemistry American Chemical Society, Washington, 1990,
pp 67–73; Haines, A.H Methods for the Oxidation of Organic Compounds Academic Press, NY, 1985,
pp 73–98, 278–294; Sheldon, R.A.; Kochi, J.K Metal-Catalyzed Oxidations of Organic Compounds AcademicPress, NY,1981, pp 162–171, 294–296 For a list of reagents, with references, see Larock, R.C ComprehensiveOrganic Transformations, 2nd ed., Wiley–VCH, NY,1999, pp 996–1003
1790See Schr€oder, M Chem Rev 1980, 80, 187 Also see, Norrby, P.-O.; Gable, K.P J Chem Soc Perkin Trans 2,
1996, 171; Lohray, B.B.; Bhushan, V Tetrahedron Lett 1992, 33, 5113
1791Criegee, R Liebigs Ann Chem.1936, 522, 75
1792
See Fatiadi, A.J Synthesis1987, 85; Nelson, D.J.; Henley, R.L Tetrahedron Lett 1995, 36, 6375
Trang 21substituted double bonds are oxidized more rapidly than more substituted alkenes.1793Permanganate adds to alkenes to form an intermediate manganate ester (Reaction 118), which is decomposed under alkaline conditions Transition state structures and the energetics of the permanganate oxidation of alkenes has been studied using molecular mechanics.1794 Bases catalyze the decomposition of 118 by coordinating with the ester Note that there are alternative Mn complexes that may be used for cis-dihydroxylation of alkenes.1795Osmium tetroxide adds rather slowly but almost quantitatively to form a cyclic osmate ester (e.g., 119) as an intermediate,1796
which may be isolated in some cases, but is usually decomposed in solution with sodium sulfite (Na2SO3) in ethanol or other reagents.1797
119 118
O
OsOO
MnO
O O
O O
The chief drawbacks to the use of OsO4are the facts that it is expensive and toxic, but the reaction is made catalytic in OsO4 by using N-methylmorpholine-N-oxide (NMO),1798 tert-butyl hydroperoxide in alkaline solution,1799 H2O2,1800 peroxya- cid,1801 K3Fe(CN)6,1802 and non-heme iron catalysts.1803 Polymer-bound OsO4,1804and encapsulated OsO4 have been shown to give the diol in the presence of NMO,1805 as well as OsO4 on an ion exchange resin.1806
Dihydroxylation has also been reported in ionic liquids.1807 Other metals have been used to catalyze dihydroxylation, including Fe1808or Ru catalyzed1809reactions with H2O2 A catalytic amount of K2OsO4 with a Cinchona alkaloid on a ordered inorganic support, in the presence of K3Fe(CN)6, gives the cis-diol.1810
1793Crispino, G.A.; Jeong, K.-S.; Kolb, H.C.; Wang, Z.-M.; Xu, D.; Sharpless, K.B J Org Chem.1993, 58, 3785
1794Wiberg, K.B.; Wang, Y.-g.; Sklenak, S.; Deutsch, C.; Trucks, G J Am Chem Soc.2006, 128, 11537
1795de Boer, J.W.; Brinksma, J.; Browne, W.R.; Meetsma, A.; Alsters, P.L.; Hage, R.; Feringa, B.L J Am Chem.Soc.2005, 127, 7990
1796See Jørgensen, K.A.; Hoffmann, R J Am Chem Soc.1986, 108, 1867
See Usui, Y.; Sato, K.; Tanaka, M Angew Chem Int Ed.2003, 42, 5623
1801Bergstad, K.; Piet, J.J.N.; B€ackvall, J.-E J Org Chem 1999, 64, 2545
1802
Torii, S.; Liu, P.; Tanaka, H Chem Lett.1995, 319; Soderquist, J.A.; Rane, A.M.; Lopez, C.J TetrahedronLett.1993, 34, 1893 See Corey, E.J.; Noe, M.C.; Grogan, M.J Tetrahedron Lett 1994, 35, 6427; Imada, Y.; Saito,T.; Kawakami, T.; Murahashi, S.-I Tetrahedron Lett.1992, 33, 5081 for oxidation using an asymmetric ligand.1803
Chen, K.; Costas, M.; Kim, J.; Tipton, A.K.; Que, Jr., L J Am Chem Soc.2002, 124, 3026
1804Ley, S.V.; Ramarao, C.; Lee, A.-L.; Ostergaard, N.; Smith, S.C.; Shirley, I.M Org Lett.2003, 5, 185
1805Nagayama, S.; Endo, M.; Kobayashi, S J Org Chem.1998, 63, 6094
1806Choudary, B.M.; Chowdari, N.S.; Jyothi, K.; Kantam, M.L J Am Chem Soc.2002, 124, 5341
1807Closson, A.; Johansson, M.; B€ackvall, J.-E Chem Commun 2004, 1494; Branco, L.C.; Serbanovic, A.; daPonte, M.N.; Afonso, C.A.M Chem Commun.2005, 107
1808Oldenburg, P.D.; Shteinman, A.A.; Que, Jr., L J Am Chem Soc.2005, 127, 15672
1809Yip, W.-P.; Ho, C.-M.; Zhu, N.; Lau, T.-C.; Che, C.-M Chemistry: Asian J.2008, 3, 70
1810
Motorina, I.; Crudden, C.M Org Lett.2001, 3, 2325
Trang 22The end product of the reaction is a 1,2-diol Potassium permanganate is a strong oxidizing agent and can oxidize the glycol product1811(see Reaction 19-7 and 19-10) In acidic and neutral solution, it always does so; hence glycols must be prepared with alkaline1812 permanganate, but the conditions must be mild Even so, yields are seldom
>50%, although they can be improved with phase-transfer catalysis1813 or increased stirring.1814 The use of ultrasound with permanganate has resulted in good yields of the diol.1815This reaction is the basis of the Baeyer test for the presence of double bonds The oxidation is compatible with a number of functional groups, including trichloroacetamides.1816
Anti-hydroxylation can be achieved by treatment with H2O2and formic acid In this case, epoxidation (Reaction 15-50) occurs first, followed by an SN2 reaction, which results
in overall anti addition:
H+ H2O2
The same result can be achieved in one step with m-chloroperoxybenzoic acid and water.1817 Overall anti addition can also be achieved by the method of Pr evost (the Prevost reaction) In this method, the alkene is treated with iodine and silver benzoate in a 1:2 molar ratio The initial addition is anti and results in a b-halo benzoate, as shown These can be isolated, and this represents a method of addition of IOCOPh However, under normal reaction conditions, the iodine is replaced by a second PhCOO group This is a nucleophilic substitution reaction via the neighboring-group mechanism (Sec 10.C), so the groups are still anti:
I2PhCOOAg
IOCOPh
PhOCO
OCOPh
HOOH
Hydrolysis of the ester does not change the configuration The Woodward modification of the Prevost reaction is similar, but results in overall syn hydroxylation.1818
In this procedure, the alkene is treated with iodine and silver acetate in a 1:1 molar ratio in acetic acid containing water Here again, the initial product is a b-halo ester; the addition is anti and a nucleophilic replacement of the iodine occurs However, in the presence of water, neighboring-group participation is prevented or greatly decreased by solvation of the ester function, and the mechanism is the normal SN2 process,1819so the monoacetate is syn and
1811
See Wolfe, S.; Ingold, C.F.; Lemieux, R.U J Am Chem Soc.1981, 103, 938; Wolfe, S.; Ingold, C.F J Am.Chem Soc.1981, 103, 940 Also see, Lohray, B.B.; Bhushan, V.; Kumar, R.K J Org Chem 1994, 59, 1375.1812
See Taylor, J.E.; Green, R Can J Chem.1985, 63, 2777
1813
See Ogino, T.; Mochizuki, K Chem Lett.1979, 443
1814Taylor, J.E.; Williams, D.; Edwards, K.; Otonnaa, D.; Samanich, D Can J Chem.1984, 62, 11; Taylor, J.E.Can J Chem.1984, 62, 2641
1815Varma, R.S.; Naicker, K.P Tetrahedron Lett.1998, 39, 7463
1816Donohoe, T.J.; Blades, K.; Moore, P.R.; Waring, M.J.; Winter, J.J.G.; Helliwell, M.; Newcombe, N.J.; Stemp,
G J Org Chem.2002, 67, 7946
1817Fringuelli, F.; Germani, R.; Pizzo, F.; Savelli, G Synth Commun.1989, 19, 1939
1818See Brimble, M.A.; Nairn, M.R J Org Chem.1996, 61, 4801
1819
For another possible mechanism: Woodward, R.B.; Brutcher, Jr., F.V J Am Chem Soc.1958, 80, 209
Trang 23hydrolysis gives the diol as the product, with overall syn addition Although the Woodward method results in overall syn addition, the product may be different from that with OsO4or KMnO4, since the overall syn process is from the more hindered side of the alkene.1820Both the Pr evost and the Woodward methods1821 have been carried out in high yields with thallium(I) acetate and thallium(I) benzoate instead of the silver carboxylates.1822Note that cyclic sulfates can be prepared from alkenes by reaction with PhIO and
