Organic syntheses based on name reactions a practical guide to 750 transformations a hassner and i namboothiri (auth )

Acetylenes, Allenes: Bailey cycloadd; Bergman cycloarom; Berchtold enaminehomol; Brown alkyne isomeriz; Colvin synth via diazo; Cooper–Finkbeiner Mg propar-gyl; Corey–Fuchs synth from al

Organic Syntheses Based on

Name Reactions

Organic Syntheses Based

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Foreword by D Seebach

Organic Syntheses Based on Name Reactions

When studying chemistry at the Technische Hochschule Karlsruhe, more than 50 yearsago, we had to memorize close to 50 Name Reactions for the final examination in organic chem-istry The then one and only book on Name Reactions was Krauch-Kunz’s Reaktionen derOrganischen Chemie, which tried to be complete at the time In the mean time, synthetic organicmethodology has experienced an explosive expansion, which is due to two fundamentally dif-ferent types of developments: (i) theclassical reactions have been modified to become regio-,diastereo-, and enantioselective, and to become catalytic (cf organocatalysis) (ii) The—mostlycatalytic—use of transition-metal derivatives has enriched organic synthesis with new types

of reactions (cf metathesis), which can almost all be rendered enantioselective by employingchiral ligands on the metal centers Many of the resulting procedures for carrying out certaintransformations have turned out to be of broad scope and to be generally reliable, so that—forbrevity—they were named after their inventor(s) in synthetic discussions, and that’s all aboutName Reactions It is, therefore, not surprising that several monographs on this subject haveappeared and that new editions of books on Name Reactions are essential

This book first appeared in 1994, a second edition in 2002, and now the third one in 2011,with the number of Name Reactions covered increasing from ca 450 to 550 to over 700, and thenumber of cited papers from 2100 to 3300 to over 6000 Still, the size of the volume(s) remained

“manageable.” Of course, the authors had to make, with a personal bias, decisions about whichreactions to include and which to replace (an evolutionary process!) In fact, when browsingthrough the three editions, one can get the impression that they are quite different books, inspite of the commonunique features, which are, first of all, a typical specific experimental pro-cedure and a proposal of a mechanistic course for the covered Name Reaction Then, there areupdated references to most recent publications and cross-references to similar transformationswith a different name; the quality of theformulae has greatly improved; there are most usefulindices of names, reagents, reactions, abbreviations, and group transformations; last but notleast, there is a new, larger section entitled “An Overview of Synthesis-Related Name Reac-tion,” listing, for instance, all Name Reactions, in which aldol-type transformations; cycload-ditions; or S, Se, Si, Sn, Bi compounds are involved, to name only three of the 40 entries in thissection A scientific book without an excellent index for access to its content is not a good book;this one is, indeed, excellent, not least because of these indices!

I went through the pages of this third edition with great pleasure I learned about some formations, which were new to me To some extent, it was a learning experience like when Istudied a textbook as a student The book has, indeed, textbook character and could be used inlab courses as a “cook book” and in advanced organic chemistry courses for problem-solvingsessions and as a source of exam questions—without requesting that the students actually mem-orize the Name Reactions, as in the old days: to cover the fundamental reactivities of organiccompounds theymust learn names connected with some transformations, reagents, and mech-anisms On the other hand, a discussion between top synthetic organic chemists (cf specialists

trans-in total synthesis of complex natural products, “synthetic engtrans-ineers”), with a life-long ence, will inevitably be full of reference to Name Reactions; when the name “pops up,” there isimmediate mutual understanding and agreement that there is mention of a generally applicableand reliable chemical transformation.

experi-In our time of online data bases, such as Chemical Abstract’sScifinder, Beilstein/Gmelin’sReaxys (ReactionFlash), Houben-Weyl’s Science of Synthesis, or even Google and Wikipedia(I have successfully tested some of the more “fancy” Name Reactions therein), it is appropriate

to ask the question: “Who needs a book on Name Reactions?” The above-mentioneduniquefeatures of the third edition of Organic Syntheses Based on Name Reactions will make surethat many organic chemists in academia and in industry will want to have this book on theirshelves The success of the second edition and the call for a third edition are evidence for thisview Name Reactions are at the core of the art of organic synthesis!