SO3 DMF.1823Diacetates have been prepared from alkenes using a Cu catalyzed reaction with PhI(OAc)2as the oxidizing agent.1824A similar Pd/Cu catalyzed reaction is known using O2as the oxidant.1825
OH
OMe
OMeOH
OMe
OMeOH
121 or 122, derivatives of the naturally occurring quinine and quinuclidine),1830along with OsO4, in what is called
N
Et H
HArOHO
Zhang, Y.; Sigman, M.S J Am Chem Soc.2007, 129, 3076
1827For diastereoselective, but not enantioselective, addition of OsO4, see Vedejs, E.; McClure, C.K J Am.Chem Soc.1986, 108, 1094; Evans, D.A.; Kaldor, S.W J Org Chem 1990, 55, 1698
1828Lohray, B.B Tetrahedron Asymmetry1992, 3, 1317; Zaitsev, A.B.; Adolfsson, H Synthesis 2006, 1725
1829McNamara, C.A.; King, F.; Bradley, M Tetrahedron Lett.2004, 45, 8527; Jiang, R.; Kuang, Y.; Sun, X.;Zhang, S Tetrahedron Asymmetry2004, 15, 743
1830Wai, J.S.M.; Marko, I.; Svendsen, J.S.; Finn, M.G.; Jacobsen, E.N.; Sharpless, K.B J Am Chem Soc.1989,
111, 1123; Sharpless, K.B.; Amberg, W.; Beller, M.; Chens, H.; Hartung, J.; Kawanami, Y.; L€ubben, D.; Manoury,E.; Ogino, Y.; Shibata, T.; Ukita, T J Org Chem.1991, 56, 4585
Trang 24Sharpless asymmetric dihydroxylation.1831Other chiral ligands1832have also been used,
as well as polymer1833and silica-bound1834Cinchona alkaloids These amines bind to the OsO4in situ as chiral ligands, causing it to add asymmetrically.1835This has been done both with the stoichiometric and with the catalytic method.1836The catalytic method has been extended to conjugated ketones1837and to conjugated dienes, which give tetrahy- droxy products diastereoselectively.1838 Asymmetric dihydroxylation has also been reported with chiral alkenes.1839 Ligands 121 and 122 not only cause enantioselective addition, but also accelerate the reaction, so that they may be useful even where enantioselective addition is not required.1840Although 121 and 122 are not enantiomers, they give enantioselective addition to a given alkene in the opposite sense; for example, styrene predominantly gave the (R) diol with 121, and the (S) diol with 122.1841Note that ionic liquids have been used in asymmetric dihydroxylation.1842
NNOO
NN
NNOO
NN
NN
is prepared from dihydroquinine (DHQ) and PHAL The actual oxidation using AD-mix
a or b- uses 124 or 123, respectively, mixed with potassium osmate [K2OsO2(OH)6], powdered K3Fe(CN)6, and powdered K2CO3in an aqueous solvent mixture.1843One study
1831Kolb, H.C.; Van Nieuwenhze, M.S.; Sharpless, K.B Chem Rev.1994, 94, 2483 Also see, Smith, M.B.Organic Synthesis, 3rd ed., Wavefunction Inc./Elsevier, Irvine, CA/London, England,2010, pp 294–301
1832Wang, L.; Sharpless, K.B J Am Chem Soc.1992, 114, 7568; Xu, D.; Crispino, G.A.; Sharpless, K.B J Am.Chem Soc.1992, 114, 7570; Rosini, C.; Tanturli, R.; Pertici, P.; Salvadori, P Tetrahedron Asymmetry 1996, 7,2971; Sharpless, K.B.; Amberg, W.; Bennani, Y.L.; Crispino, G.A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.;Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L J Org Chem.1992, 57, 2768
See Corey, E.J.; Noe, M.C J Am Chem Soc.1996, 118, 319; Norrby, P.-O.; Kolb, H.C.; Sharpless, K.B J
Am Chem Soc.1994, 116, 8470; Wu, Y.-D.; Wang, Y.; Houk, K.N J Org Chem 1992, 57, 1362 Also seeNelson, D.W.; Gypser, A.; Ho, P.T.; Kolb, H.C.; Kondo, T.; Kwong, H.-L.; McGrath, D.V.; Rubin, A.E.; Norrby,P.-O.; Gable, K.P.; Sharpless, K.B J Am Chem Soc.1997, 119, 1840
1836
See Annunziata, R.; Cinquini, M.; Cozzi, F.; Raimondi, L.; Stefanelli, S Tetrahedron Lett.1987, 28, 3139;Hirama, M.; Oishi, T.; It^o, S J Chem Soc., Chem Commun 1989, 665
1837
Walsh, P.J.; Sharpless, K.B Synlett1993, 605
1838Park, C.Y.; Kim, B.M.; Sharpless, K.B Tetrahedron Lett.1991, 32, 1003
1839Oishi, T.; Iida, K.; Hirama, M Tetrahedron Lett.1993, 34, 3573
1840See Jacobsen, E.N.; Marko, I.; France, M.B.; Svendsen, J.S.; Sharpless, K.B J Am Chem Soc.1989, 111,737
1841Jacobsen, E.N.; Marko, I.; Mungall, W.S.; Schr€oder, G.; Sharpless, K.B J Am Chem Soc 1988, 110, 1968
1842See Branco, L.C.; Afonso, C.A.M J Org Chem.2004, 69, 4381
1843Sharpless, K.B.; Amberg, W.; Bennani, Y.L.; Crispino, G.A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.;Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L J Org Chem.1992, 57, 2768
Trang 25showed that osymylation does not always occur preferentially on the most electron-rich double bond There are examples of the less-rich double bond reacting preferentially, and such preferences may be amplified using AD type reagents, which adds significant steric hindrance to the overall system.1844
These additives have been used in conjunction with microencapsulated OsO4,1845and polymer bound 123 has been used.1846 An asymmetric dihydroxylation was reported catalyzed by ionic polymer-supported OsO4.1847 A catalytic amount of flavin has been used.1848 Both 1231849
and 1241850
have been used to generate diols with high selectivity Oxidation of a terminal alkene with AD-mix and then oxidation with TEM- PO/NaOCl/NaOCl2leads to a-hydroxyl carboxylic acids with high enantioselectivity.1851
enantio-Enantioselective and diastereoselective addition have also been achieved by using preformed derivatives of OsO4, already containing chiral ligands,1852 and by the use of OsO4on alkenes that have a chiral group elsewhere in the molecule.1853A Rh catalyzed diboration of alkenes in the presence of a chiral ligand, leads to the corresponding diol with good enantioselectivity after oxidation.1854
Alkenes can also be oxidized with metallic acetates [e.g., lead tetraacetate1855 or thallium(III) acetate]1856 to give bis(acetates) of glycols.1857 Oxidizing agents (e.g., benzoquinone, MnO2, or O2), along with palladium acetate, have been used to convert conjugated dienes to 1,4-diacetoxy-2-alkenes (1,4-addition).1858
1,2-Diols are also generated from terminal alkynes by two sequential reactions with a
Pt catalyst and then a Pd catalyst, both with HSiCl3, and a final oxidation with
H2O2KF.1859 The dihydroxylation of a vinyl ether, derived from an alkyne, leads to a-hydroxy aldehydes.1860Dihydroxylation of alkenes has been reported using a lipase and hydrogen peroxide, under microwave irradiation.1861 A Pd catalyzed diacetoxylation is also known.1862
1844For a review, see FranScais, A.; Bedel, O.; Haudrechy, A Tetrahedron 2008, 64, 2495
1845Kobayashi, S.; Ishida, T.; Akiyama, R Org Lett.2001, 3, 2649
1846Kuang, Y.-Q.; Zhang, S.-Y.; Wei, L.-L Tetrahedron Lett.2001, 42, 5925
1847Lee, B.S.; Mahajan, S.; Janda, K.D Tetrahedron Lett.2005, 46, 4491
1848Jonsson, S.Y.; Adolfsson, H.; B€ackvall, J.-E Org Lett 2001, 3, 3463
1849Krief, A.; Colaux-Castillo, C Tetrahedron Lett.1999, 40, 4189
S Synthetic Reagents, Vol 5, Wiley, NY,1983, pp 165–187
1857For another method see Fristad, W.E.; Peterson, J.R Tetrahedron1984, 40, 1469
1858See B€ackvall, J.E.; Awasthi, A.K.; Renko, Z.D J Am Chem Soc 1987, 109, 4750 and references citedtherein; B€ackvall, J.E Bull Soc Chim Fr 1987, 665; New J Chem 1990, 14, 447 For another method, seeUemura, S.; Fukuzawa, S.; Patil, S.R.; Okano, M J Chem Soc Perkin Trans 1,1985, 499
1859Shimada, T.; Mukaide, K.; Shinohara, A.; Han, J.W.; Hayashi, T J Am Chem Soc.2004, 124, 1584
1860DeBergh, J.R.; Spivey, K.M.; Ready, J.M J Am Chem Soc.2008, 130, 7828
1861Sarma, K.; Borthakur, N.; Goswami, A Tetrahedron Lett.2007, 48, 6776
1862
Wang, A.; Jiang, H.; Chen, H J Am Chem Soc.2009, 131, 3846
Trang 261,2-Dithiols can be prepared from alkenes by largely indirect methods.1863
OS II, 307; III, 217; IV, 317; V, 647; VI, 196, 342, 348; IX, 251, 383.