Dieter SeebachETH Zu¨rich

Foreword by S Danishefsky

What’s in a Name Reaction?—A Lot

To my delight, I discovered that fascinating combination of rigor/hypothesis, hard-core ory/intuition, and commercial-level practicality/artistic elegance known as organic chemistry

the-in a 1954 course at Yeshiva University It was already clear that one of the challenges of Orgo(particularly for the pre-meds) would be the systemization of a huge body of factual data, allow-ing for retrieval of critical information at critical times (exams, etc.) Our official class textbookwas authored by Raymond Brewster at the University of Kansas However, the achievers in thecourse, whose ranks I sought to enter, also purchased a book written by Louis and Mary Fieser atHarvard Though these two tomes actually covered a very similar body of chemistry, there weresome notable differences in style Brewster attempted to rationalize the seemingly unmanage-able collection of facts in Orgo under what was then a newly emerging theoretical construct,encompassing mechanisms (still early days for “curved arrows”), effects of structure changes

on reactivity, and some of the then very new ideas regarding stereochemistry

The Fiesers, in turn, placed heavier emphasis on analogy arguments Fieser mechanisms inthose days tended to focus on proposed affinities between substrates and reactants with a highpremium on identifying likely leaving groups to be anticipated from various displacementsand condensations Much of this line of mechanistic conjecture was captured in a “lasso-type”presentation, wherein stable entities (cf.inter alia water, alcohols, amines, halides, etc.) wereextruded to drive otherwise mysterious processes forward

More so than Brewster, the Fiesers utilized the medium of Name Reactions to facilitate course The Name Reaction device in the Fiesers’ treatment tended to focus on overall reactionphenomenology (addition, elimination, aliphatic substitution, aromatic substitution, cycloaddi-tions, condensation, etc.) rather than on intimate goings on below the surface Thus, for in-stance, the Mannich Reaction would be seen as one which joined a secondary aminea to acarbonyl group (at that time almost always a ketone) through one linking carbon (usually form-aldehyde) by extrusion of water With the explosive growth of the number of valuable reactions

dis-in organic chemistry and with growdis-ing dis-insights dis-into mechanistic issues, the importance ofName Reactions grew The Name Reaction tended to embrace not only a transformation butalso a particular mechanistic idea As such, Name Reactions facilitated discussions of bothmechanism and synthesis Hence, the role of the Name Reaction classification in facilitatingdiscussion became central Two people, more or less on the same structural and mechanisticpages, could communicate a remarkable amount of information and even prospective ideasthrough the use of well-chosen Name Reaction descriptors Even today, I find Name Reactions

of increasingly great value in organizing my own thoughts about synthesis as well as nisms, and in sketching out, if qualitatively, the landscape of our science

mecha-In principle, it might have been argued that the need for this type of classification is ing in the face of powerful searching technology for canvassing large bodies of information,including structures, and even reaction types Surely no one could argue that, in this dayand age, the medium of the Name Reaction is the primary way of conveying descriptiveand mechanistic information However, the Name Reaction system is still a major aid in

decreas-classifying large amounts of information in digestible form As a classroom teacher, mastery ofthe key Name Reactions is high up on my list of charges to the class on day one of the course.Accordingly, I was very pleased to respond to the invitation of Professor Alfred Hassner tocomment on his emerging book, which updates, in a most valuable way, an increasing number

of Name Reactions Even 57 years after taking the course described above, I remain totally cited at the concept of the awesome power of chemical synthesis The notion that any structure(within reason!), of which the human mind can conceive, is a possible target for chemical syn-thesis remains to me one of the most noble ideas in the epistemology of science The time is longsince past when triumphs in synthesis are viewed primarily as personalized mountain climbingexercises The macho/bravado element is still there, as it is in all artistry-intensive human un-dertaking but is far less central Synthesis is really about the capacity of the human imaginationand human resourcefulness to find ways of joining molecules in a precise, disciplined way withhigh levels of control Many of these molecules are of immediate interest from a material sci-ence or pharmaceutical perspective Others are of interest as probes for evaluating hypotheses