15-49 Dihydroxylation of Aromatic Rings
Dihydroxy-addition
OHOH
Pseudomonas putida
One p bond of an aromatic ring can be converted to a cyclohexadiene 1,2-diol by reaction with enzymes associated with P putida.1864 A variety of substituted aromatic compounds can be oxidized, including bromobenzene, chlorobenzene,1865and toluene.1866
In these latter cases, introduction of the hydroxyl groups generates a chiral molecule that can be used as a template for asymmetric syntheses.1867
OS X, 217.
15-50 Epoxidation (Addition of Oxygen, Oxygen)
epi-Oxy-addition
OR
O
OOH
+
RO
OH+
Alkenes are converted to epoxides (oxiranes) by reaction with many peroxyacids.1868The reaction, called the Prilezhaev reaction, has wide utility.1869 The most common is probably m-chloroperoxybenzoic acid, but peroxyacetic and peroxybenzoic are available, and trifluoroperoxyacetic acid1870 and 3,5-dinitroperoxybenzoic acid1871are particularly reactive The limiting factor concerning choice of the peroxyacid is usually whether or not
it is commercially available because an in-lab preparation is potentially rather dangerous Magnesium monoperoxyphthalate (MMPP)1872is commercially available, and has been shown to be a good substitute for m-chloroperoxybenzoic acid in a number of reactions.
1863Elgemeie, G.H.; Sayed, S.H Synthesis2001, 1747
1864
Gibson, D.T.; Koch, J.R.; Kallio, R.E Biochemistry1968, 7, 2653; Brown, S.M in Hudlicky, T OrganicSynthesis: Theory and Practice JAI Press, Greenwich, CT.,1993, Vol 2, p 113; Carless, H.A.J TetrahedronAsymmetry1992, 3, 795
Hudlicky, T.; Gonzalez, D.; Gibson, D.T Aldrichimica Acta1999, 32, 35; Ley, S.V.; Redgrave, A.J Synlett
1990, 393 Also see, Smith, M.B Organic Synthesis, 3rd ed., Wavefunction Inc./Elsevier, Irvine, CA/London,England,2010, pp 303–306
1868
For a list of reagents, including peroxyacids and others, used for epoxidation, with references, see Larock,R.C Comprehensive Organic Transformations, 2nd ed., Wiley–VCH, NY,1999, pp 915–927
1869See Hudlicky, M Oxidations in Organic Chemistry American Chemical Society, Washington, 1990,
pp 60–64; Haines, A.H Methods for the Oxidation of Organic Compunds, Academic Press, NY, 1985,
pp 98–117, 295–303; Dryuk, V.G Russ Chem Rev.1985, 54, 986; Plesnicar, B in Trahanovsky, W.S Oxidation
in Organic Chemistry pt C, Academic Press, NY,1978, pp 211–252; Hiatt, R in Augustine, R.L.; Trecker, D.J.Oxidation, Vol 2; Marcel Dekker, NY,1971; pp 113–140
1870Emmons, W.D.; Pagano, A.S J Am Chem Soc.1955, 77, 89
1871Rastetter, W.H.; Richard, T.J.; Lewis, M.D J Org Chem.1978, 43, 3163
1872
Foti, C.J.; Fields, J.D.; Kropp, P.J Org Lett.1999, 1, 903
Trang 27Alkyl, aryl, hydroxyl, ester, and other groups may be present, but not amino groups since they are oxidized by the reagent The presence of electron-donating groups increases the rate, and the reaction is particularly rapid with tetraalkyl alkenes Conditions are mild and yields are high Transition metal catalysts can facilitate epoxidation of alkenes at low temperatures or with alkenes that may otherwise react sluggishly.1873
OR
OOO
O
OH+
125
The one-step mechanism involving a transition state (e.g., 125)1874 was proposed by Bartlett.1875Evidence for this concerted mechanism is as follows1876: (1) The reaction is second order If ionization were the rate-determining step, it would be first order in peroxyacid (2) The reaction readily takes place in nonpolar solvents, where formation of ions is inhibited.1877(3) Measurements of the effect on the reaction rate of changes in the substrate structure show that there is no carbocation character in the transition state.1878(4) The addition is stereospecific (i.e., a trans-alkene gives a trans-epoxide and a cis-alkene gives a cis-epoxide) even in cases where electron-donating substituents would stabilize a hypothetical carbocation intermediate.1879 However, where there is an OH group in the allylic or homoallylic position, the stereospecificity diminishes or disappears, with both cis and trans isomers giving predominantly and exclusively the product where the incoming oxygen is syn to the OH group This probably indicates a transition state in which there is hydrogen bonding between the OH group and the peroxyacid.1880
In general, peroxides (HOOH1881and ROOH) are poor reagents for epoxidation of simple alkenes since OH and OR are poor leaving groups in the concerted mechanism shown above.1882 Transition metal catalysts1883 have been used with alkyl hydroperoxides,1884
1873Stack, T.D.P Org Lett.2003, 5, 2469; Murphy, A.; Pace, A.; Stack, T.D.P Org Lett 2004, 6, 3119.1874
See Finn, M.G.; Sharpless, K.B in Morrison, J.D Asymmetric Synthesis Vol 5, Wiley, NY,1985, pp 247–308; Bach, R.D.; Canepa, C.; Winter, J.E.; Blanchette, P.E J Org Chem.1997, 62, 5191; Freccero, M.; Gandolfi,R.; Sarzi-Amade, M.; Rastelli, A J Org Chem 2002, 67, 8519
1875
Bartlett, P.D Rec Chem Prog.,1957, 18, 111 For other proposed mechanisms see Kwart, H.; Hoffman, D.M
J Org Chem.1966, 31, 419; Hanzlik, R.P.; Shearer, G.O J Am Chem Soc 1975, 97, 5231
1876Freccero, M.; Gandolfi, R.; Sarzi-Amade, M.; Rastelli, A J Org Chem 2004, 69, 7479 See also, Vedejs, E.;Dent III, W.H.; Kendall, J.T.; Oliver, P.A J Am Chem Soc.1996, 118, 3556
1877See Gisdakis, P.; R€osch, N Eur J Org Chem 2001, 719
1878
Schneider, H.; Becker, N.; Philippi, K Chem Ber.1981, 114, 1562; Batog, A.E.; Savenko, T.V.; Batrak, T.A.;Kucher, R.V J Org Chem USSR1981, 17, 1860
1879See Freccero, M.; Gandolfi, R.; Sarzi-Amade, M.; Rastelli, A J Org Chem.2000, 65, 8948
1880See Houk, K.N.; Liu, J.; DeMello, N.C.; Condroski, K.R J Am Chem Soc.1997, 119, 10147
1881Arends, I.W.C.E Angew Chem Int Ed.2006, 45, 6250
1882See Deubel, D.V.; Frenking, G.; Gisdakis, P.; Herrmann, W.A.; R€osch, N.; Sundermeyer, J Acc Chem Res
2004, 37, 645
1883La: Nemoto, T.; Kakei, H.; Gnanadesikan, V.; Tosaki, S.-y.; Ohshima, T.; Shibasaki, M J Am Chem Soc
2002, 124, 14544 Mn: Lane, B.S.; Vogt, M.; De Rose, V.T.; Burgess, K J Am Chem Soc 2002, 124, 11946 Ti:Lattanzi, A.; Iannece, P.; Screttri, A Tetrahedron Lett.2002, 43, 5629 Pd: Yu, J.-Q.; Corey, E.J Org Lett 2002,
4, 2727.Ru: Adam, W.; Alsters, P.L.; Neumann, R.; Saha-M€oller, C.; Sloboda-Rozner, D.; Zhang, R Synlett 2002,
2011.V: Sharpless, K.B.; Verhoeven, T.R Aldrichimica Acta 1979, 12, 63; Torres, G.; Torres, W.; Prieto, J.A.Tetrahedron2004, 60, 10245
1884
See Hiatt, R in Augustine, R.L.; Trecker, D.J Oxidation, Vol 2, Marcel Dekker, NY,1971, p 124
Trang 28however Epoxidation occurs with Fe,1885and with Ti1886or V catalysts.1887In the presence