ex-in structure theory or ex-in biological signal transduction cascades Aside from its ex-intrex-insic appeal

to the artistic impulse, synthesis plays an important role in human progress

The opportunity of dedicating one’s intellectual imagination to complex problems, many ofwhich are apt to serve the needs of a growingly needful society, must be seen as a great priv-ilege The means for codifying information, which is central in this regard, while rewarding theinitiators (even posthumously) of what becomes a Name Reaction retains its special culturalstatus in assisting the forward march of our science Name Reaction assignments have aboutthem a significant element of intellectual history However (and needless to say), the tracingback of all the antecedents of an idea is actually an endless process What Name Reactionsare really about is an agreed upon vocabulary,by convention, for communicating concepts

in concise but human terms, befitting one of the most esthetics-intensive of scientific activities,that is, organic synthesis

Not surprisingly, with the growing complexity and urgency of problems with which a entist is faced comes an increasing need for multidisciplinary ventures I would argue (thoughnot without an admittedly strong dose of field chauvinism) that the truly unique gift that chem-istry brings to such urgent collaborations is its aspiration for achieving unencumbered synthe-sis This expansiveness distinguishes chemical synthesis from the unbelievably powerful (morecircumscribed) engine of biosynthesis Melding the skill sets of biology-mediated synthesis andunencumbered chemical synthesis is one of the great opportunities at the chemistry/biologyfrontier

sci-While it is well to think about issues of abstract logic and strategy, and ways in which theyinfluence chemical synthesis, the actual drivers of the field are the huge advances in reactionfeasibility arising from fundamental studies of methodology and its enabling mechanisms Inshort, the often unsung heroes of the awesome triumphs in chemical synthesis are the subjects ofthese Name Reactions (not to speak of their students and postdocs!)

I am pleased to congratulate my friend and field colleague, Fred Hassner, and his coauthorIrishi Namboothiri They surely need have no doubt that this latest book on Name Reactionswill be read in a continuing way and with great pleasure by their fellow scientists/artists

Sam DanishefskyColumbia University

Preface to the Third Edition

The past 10 years, since the publication of the successful second edition ofOrganic SynthesesBased on Name Reactions, have witnessed a renaissance in organic synthesis; especially in thediscovery of new reagents and chiral catalysts that have spurned development of asymmetricsyntheses This has made possible the synthesis of a significant number of complex naturalproducts in an enantioselective manner In the process one continues to notice that many syn-thetic methods, reagents, and reactions are being referred to in the organic chemistry researchcommunity by the names of their discoverers or developers

The proliferation of published material in chemical journals has led to journal requirementsthat authors be more succinct in their publications (witness the fact of extensive SupplementalMaterial in many journals); hence one often sees procedures or methods referred to by Namerather than by lengthy explanations For the student of organic chemistry, there is the advantage

of mnemonic that some prefer

One of the comments on the second edition ofOrganic Syntheses Based on Name Reactionswas that we omitted some older and less utilized Name Reactions that had appeared in the firstedition Hence for the sake of being comprehensive, we decided to keep such Name Reactions

in this revision Further, we have added over 100 new Name Reactions, the choice of which, ofcourse, reflects our own bias, and for that we apologize

All reactions have been brought up to date by including recent references where available Ifpossible, we have consulted living authors about their Name Reaction In some cases, no recentreferences were found, and this may reflect the fact that more modern or simpler reactions arenow preferred