of some other reagents,1888 peroxides give good yields of the epoxide These coreagents include DCC,1889magnesium aluminates,1890metalloporphyrins,1891hydrotalcite1892with microwave irradiation,1893and arsines in fluorous solvents.1894The catalyst MeReO31895has been used for epoxidation using sodium percarbonate and pyrazole,1896 or hydrogen peroxide,1897or urea–H2O2.1898
Epoxidation has been done in ionic liquids using 10% H2O2with MnSO41899 or an
Fe catalyst.1900Hypervalent iodine compounds [e.g., PhI(OAc)2], in conjunction with a
Ru catalyst in aqueous media, converts alkenes to epoxides.1901This reagent has been used
in an ionic liquid with a Mn catalyst.1902 Sodium chlorite (NaClO2) in water gives epoxidation from alkenes.1903Microwave assisted epoxidations are known using H2O2.1904Epoxidation of vinyl ethers has been studied.1905
Several homogeneous and heterogeneous asymmetric epoxidation protocols have been developed.1906 Enzymatic epoxidation1907 and epoxidation with catalytic antibodies1908have been reported Organocatalysts (e.g., chiral iminium salts) have been used.1909Asymmetric Weitz–Scheffer epoxidation1910 (epoxidation of electron-deficient alkenes
1885
Anilkumar, G.; Bitterlich, B.; Gelalcha, F.G.; Tse, M.K.; Beller, M Chem Commun.2007, 289; Bitterlich,B.; Schr€oder, K.; Tse, M.K.; Beller, M Eur J Org Chem 2008, 4867
1886
Sawada, Y.; Matsumoto, K.; Katsuki, T Angew Chem Int Ed.2007, 46, 4559; Malkov, A.V.; Bourhani, Z.;
Ko9covsky, P Org Biomol Chem 2005, 3, 3194; Matsumoto, K.; Sawada, Y.; Katsuki, T Pure Appl Chem 2008,
1890Yamaguchi, K.; Ebitani, K.; Kaneda, K J Org Chem.1999, 64, 2966
1891Chan, W.-K.; Liu, P.; Yu, W.-Y.; Wong, M.-K.; Che, C.-M Org Lett.2004, 6, 1597
1892For an example without microwave irradiation, see Pillai, U.R.; Sahle-Demessie, E.; Varma, R.S Synth.Commun.2003, 33, 2017
1893Pillai, U.R.; Sahle-Demessie, E.; Varma, R.S Tetrahedron Lett.2002, 43, 2909
1894Van Vliet, M.C.A.; Arends, I.W.C.E.; Sheldon, R.A Tetrahedron Lett.1999, 40, 5239
1895Yamazaki, S Tetrahedron2008, 64, 9253; Yamazaki, S Org Biomol Chem 2007, 5, 2109–2113; Saladino,R.; Neri, V.; Pelliccia, A.R.; Caminiti, R.; Sadun, C J Org Chem.2002, 67, 1323
1896
Vaino, A.R J Org Chem.2000, 65, 4210
1897See Iskra, J.; Bonnet-Delpon, D.; Begue, J.-P Tetrahedron Lett 2002, 43, 1001
Srinivas, K.A.; Kumar, A.; Chauhan, S.M.S Chem Commun.2002, 2456
1901Tse, M.K.; Bhor, S.; Klawonn, M.; D€obler, C.; Beller, M Tetrahedron Lett 2003, 44, 7479
Orendt, A.M.; Roberts, S.W.; Rainier, J.D J Org Chem.2006, 71, 5565
1906Xia, Q.-H.; Ge, H.-Q.; Ye, C.-P.; Liu, Z.-M.; Su, K.-X Chem Rev.2005, 105, 1603
1907Kubo, T.; Peters, M.W.; Meinhold, P.; Arnold, F.H Chemistry: European J.2006, 12, 1216 For a method ofelectrochemical regenration of monooxygenase, see Hollmann, F.; Hofstetter, K.; Habicher, T.; Hauer, B.; Schmid,
A J Am Chem Soc.2005, 127, 6540
1908Chen, Y.; Reymond, J.-L Synthesis2001, 934
1909Bulman Page, P.C.; Buckley, B.R.; Rassias, G.A.; Blacker, A.J Eur J Org Chem.2006, 803
1910Weitz, E.; Scheffer, A Chem Ber.1921, 54, 2327 See Enders, D.; Zhu, J.; Raabe, G Angew Chem Int Ed
1996, 35, 1725
Trang 29using H2O2 in a strong alkaline solution) is common Cinchona-derived phase-transfer catalysts, initially used by Wynberg, are now common.1911 Enantioselectivities can be significantly improved by changes of the catalyst structure, as well as the type of oxidant.1912 A Yb BINOL complex, with t-BuOOH led to epoxidation of conjugated ketones with high asymmetric induction,1913as did a mixture of NaOCl and a Cinchona alkaloid.1914Treatment with aq NaOCl1915or with an alkyl hydroperoxide1916and a chiral phase-transfer agent leads to chiral nonracemic epoxy-ketones Epoxides can also be prepared by treating alkenes with oxygen or with an alkyl peroxide1917 catalyzed by a complex of a transition metal (e.g., V, Mo, Ti, La,1918Y,1919or Co).1920The use of chiral additive leads to enantioselective epoxidation,1921and organocatalysts have been used as well.1922Chiral hydroperoxides have been used for enantioselective epoxidation.1923Other epoxidation methods are available Dioxiranes,1924 (e.g., dimethyl dioxirane, 126),1925either isolated or generated in situ,1926are important epoxidation reagents With dimethyloxirane, C H insertion reactions can occur preferentially.1927The reaction with alkenes is rapid, mild, safe, and a variety of methods have been developed using an oxidant
as a coreagent Substituent effects in such reactions have been studied1928 and also substrate variations.1929 The most commonly used coreagent is probably potassium peroxomonosulfate (KHSO5) Oxone (2KHSO5 KHSO4 K2SO4) is a common source
of KHSO5 Oxone reacts with ketones1930and sodium bicarbonate to convert an alkene to
1911
Helder, R.; Hummelen, J.C.; Laane, R.W.P.M.; Wiering, J.S.; Wynberg, H Tetrahedron Lett.1976, 17, 1831;Wynberg, H.; Marsman, B J Org Chem.1980, 45, 158; Pluim, H.; Wynberg, H J Org Chem 1980, 45, 2498.1912
Arai, S.; Shirai, Y.; Ishida, T.; Shioiri, T Tetrahedron1999, 55, 6375; Corey, E.J.; Zhang, F.-Y Org Lett
1999, 1, 1287; Lygo, B.; Wainwright, P.G Tetrahedron 1999, 55, 6289 See Adam, W.; Rao, P.B.; Degen, H.-G.;Levai, A.; Patonay, T.; Saha-Moller, C.R J Org Chem.2002, 67, 259
1913
Watanabe, S.; Arai, T.; Sasai, H.; Bougauchi, M.; Shibasaki, M J Org Chem.1998, 63, 8090.1914
Lygo, B.; Wainwright, P.G Tetrahedron Lett.1998, 39, 1599
1915Lygo, B.; To, D.C.M Tetrahedron Lett.2001, 42, 1343
1916Adam, W.; Rao, P.B.; Degen, H.-G.; Saha-M€oller, C.R Tetrahedron Asymmetry 2001, 12, 121
1917For example, see Ledon, H.J.; Durbut, P.; Varescon, F J Am Chem Soc.1981, 103, 3601; Mimoun, H.;Mignard, M.; Brechot, P.; Saussine, L J Am Chem Soc.1986, 108, 3711; Laszlo, P.; Levart, M.; Singh, G.P.Tetrahedron Lett.1991, 32, 3167
1918Nemoto, T.; Ohshima, T.; Shibasaki, M J Am Chem.Soc.2001, 123, 9474
1919Kakei, H.; Tsuji, R.; Ohshima, T.; Shibasaki, M J Am Chem Soc.2005, 127, 8962
Lu, J.; Xu, Y.-H.; Liu, F.; Loh, T.-P Tetrahedron Lett.2008, 49, 6007
1923Kosnik, W.; Bocian, W.; Kozerski, L.; Tvaro9ska, I.; Chmielewski, M Chemistry: European J 2008, 14, 6087.1924
Murray, R.W Chem Rev.1989, 89, 1187; Adam, W.; Curci, R.; Edwards, J.O Acc Chem Res 1989, 22, 205;Curci, R.; Dinoi, A.; Rubino, M.E Pure Appl Chem.1995, 67, 811; Clennan, E.L Trends in Organic Chemistry
1995, 5, 231; Denmark, S.E.; Wu, Z Synlett 1999, 847; Annese, C.; D’Accolti, L.; Dinoi, A.; Fusco, C.; Gandolfi,R.; Curci, R J Am Chem Soc.2008, 130, 1197
1927Adam, W.; Prechtl, F.; Richter, M.J.; Smerz, A.K Tetrahedron Lett.1993, 34, 8427
1928D€ufert,, A.; Werz, D.B J Org Chem 2008, 73, 5514
1929Nieto, N.; Munslow, I.J.; Fernandez-Perez, H.; Vidal-Ferran, A Synlett 2008, 2856
1930Sartori, G.; Armstrong, A.; Maggi, R.; Mazzacani, A.; Sartorio, R.; Bigi, F.; Dominguez-Fernandez, B
J Org Chem.2003, 68, 3232
Trang 30an epoxide Oxone converts alkenes to epoxides in the presence of certain additives (e.g., N,N-dialkylalloxans).1931Oxone, with hydrogen peroxide or a similar oxidant, can be used with chiral ketones1932or aldehydes to convert alkenes to chiral, nonracemic epoxides.1933This reaction probably converts alkenes to epoxides with good enantioselectivity by in situ generation of dioxirane.1934 Chiral dioxiranes have reportedly given nonracemic epoxides.1935 This transformation with chiral carbohydrates is sometimes called Shi epoxidation.1936Epoxidation does not occur in good yields with these reagents in most other solvents, and it is suggested that the active agent that generates dioxirane is peroxyimidic acid [MeC( NH)OOH].1937
Note that benzaldehyde with
Chloramine-M1938will convert alkenes to epoxides.1939
OOxirene
OO
RR
126
ONR
1933See Tian, H.; She, X.; Yu, H.; Shu, L.; Shi, Y J Org Chem.2002, 67, 2435; Denmark, S.E.; Matsuhashi, H J.Org Chem.2002, 67, 3479; Arsmtrong, A.; Ahmed, G.; Dominguez-Fernandez, B.; Hayter, B.R.; Wailes, J.S J.Org Chem.2002, 67, 8610; Wu, X.-Y.; She, X.; Shi, Y J Am Chem Soc 2002, 124, 8792; Bez, G.; Zhao, C.-G.Tetrahedron Lett.2003, 44, 7403; Chan, W.-K.; Yu, W.-y.; Che, C.-M.; Wong, M.-K J Org Chem 2003, 68,6576
Yang, D.; Zhang, C.; wang, X.-C J Am Chem Soc.2000, 122, 4039
1940See Bohe, L.; Kammoun, M Tetrahedron Lett 2002, 43, 803; Bohe, L.; Kammoun, M Tetrahedron Lett
2004, 45, 747
1941See Washington, I.; Houk, K N J Am Chem Soc.2000, 122, 2948
1942See Jacobson, E N in Ojima, I Catalytic Asymmetric Synthesis VCH, NY,1993, pp 159–203; Page, P.C.B.;Barros, D.; Buckley, B.R.; Ardakani, A.; Marples, B.A J Org Chem 2004, 69, 3595; Page, P.C.B.;Buckley, B.R.; Blacker, A.J Org Lett.2004, 6, 1543
1943Wong, O.A.; Shi, Y Chem Rev.2008, 108, 3958; Page, P.C.B.; Buckley, B.R.; Farah, M.M.; Blacker, A.J.Eur J Org Chem.2009, 3413
1944
Biscoe, M.R.; Breslow, R J Am Chem Soc.2005, 127, 10812
Trang 31Although cis–trans isomerization of epoxides is not formally associated with this section, it is a potential issue in the conversion of an alkene to an epoxide There are several catalysts for this process.1945
It would be useful if triple bonds could be similarly epoxidized to give oxirenes (see oxirene, above), but they are not stable compounds.1946Two oxirenes have been trapped in solid argon matrices at very low temperatures, but they decayed upon warming to 35 K.1947Oxirenes probably form in the reaction,1948but react further before they can be isolated Note that oxirenes bear the same relationship to cyclobutadiene that furan does to benzene and may therefore be expected to be antiaromatic (Sec 2.B and 2.K.ii).
Conjugated dienes can be epoxidized (1,2-addition), although the reaction is slower than for corresponding alkenes, but a,b-unsaturated ketones do not generally give epoxides when treated with peroxyacids.1949The epoxidation of a,b-unsaturated ketones with H2O2under basic conditions is known as the Waits–Scheffer epoxidation, discovered
in 1921.1950 This fundamental reaction has been extended to a,b-unsaturated ketones (including quinones), aldehydes, and sulfones.1951 This is a nucleophilic addition by a Michael-type mechanism, involving attack by HO2 1952: This reaction is another example
of 1,4-addition of a heteroatom-containing species, as discussed in Reaction 15-31.
O
HOO
OO
a,b-Unsaturated compounds can be epoxidized alkyl hydroperoxides and a base,1953
or with H2O2and a base1954or heteropoly acids.1955The reaction has been done with LiOH and polymer-bound quaternary ammonium salts.1956
Another important asymmetric epoxidation of a conjugated system is the reaction of alkenes with polyleucine,1957DBU, and urea–H2O2, giving an epoxy–carbonyl compound with good enantioselectivity.1958 The hydroperoxide anion epoxidation of conjugated
1945Lo, C.-Y.; Pal, S.; Odedra, A.; Liu, R.-S Tetrahedron Lett.2003, 44, 3143
1946See Lewars, E.G Chem Rev.1983, 83, 519
1947Torres, M.; Bourdelande, J.L.; Clement, A.; Strausz, O.P J Am Chem Soc.1983, 105, 1698 See also,Laganis, E.D.; Janik, D.S.; Curphey, T.J.; Lemal, D.M J Am Chem Soc.1983, 105, 7457
1954See Marigo, M.; Franzen, J.; Poulsen, T.B.; Zhuang, W.; Jørgensen, K.A J Am Chem Soc 2005, 127, 6964
1955Oguchi, T.; Sakata, Y.; Takeuchi, N.; Kaneda, K.; Ishii, Y.; Ogawa, M Chem Lett.1989, 2053
1956Anand, R.V.; Singh, V.K Synlett2000, 807
1957For a mechanistic discussion of polypeptide catalyzed epoxidation, see Mathew, S.P.; Gunathilagan, S.;Roberts, S.M.; Blackmond, D.G Org Lett.2005, 7, 4847
1958Allen, J.V.; Drauz, K.-H.; Flood, R.W.; Roberts, S.M.; Skidmore, J Tetrahedron Lett.1999, 40, 5417; Geller,T.; Roberts, S.M J Chem Soc., Perkin Trans 1,1999, 1397; Bentley, P.A.; Bickley, J.F.; Roberts, S.M.; Steiner,
A Tetrahedron Lett.2001, 42, 3741
Trang 32carbonyl compounds with a polyamino acid (e.g., poly-L-alanine or poly-L-leucine is known as the Juli a–Colonna epoxidation.1959Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq NaOCl and a Cinchona alkaloid derivative as catalyst.1960 A triphasic phase-transfer catalysis protocol has also been developed.1961b-Peptides have been used as catalysts in this reaction.1962
When a carbonyl group is elsewhere in the molecule, but not conjugated with the double bond, the Baeyer–Villiger Reaction ( 18-19) may compete Allenes1963 are converted by peroxyacids to allene oxides1964or spiro dioxides, both of which species can in certain cases be isolated,1965but more often are unstable under the reaction conditions and react further to give other products.1966
Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves,1967 or with peroxyacids.1968 The addition of an appropriate chiral ligand to the metal-catalyzed hydroperoxide epoxidation of allylic alcohols leads to high enantioselectivity This important modification is known as the Sharpless asymmetric epoxidation,1969where allylic alcohols are converted to optically active epoxides with excellent enantioselectivity by treatment with t-BuOOH, titanium tetraisopropoxide, and optically active diethyl tartrate.1970The Ti(OCHMe2)4and diethyl tartrate can be present in catalytic amounts (15–10 mol%) if molecular sieves are present.1971Polymer- supported catalysts have also been reported.1972 The use of a tartrate–PEG reagent (PEG350or PEG750) allows generation of both enantiomers.1973Both ( þ) and () diethyl tartrate are readily available, so either enantiomer of the product can be prepared The method has been successful for a wide range of primary allylic alcohols, including substrates where the double bond is mono-, di, tri-, and tetrasubstituted,1974and is highly useful in natural product synthesis The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound1975formed from the titanium