It appears that people hesitate to refer to reactions by name if they bear more than two or threenames This made it desirable to break up reactions such as Hunsdiecker–Borodin–Cristol–Firth–Kochi into the more natural Hunsdiecker (Ag salts of RCOOH), Cristol–Firth (HgOand RCOOH), and Kochi (Pb derivatives) Similarly, in some cases, we separated a Name Re-action from its asymmetric variant, such as the Michael addition or Diels–Alder reaction, inorder to avoid them being too cumbersome Even so, since there are now several asymmetriccatalysts known for the same reaction, lumping all together would be quite unwieldy Further,

we felt it was relevant to finally give credit to major contributions of chemists who developedsuch well-established reactions as free radical dehalogenation with Bu3SnH (now Kuivila–Beckwith) or carbodiimide coupling reagents (now Sheehan) Ionic liquids and their asymmet-ric version are also included It will be noticed that quite a few name reactions are related to wellknown reactions (Friedel–Crafts, aldol, Michael, Grignard) but are known by different names.Some reactions are often known by one name but can also be referred to by another name,and this we tried to reflect in the introductory statement by including the other names aswell; for instance, Grob Fragmentation also known as Grob–Eschenmoser, or FokinCu-catalyzed Click reaction also known as Fokin–Sharpless–Meldal, or Hunsdiecker alsoknown as Hunsdiecker–Borodin

There is always a big problem combining the chemistry described by the originator of aName Reaction with the chemistry developed later and further adjusting it into limited space

Obviously, after the original publication, the reaction has sometimes mutated to quite a ent animal.

differ-The Overview section is a new and very important feature to the third edition For instance,the Overview lists syntheses of olefins by CþC bond formation (over 16 Name Reactions) or byelimination (over 30 Names) This is not only useful for advanced organic chemistry students,but should be very valuable to the researcher as at a glance comparisons of related methods forsynthesis of particular functional groups are provided Details can then be found under thenames Other Overview sections include asymmetric syntheses, syntheses of amine, cyclopro-panes, 5- and 6-membered ring heterocyles and many more Of course this is not meant as atextbook and is limited to named reactions

In addition the last few years have seen a proliferation of Pd- (and other metal-) catalyzedcoupling reactions; in fact several Nobel prizes were awarded in this field We have thereforealso included a brief Overview of Pd catalyzed Name Reactions with a general reaction pathway.Wherever possible in the new edition, we have alluded to the mechanism of reactions (prob-able reaction pathway) by providing an intermediate or a description, yet leaving some freedomfor students to supplement details

We limited the coverage of reactions since we preferred to keep the size and the cost of thevolume manageable

The new addition maintains the successful format of providing important references (over6000); in each case, this includes one of the first references to the reaction and a review ref-erence (marked R) where available Asymmetric syntheses are marked with an * References

to books are generally not included Further, a brief example of an experimental procedure isprovided in most cases In the experimental, we often refer to “work up” which is usually meant

to include, where necessary, washing, drying, extraction, evaporation, and purification(chromatography)

Important features of this monograph are the indexes, which should be helpful to the reader:

A name index with cross references to multiple names

asymmet-We thank our families for their understanding during the extensive work on this book and aregrateful to Dr Simcha Meir, Prashant Pavashe, Sundaram Rajkumar, and Mamta Dadwal fortheir invaluable help in bringing this volume to fruition Mistakes often creep in and we aregreatly indebted to Dr Thomas Allmendinger and Mr Simon Allmendinger for checkingthe manuscript and suggesting corrections that had been overlooked We are very grateful toour editor Dr A Shell for constant encouragement, suggestions as well as proofreading Thismonograph is dedicated to the memory of Cyd Hassner and of our children Suzie, Douglas andErica

Alfred HassnerIrishi Namboothiri

Preface to the Second Edition

The success of the first edition of “Organic Syntheses Based on Name Reactions and UnnamedReactions” and the proliferation of new Name Reactions are the reason for this new revisededition It became obvious that many new reagents and reactions are being referred to in theorganic chemistry research community by their names Hence, in addition to over 170 new re-actions (previously referred to as Unnamed Reactions) in the first edition, we have included inthe second edition 157 new Name Reactions bringing the total to 545 However, we have elim-inated the term “Unnamed Reactions” from the title of the monograph, since these reactions arenow no longer unnamed Furthermore, we omitted some older and less utilized Name Reactionsthat appeared in the first edition but have included them in the Name Index, by providing ref-erence to the page number in the first edition (e.g Baudisch 1-27, refers to first edition, p.27).The new additions are all synthetically useful or not immediately obvious transformations