1959Banfi, S.; Colonna, S.; Molinari, H.; Julia, S.; Guixer, J Tetrahedron, 1984, 40, 5207 For reviews, see Lin, P.Tetrahedron: Asymmetry1998, 9, 1457; Ebrahim, S.; Wills, M Tetrahedron; Asymmetry 1997, 8, 3163
1960Lygo, B.; Wainwright, P.G Tetrahedron1999, 55, 6289
1961Geller, T.; Kr€uger, C.M.; Militzer, H.-C Tetrahedron Lett 2004, 45, 5069
1962Coffey, P.E.; Drauz, K.-H.; Roberts, S.M.; Skidmore, J.; Smith, J.A Chem Commun.2001, 2330
1963See Jacobs, T.L in Landor, S.R The Chemistry of Allenes Vol 2, Academic Press, NY,1982, pp 417–510,483–491
pp 284–290
1970
Sharpless, K.B.; Woodard, S.S.; Finn, M.G Pure Appl Chem.1983, 55, 1823 and references cited therein
1971Gao, Y.; Hanson, R.M.; Klunder, J.M.; Ko, S.Y.; Masamune, H.; Sharpless, K.B J Am Chem Soc.1987, 109,
5765 See Massa, A.; D’Ambrosi, A.; Proto, A.; Screttri, A Tetrahedron Lett.2001, 42, 1995 For anotherimprovement, see Wang, Z.; Zhou, W Tetrahedron1987, 43, 2935
1972Canali, L.; Karjalainen, J.K.; Sherrington, D.C.; Hormi, O Chem Commun.1997, 123
1973Reed, N.N.; Dickerson, T.J.; Boldt, G.E.; Janda, K.D J Org Chem.2005, 70, 1728
1974See the table in Finn, M.G.; Sharpless, K.B in Morrison, J.D Asymmetric Synthesis Vol 5, Academic Press,
NY,1985, pp 249–250 See also, Schweiter, M.J.; Sharpless, K.B Tetrahedron Lett 1985, 26, 2543.1975
See Williams, I.D.; Pedersen, S.F.; Sharpless, K.B.; Lippard, S.J J Am Chem Soc.1984, 106, 6430
Trang 33alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the t-BuOOH.1976
Ordinary alkenes (without an allylic OH group) do not give optically active alcohols by the Sharpless protocol because binding to the catalyst is necessary for enantioselectivity Homoallylic alcohols have been converted to the epoxide, however, using a V catalyst in the presence of a chiral bis(hydroxyamide).1977 Simple alkenes can be epoxidized enantioselectively with sodium hypochlorite (NaOCl, commercial bleach) and an optically active manganese complex catalyst.1978 Apart from the commonly used NaOCl, urea–
H2O2has been used.1979
The use of a manganese–salen complex1980 with various oxidizing agents, in what is called the Jacobsen–Katsuki reaction.1981Simple alkenes can be epoxidized with high enantioselectivity.1982In addition to Mn, Cr–salen,1983 Ti–salen,1984and Ru–salen com- plexes1985have been used for epoxidation.1986Note that salen ligands are based on salen The mechanism of this reaction has been examined.1987Radical intermediates have been suggested for this reaction,1988A polymer-bound Mn(III)–salen complex, in conjunction with NaOCl, has been used for asymmetric epoxidation,1989 and manganese porphyrin complexes have also been used.1990 Cobalt complexes give similar results.1991 A related epoxidation reaction used an iron complex with molecular oxygen and isopropanal.1992Nonracemic epoxides can be prepared from racemic epoxides with (salen) cobalt(II) catalysts following a modified procedure for kinetic resolution.1993
1976
See Finn, M.G.; Sharpless, K.B in Morrison, J.D Asymmetric Synthesis Vol 5, Academic Press, NY,1985,
p 247 Also see Corey, E.J J Org Chem.1990, 55, 1693; Woodard, S.S.; Finn, M.G.; Sharpless, K.B J Am.Chem Soc.1991, 113, 106; Finn, M.G.; Sharpless, K.B J Am Chem Soc 1991, 113, 113; Takano, S.; Iwebuchi,Y.; Ogasawara, K J Am Chem Soc.1991, 113, 2786; Cui, M.; Adam, W.; Shen, J.H.; Luo, X.M.; Tan, X.J.; Chen,K.X.; Ji, R.Y.; Jiang, H.L J Org Chem.2002, 67, 1427
1977
Zhang, W.; Yamamoto, H J Am Chem Soc.2007, 129, 286
1978Jacobsen, E.N.; Zhang, W.; Muci, A.R.; Ecker, J.R.; Deng, L J Am Chem Soc.1991, 113, 7063 See also,Irie, R.; Noda, K.; Ito, Y.; Katsuki, T Tetrahedron Lett.1991, 32, 1055; Halterman, R.L.; Jan, S J Org Chem
1991, 56, 5253
1979Kureshy, R.I.; Khan, N.H.; Abdi, S.H.R.; Patel, S.T.; Jasra, R.V Tetrahedron Asymmetry2001, 12, 433
1980Wu, M.; Wang, B.; Wang, S.; Xia, C.; Sun, W Org Lett.2009, 11, 3622 See Adam, W.; Mock-Knoblauch,C.; Saha-Moller, C.R.; Herderich, M J Am Chem Soc.2000, 122, 9685
1981Brandes, B.D.; Jacobsen, E.N Tetrahedron Lett.1995, 36, 5123; Nishikori, H.; Ohta, C.; Katsuki, T Synlett
2000, 1557; Tangestaninejad, S.; Habibi, M.H.; Mirkhani, V.; Moghadam, M Synth Commun 2002, 32, 3331.See Fristrup, P.; Dideriksen, B.B.; Tanner, D.; Norrby, P.-O J Am Chem Soc.2005, 127, 13672 For a discussion
on the origin of enantioselectivity, see K€urti, L.; Blewett, M.M.; Corey, E.J Org Lett 2009, 11, 4592.1982
See Nishida, T.; Miyafuji, A.; Ito, Y.N.; Katsuki, T Tetrahedron Lett.2000, 41, 7053
1983
Daly, A.M.; Renehan, M.F.; Gilheany, D.G Org Lett.2001, 3, 663; O’Mahony, C.P.; McGarrigle, E.M.;Renehan, M.F.; Ryan, K.M.; Kerrigan, N.J.; Bousquet, C.; Gilheany, D.G Org Lett.2001, 3, 3435 See thereferences cited therein
1988Cavallo, L.; Jacobsen, H Angew Chem Int Ed.2000, 39, 589
1989Song, C.E.; Roh, E.J.; Yu, B.M.; Chi, D.Y.; Kim, S.C.; Lee, K.J Chem Commun.2000, 615; Ahn, K.-H.;Park, S.W.; Choi, S.; Kim, H.-J.; Moon, C.J Tetrahedron Lett.2001, 42, 2485
1990Konishi, K.; Oda, K.; Nishida, K.; Aida, T.; Inoue, S J Am Chem Soc.1992, 114, 1313
1991Takai, T.; Hata, E.; Yorozu, K.; Mukaiyama, T Chem Lett.1992, 2077
1992Saalfrank, R.W.; Reihs, S.; Hug, M Tetrahedron Lett,1993, 34, 6033
1993
Savle, P.S.; Lamoreaux, M.J.; Berry, J.F.; Gandour, R.D Tetrahedron Asymmetry1998, 9, 1843
Trang 34In a different type of reaction, alkenes are photooxygenated (with singlet O2, see Reaction 14-7) in the presence of a Ti, V, or Mo complex to give epoxy alcohols (e.g., 128), formally derived from allylic hydroxylation followed by epoxidation.1994In other cases, modification of the procedure gives simple epoxidation.1995Alkenes react with aldehydes and oxygen, with Pd-on-silica1996or a Ru catalyst,1997to give the epoxide.
CH2OH OVO(acac)2
an alkene reacts with styrene thiirane to give the new thiirane.2002
OS I, 494; IV, 552, 860; V, 191, 414, 467, 1007; VI, 39, 320, 679, 862; VII, 121, 126, 461; VIII, 546; IX, 288; X, 29; 80, 9.