In choosing them, emphasis was placed on stereoselective or regioselective reagents or tions including asymmetric syntheses The latter are particularly timely with the recent NobelPrize in Chemistry awarded in this area

reac-Again we admit our own bias in choosing from the many interesting newer transformationsreported in the literature Where possible we have tried to consult with the Name Reactionmajor author We apologize if inadvertently important reactions were omitted

We have maintained the useful format of providing important references (over 3,300); ineach case this includes one of the first references to the reaction and a review reference whereavailable Furthermore, an example of an experimental procedure is provided

Important features of this monograph remain the indexes, which should be helpful to thereader:

A names index with cross references to multiple names;

Hence, the monograph should be of interest to chemists in industry and academia In fact thisformat has led to the monograph being adopted as a text in advanced organic chemistry courses

We thank our families for their understanding during the travail on this book and are grateful

to TEVA Pharmaceutical Co for their support

This monograph is dedicated to the memory of my dear wife Cyd (A.H.)

Alfred HassnerCarol Stumer

Preface to the First Edition

And these are the names

The above are the opening words of Exodus, the second book of the Pentateuch Already inancient times, names were important in association with events As organic chemistry devel-oped during the 20thcentury, researchers started associating synthetically useful reactions withthe names of discovers or developers of these reactions In many cases such names serve merely

as a mnemonic, to remember a reaction more easily; there are few chemistry undergraduateswho do not know what the Friedel-Crafts reaction is

In recent years there has been a proliferation of new reactions and reagents that have been souseful in organic synthesis that often people refer to them by name Many of these are stereo-selective or regioselective methods While the expert may know exactly what the Makosza vi-carious nucleophilic substitution, or the Meyers asymmetric synthesis refers to, many students

as well as researchers would appreciate guidance regarding such “Name Reactions”

It is in this context that we perceived the necessity to incorporate the older name reactionswith some newer name reactions or “unnamed reactions”, that are often associated with a namebut for which details, references and experimental details are not at everyone’s fingertips Thiswas our inspiration for the current monograph“Organic Syntheses Based on Name Reactionsand Unnamed Reactions”

In particular, we thought it would be useful to include cross-references of functional grouptransformations and an experimental procedure, so that the reader will be able to evaluate thereaction conditions at a glance; for instance, is this reaction carried out at room temperature or at

200C? For 1 h or 5 days? Are special catalysts required? How is the reaction worked up, whatyield can be expected?

The choice of which reactions to include is not an easy one First there are the well known

“Name Reactions”, that have appeared in various monographs or in the old Merck index Some

of these are so obvious mechanistically to the modern organic chemistry practitioner that wehave in fact omitted them; for instance, esterification of alcohols with acid chlorides – theScho¨tten-Baumann procedure Others are so important and so well entrenched by name, likethe Baeyer-Villiger ketone oxidation, that it is impossible to ignore them In general, we havekept older name reactions that are not obvious at first glance

In some cases we have combined similar reactions under one heading, for instance, theHunsdiecker-Borodin-Cristol-Firth decarboxylative bromination It is not a simple task to de-cide whether credit is due to the first discoverer of a reaction or to its developers Often an im-provement on a method is more useful than the original discovery, and usually one reactionowes its inception to some previous discovery;non nova sed nove

Except in the case of reactions that have been known for a long time under shared names, weoften took the liberty to include in the title, as well as in the references (here to save space), onlythe name of the major author; for this we apologize to the co-authors, whose contributions areoften seminal For reactions named after contemporary authors, we have tried to consult theauthors about choice of examples, etc This led, for instance, to the Mannich-Eschenmosermethylenation

Among the newer reactions, we have chosen those that are not only synthetically useful,but, at first glance, not immediately obvious transformations Another criterion was the stereo-chemical implication of the process Yet, we admit our own bias in choosing from the plethora

of novel transformations that have appeared in the literature over the past 30 years or so Spacelimitation was by necessity a criterion Nevertheless, we have included approximately 450name reactions and 2100 references We sincerely apologize if we have inadvertently omittedimportant reactions

In all cases we have tried to include the first reported reference, a reference to an tal procedure, and whenever possible, a review reference (journal orOrganic Reactions) Ingeneral, we did not include references to books, series of monographs, or toOrganic Syntheses;chemists will of course consult these where available

experimen-Furthermore, we have compiled four indices, which should be helpful to the reader:

1 A names index with cross references to multiple names;

We are grateful to the TEVA Pharmaceutical Co for support of this project

Alfred HassnerCarol Stumerxvi Preface to the First Edition

This section lists all the name reactions according to the type of reaction, substrate involved orproduct formed in the reaction.