15-51 Hydroxysulfenylation (Addition of Oxygen, Sulfur)
Hydroxy-arylthio-addition (overall transformation)
Nakayama, J.; Takahashi, K.; Watanabe, T.; Sugihara, Y.; Ishii, A Tetrahedron Lett.2000, 41, 8349
2001Iranpoor, N.; Tamami, B.; Shekarriz, M Synth Commun.1999, 29, 3313
2002Adam, W.; Bargon, R.M.; Schenk, W.A J Am Chem Soc.2003, 125, 3871
2003Trost, B.M.; Ochiai, M.; McDougal, P.G J Am Chem Soc.1978, 100, 7103; See Zefirov, N.S.; Zyk, N.V.;Kutateladze, A.G.; Kolbasenko, S.I.; Lapin, Yu.A J Org Chem USSR1986, 22, 190
2004Bewick, A.; Mellor, J.M.; Owton, W.M J Chem Soc Perkin Trans 1,1985, 1039; Bewick, A.; Mellor, J.M.;Milano, D.; Owton, W.M J Chem Soc Perkin Trans 1,1985, 1045; Samii, Z.K.M.A.E.; Ashmawy, M.I.A.;Mellor, J.M Tetrahedron Lett.1986, 27, 5289
2005
Chung, M.; D’Souza, V.T.; Szmant, H.H J Org Chem.1987, 52, 1741, and other papers in this series
Trang 35with a disulfide (RSSR) and BF3–etherate.2006 This reaction has been carried out intramolecularly.2007In a similar manner, the reaction of alkenes with ceric ammonium nitrate and diphenyl diselenide in methanol leads to vicinally substituted phenylselenyl methyl ethers.2008 Dimethyl diselenide adds to alkenes to form vicinal bis(methylse- lenyl) compounds, in the presence of tin tetrachloride.2009
Halo-ethers can be formed by the reaction of alkenyl alcohols with various reagents Hept-6-en-1-ol reacts with (collidine)2IþPF6, for example, to form 2-iodomethyl-1- oxacycloheptane.2010
15-52 Oxyamination (Addition of Oxygen, Nitrogen)
N-Tosylated b-hydroxy alkylamines, which can be easily hydrolyzed to amines2011, can be prepared2012by treatment of alkenes with the trihydrate of Chloramine-
b-hydroxy-T (N-chloro-p-toluenesulfonamide sodium salt)1690and a catalytic amount of OsO4.2013In some cases, yields can be improved by the use of phase-transfer catalysis.2014The reaction has been carried out enantioselectively.2015Alkenes can be converted to amido alcohols enantioselectivity by modification of this basic scheme The Sharpless asymmetric aminohydroxylation employs a catalyst consisting of Cinchona alkaloid derived ligands and an osmium species in combination with a stoichiometric nitrogen source that also functions as the oxidant.2016 The Cu catalyzed reaction of an alkene with a N-sulfone oxaziridine leads to an oxazolidine.2017 N-Chlorosulfonyl isocyanate has been used to prepare 1,2-amino alcohols.2018 The Cu catalyzed hydroxyamination of alkenes was reported using Boc-hydroxylamine.2019
The reaction of a carbamate with (DHQ)2PHAL ( 124) and the osmium compound, with NaOH and tert-butyl hypochlorite, leads to a diastereomeric mixture of amido alcohols
129 and 130, each formed with high enantioselectivity.2020 An enantioselective hydroxylation of acrylamides has been reported.2021
Brunel, Y.; Rousseau, G Synlett1995, 323
2011See B€ackvall, J.E.; Oshima, K.; Palermo, R.E.; Sharpless, K.B J Org Chem 1979, 44, 1953
2012
Sharpless, K.B.; Chong, A.O.; Oshima, K J Org Chem.1976, 41, 177 See Rudolph, J.; Sennhenn, P.C.;Vlaar, C.P.; Sharpless, K.B Angew Chem Int Ed.1996, 35, 2810
2013
See Fokin, V.V.; Sharpless, K.B Angew Chem Int Ed.2001, 40, 3455
2014Herranz, E.; Sharpless, K.B J Org Chem.1978, 43, 2544
2015Hassine, B.B.; Gorsane, M.; Pecher, J.; Martin, R.H Bull Soc Chim Belg.1985, 94, 759
2016For a review, see Bodkin, J.A.; McLeod, M.D J Chem Soc., Perkin Trans 12002, 2733
2017Michaelis, D.J.; Shaffer, C.J.; Yoon, T.P J Am Chem Soc.2007, 129, 1866
2018Kim, J.D.; Kim, I.S.; Hua, J.C.; Zee, O.P.; Jung, Y.H Tetrahedron Lett.2005, 46, 1079
2019Kalita, B.; Nicholas, K.M Tetrahedron Lett.2005, 46, 1451
2020Li, G.; Chang, H.-T.; Sharpless, K.B Angew Chem., Int Ed.1996, 35, 451
2021
Streuff, J.; Osterath, B.; Nieger, M.; Mu~niz, K Tetrahedron Asymmetry 2005, 16, 3492
Trang 36(DHQ)2PHAL , K2OsO2(OH)4
NaOH , t-BuOCl , ROH , H2O
130
In general, the nitrogen adds to the less sterically hindered carbon of the alkene to give the major product N-Bromoamides, in the presence of a catalytic amount of (DHQ)2PHAL and LiOH converts conjugated esters to b-amido-a-hydroxy esters with good enantioselec- tivity.2022Another oxyamination reaction involves treatment of a Pd complex of the alkene with a secondary or primary amine, followed by lead tetraacetate or another oxidant.2023The organolanthanide-catalyzed alkene hydroamination has been reported.2024With this approach, amino alkenes (not enamines) can be cyclized to form cyclic amines,2025and amino alkynes lead to cyclic imine.2026 The use of synthesized C-12027 and C-2 symmetric2028 chiral organolanthanide complexes give the amino alcohol with good enantioselectivity.
b-Amino alcohols can be prepared by treatment of an alkene with a reagent prepared from HgO and HBF4 along with aniline to give an aminomercurial compound (PhHN CCHgBF4, aminomercuration; see Reaction 15-7), which is hydrolyzed
to PhHN CCOH.2029 The use of an alcohol instead of water gives the sponding amino ether b-Azido alcohols are prepared by the reaction of an alkene with
corre-Me3SiOOSiMe3, Me3SiN3, and 20% (Cl2SnO)n, followed by treatment with aqueous acetic acid.2030
OS VII, 223, 375.
15-53 Diamination (Addition of Nitrogen, Nitrogen)
Di(alkylarylamino)-addition
Ti(OAc)3PhNHR
RPhN NPhR+
Primary (R ¼ H) and secondary aromatic amines react with alkenes in the presence of thallium(III) acetate to give vic-diamines in good yields.2031The reaction is not successful for primary aliphatic amines In another procedure, alkenes can be diaminated by treatment
2022
Demko, Z.P.; Bartsch, M.; Sharpless, K.B Org Lett.2000, 2, 2221
2023B€ackvall, J.E.; Bj€orkman, E.E Acta Chem Scand Ser B 1984, 38, 91; B€ackvall, J.E.; Bystrom, S.E J Org.Chem.1982, 47, 1126
Li, Y.; Marks, T.J J Am Chem Soc.1998, 120, 1757
2027Douglass, M.R.; Ogasawara, M.; Hong, S.; Metz, M.V.; Marks, T.J Organometallics 2002, 21, 283;Giardello, M.A.; Conticello, V.P.; Brard, L.; Gagne, M.R.; Marks, T.J J Am Chem Soc 1994, 116, 10241;Giardello, M.A.; Conticello, V.P.; Brard, L.; Sabat, M.; Rheingold, A.L.; Stern, C.L.; Marks, T.J J Am Chem.Soc.1994, 116, 10212
2028Hong, S.; Tian, S.; Metz, M.V.; Marks, T.J J Am Chem Soc.2003, 125, 14768
2029Barluenga, J.; Alonso-Cires, L.; Asensio, G Synthesis1981, 376
2030Sakurada, I.; Yamasaki, S.; Kanai, M.; Shibasaki, M Tetrahedron Lett.2000, 41, 2415
2031
Gomez Aranda, V.; Barluenga, J.; Aznar, F Synthesis 1974, 504
Trang 37with the Os compounds R3NOsO (R ¼ t-Bu) and R2NOsO2,2032 analogous to the Os compound mentioned at Reaction 15-52.2033The Pd promoted method of Reaction 15-52 has also been extended to diamination.2034Alkenes can also be diaminated2035indirectly
by treatment of the aminomercurial compound mentioned in Reaction 15-52 with a primary or secondary aromatic amine.2036The reaction of an alkene with N-arylsulfonyl dichloroamines (ArSO2NCl2) followed by reaction with aq Na2SO3, gives the anti-vic- diacetamde.2037 The Pd catalyzed addition of saccharin and H(NTs)2with an alkene, in the presence of a hypervalent iodine oxidant leads to a precursor that can be converted to a 1,2-diamine.2038
Two azido groups can be added to double bonds by treatment with sodium azide and iodosobenzene in acetic acid, C C þ NaN3þ PhIO ! N3CCN3.2039
Dienes react with ureas in the presence of a Pd catalyst, to give an oxazolidinone.2040A
Pd catalyzed reaction of dienes with di-tert-butyldiaziridinone also leads to an oxazolidinone.2041
Alkynes react with the bis(tosylate) of ethylenediamine, in the presence of a CuI catalyst, to give a dihydropiperazine.2042
15-54 Formation of Aziridines (Addition of Nitrogen, Nitrogen)
Aziridines can be prepared directly from double-bond compounds by photolysis or thermolysis of a mixture of the substrate and an azide.2043The reaction has been carried out with R ¼ aryl, cyano, EtOOC, and RSO2, as well as other groups The reaction can take place by at least two pathways.
In one pathway, a 1,3-dipolar addition (Reaction 15-58) takes place to give a triazoline, which can be isolated, followed thermal by extrusion of nitrogen (Reaction 17-34) Evidence for the nitrene pathway is most compelling for R ¼ acyl groups In the other, the azide is converted to a nitrene, which adds to the double bond in a manner analogous to
2040Bar, G.L.J.; Lloyd-Jones, G.C.; Booker-Milburn, K.I J Am Chem Soc.2005, 127, 7308
2041Du, H.; Zhao, B.; Shi, Y J Am Chem Soc.2007, 129, 762; Du, H.; Yuan, W.; Zhao, B.; Shi, Y J Am Chem.Soc.2007, 129, 7496; Du, H.; Yuan, W.; Zhao, B.; Shi, Y J Am Chem Soc 2007, 129, 11688
2042Fukudome, Y.; Naito, H.; Hata, T.; Urabe, H J Am Chem Soc.2008, 130, 1820
2043See Dermer, O.C.; Ham, G.E Ethylenimine and Other Aziridines Academic Press, NY,1969, pp 68–79;Muller, L.L.; Hamer, J 1,2-Cycloaddition Reactions, Wiley, NY,1967 See Singh, G.S.; D’hooghe, M.; De Kimpe,
N Chem Rev.2007, 107, 2080
Trang 38that of carbene addition (Reaction 15-64) Sulfonyloxy amines (e.g., ArSO2ONHCO2Et) form an aziridine when treated with CaO in the presence of a conjugated carbonyl compound.2044In the presence of Cu,2045Co,2046or Rh complexes,2047ethyl diazoacetate adds to imines to give aziridines Diazirenes (Sec 5.D.ii) with n-butyllithium converted conjugated amides to the a,b-aziridino amide.2048Calcium oxide has also been used to generate the nitrene,2049 including nitrene precursors that have an attached chiral ester.2050Other specialized reagents have also been used.2051As discussed in Section 5.E, singlet nitrenes add stereospecifically while triplet nitrenes do not Aminonitrenes (R2NN:) have been shown to add to alkenes2052 to give N-substituted aziridines and to triple bonds to give 1-azirines, which arise from rearrangement of the initially formed 2-azirines.2053 N-Aminophthalimide generates a nitrene in the presence of a Pd catalyst, giving an N-phthalimido aziridine upon reaction with electron-deficient alkenes.2054Alkyl azides add to conjugated alkenes in the presence of an acid.2055 Intramolecular aziridination reactions are known (e.g., the Pd catalyzed addition of N-tosyloxycarbamates
to alkenes to form the bicyclic oxaziridinone).2056 Tosylamines react with alkenes in the presence of a Rh catalyst2057 or with iodine/PhI(OAc)2.2058 Trichloroethylsulfamate esters react with PhI(OAc)2 and a Rh catalyst to give the corresponding N-sulfonyl aziridine.2059
Like oxirenes (see Reaction 15-50), 2-azirines are unstable 1-Azirines can be reduced
to give chiral aziridines.2060
R2 R1 R2N-N:
R1
NR2N
Lebel, H.; Huard, K.; Lectard, S J Am Chem Soc.2005, 127, 14198
2057Catino, A.J.; Nichols, J.M.; Forslund, R.E.; Doyle, M.P Org Lett.2005, 7, 2787
2058Fan, R.; Pu, D.; Gan, J.; Wang, B Tetrahedron Lett.2008, 49, 4925
2059Espino, C.G.; Wehn, P.M.; Chow, J.; Du Bois, J J Am Chem Soc.2001, 123, 6935; Wehn, P.M.; Lee, J.;
Du Bois, J Org Lett.2003, 5, 4823; Espino, C.G.; Fiori, K.W.; Kim, M.; Du Bois, J J Am Chem Soc 2004,
126, 15378; Guthikonda, K.; Du Bois, J J Am Chem Soc.2002, 124, 13672; Keaney, G.F.; Wood, J.L.Tetrahedron Lett.2005, 46, 4031; Guthikonda, K.; Wehn, P.M.; Caliando, B.J.; Du Bois, J Tetrahedron 2006,
62, 11331
2060
Roth, P.; Andersson, P.G.; Somfai, P Chem Commun.2002, 1752
Trang 39An alternative preparation of aziridines reacts an alkene with iodine and Chloramine-T, generating the corresponding N-tosyl aziridine.2061Chloramine T and NBS also give the N-tosyl aziridine,2062and Bromamine-T (TsNBrNaþ) or TsNIK and have also been used
in a similar manner,2063,2064Diazoalkanes react with imines to give aziridines.2065Another useful reagent is NsN IPh, which reacts with alkenes in the presence of Rh com- pounds2066 or Cu complexes2067 to give N-Ns aziridines Other sulfonamide reagents can be used,2068including PhI NTs.2069Enantioselective aziridination is possible using this reaction with chiral ligands.2070This reagent has been used in ionic liquids with a
Cu catalyst.2071 Palladium catalyzes such reactions2072 and we can also use methyl trioxorhenium (MeReO3).2073Manganese(salen) catalysts have also been used with this reagent.2074A nitrido Mn(salen) complex was used with ditosyl anhydride, converting a conjugated diene to an allylic N-tosylaziridine.2075 Arylsulfonamides react with alkenes via the nitrene using an Au2076 or a Cu catalyst.2077
Organocatalysts have been used for the enantioselective aziridination of the C C unit
2062
Thakur, V.V.; Sudalai, A Tetrahedron Lett.2003, 44, 989
2063Vyas, R.; Chanda, B.M.; Bedekar, A.V Tetrahedron Lett.1998, 39, 4715; Hayer, M.F.; Hossain, M.M J Org.Chem.1998, 63, 6839 See Antunes, A.M.M.; Bonifacio, V.D.B.; Nascimento, S.C.C.; Lobo, A.M.; Branco, P.S.;Prabhakar, S Tetrahedron2007, 63, 7009
2064Jain, S.L.; Sain, B Tetrahedron Lett.2003, 44, 575
2065Casarrubios, L.; Perez, J.A.; Brookhart, M.; Templeton, J.L J Org Chem 1996, 61, 8358
2066M€uller, P.; Baud, C.; Jacquier, Y Tetrahedron 1996, 52, 1543 Also see, S€odergren, M.J.; Alonso, D.A.;Bedekar, A.V.; Andersson, P.G Tetrahedron Lett.1997, 38, 6897
Robert-2069
Vedernikov, A.N.; Caulton, K.G Org Lett.2003, 5, 2591; Cui, Y.; He, C J Am Chem Soc 2003, 125,
16202 See Nishimura, M.; Minakata, S.; Takahashi, T.; Oderaotoshi, Y.; Komatsu, M J Org Chem.2002, 67,2101
2070
See Gillespie, K.M.; Sanders, C.J.; O’Shaughnessy, P.; Westmoreland, I.; Thickitt, C.P.; Cott, P J Org Chem
2002, 67, 3450
2071
Kantam, M.L.; Neeraja, V.; Kavita, B.; Haritha, Y Synlett2004, 525
2072Antunes, A.M.M.; Marto, S.J.L.; Branco, P.S.; Prabhakar, S.; Lobo, A.M Chem Commun.2001, 405
2073Jean, H.-J.; Nguyen, S.B.T Chem Commun.2001, 235
2074Nishikori, H.; Katsuki, T Tetrahedron Lett.1996, 37, 9245
2075Nishimura, M.; Minakata, S.; Thonchant, S.; Ryu, I.; Komatsu, M Tetrahedron Lett.2000, 41, 7089
2076Li, Z.; Ding, X.; He, C J Org Chem.2006, 71, 5876
2077Jain, S.L.; Sharma, V.B.; Sain, B Synth Commun.2005, 35, 9
2078Vesely, J.; Ibrahem, I.; Zhao, G.-L.; Rios, R.; Cordova, A Angew Chem Int Ed 2007, 46, 778.2079
See Lwowski, W.; Johnson, R.L Tetrahedron Lett.1967, 891
Trang 4015-55 Aminosulfenylation (Addition of Nitrogen, Sulfur)
Arylamino-arylthio-addition
BF3–OEt2PhSNHAr
PhS NHAr+
An amino and an arylthio group can be added to a double bond by treatment with a sulfenanilide (PhSNHAr) in the presence of BF3–etherate.2080The addition is anti, and the mechanism probably involves a thiiranium ion.2081 In another aminosulfenylation procedure, the substrate is treated with dimethyl(methylthio)sulfonium fluoroborate (MeSSMe2 BF4) and ammonia or an amine,2082 the latter acting as a nucleophile This reaction was extended to other nucleophiles:2083 N3,2084NO2, CN,OH, and
OAc to give MeS CCA, where A ¼ N3, NO2, CN, OH, and OAc, respectively.
An RS (R ¼ alkyl or aryl) and an NHCOMe group have been added in an electrochemical procedure.2085
15-56 Acylacyloxylation and Acylamidation (Addition of Oxygen,
Carbon, or Nitrogen, Carbon)
Acyl-acyloxy-addition
RCO+BF4
Ac2O
O R
O O
CH3
An acyl and an acyloxy group can be added to a double bond by treatment with an acyl fluoroborate and acetic anhydride.2086As expected, the addition follows Markovnikov’s rule, with the electrophile Acþgoing to the carbon with more hydrogen atoms In an analogous reaction, an acyl and an amido group can be added to give 131, if a nitrile is used in place of the anhydride Similarly, halo-acetoxylation is known.2087This reaction has also been carried out on triple bonds, to give the unsaturated analogues of 131 (syn addition).2088
2084Sreekumar, R.; Padmakumar, R.; Rugmini, P Chem Commun.1997, 1133
2085Bewick, A.; Coe, D.E.; Mellor, J.M.; Owton, M.W J Chem Soc Perkin Trans 1,1985, 1033
2086Shastin, A.V.; Balenkova, E.S J Org Chem USSR1984, 20, 870
2087Hashem, Md.A.; Jung, A.; Ries, M.; Kirschning, A Synlett1998, 195
2088
Gridnev, I.D.; Balenkova, E.S J Org Chem USSR1988, 24, 1447