Overview Sections: Acetylenes, allenes•Aldols•Aldol-type•Amines and N-derivatives•

Amino acid, peptide•Asymmetric reactions•Boron compounds•C-Alkylation, acylation•

Coupling C–C (Pd cat)•Coupling C–C (cat by other metals)•Coupling C–C miscellaneous•

Coupling C¼O or C¼N with nucleophiles•Cyclizations (excludes heterocycles)•ditions•Cyclopropane synthesis•Cyclopropane reactions•Epoxides•Fluorine compounds•

Cycload-Free radical reactions•Halogen compounds except F•Hydrogenation catalytic•cles synthesis 5-rings•Heterocycle of other 5-rings•N-Heterocycles synthesis 6-rings•Het-erocycles of other 6-rings•Heterocycles miscellaneous•Multicomponent reactions•Olefinsvia Cþ C•Olefins via elimination•Oxidations•P, As-Compounds•Photochemical reac-tions •Rearrangements•Rearrangements Sigmatropic•Reductions (excluding Pd catalytichydrogenation)•S-, Se-, Si- Sn-Compounds•Sugars, carbohydrates, nucleosides•Thermalreactions

N-Heterocy-Abbreviations Used:AA¼ amino acid; acac ¼ acetoacetate; add ¼ addition; alc ¼ alcohol;alkyl ¼ alkylation; aldeh ¼ aldehyde; arom ¼ aromatic, aromatization; asym ¼ asymmetric;cat¼ catalyst, catalytic; cleav ¼ cleavage; cond ¼condensation; cpds ¼ compounds; cyc ¼ cycli-zation; cycloadd¼ cycloaddition; degrade ¼ degradation; D–A ¼ Diels–Alder; epox ¼ epoxida-tion, epoxide; equiv¼ equivalent; homol ¼ homologation; oxid ¼ oxidation; Pyr ¼ pyridine; rad ¼free radical; reag¼ reagent; rearr ¼ rearrangement; red ¼ reduction; rx ¼ reaction; sol ¼ soluble;synth¼ synthesis; w ¼ with

Acetylenes, Allenes: Bailey (cycloadd); Bergman (cycloarom); Berchtold (enaminehomol); Brown (alkyne isomeriz); Colvin (synth via diazo); Cooper–Finkbeiner (Mg propar-gyl); Corey–Fuchs (synth from aldeh); Crabbe (allene synth); Doering–La Flamme (allenes);Doetz (quinones from carbenes); Fokin (click, Cu cat); Fritsch–Buttenberg (alkyne synth);Glaser–Sondheimer (alkyne coupling); Johnson (alkyne synth via F); Kinugasa (cycloadd);Moore (cylobutenone coupling); Myers–Saito (cycloarom); Nicholas (propargyl alkyl Co);Ohira–Bestmann (alkynes from aldeh); Pauson–Khand (Co cat CO rx); Reppe (acetyleneoligomer); Robinson (Michael–aldol annulation); Skattebol (allenes); Srebnik–Quntar(cycloprop phosphonate); Stephen–Castro (cyclophane synth); Toste (alkyne Au cat); Whiting(LAH red); Sonogashira (Pd, Cu coupling)

Aldol Reactions: Abiko–Masamune (asym aldol); Aldol (cond); Auwers (flavone synth);Baer–Fischer (amino sugars via NO2–aldol); Baeyer–Drewson (indoxyl synth); Brown (anti-aldol); Camps (quinolinone synth); Chan–Brassard (acac equiv); Claisen (ester þ ester);Claisen–Schmidt (ketone þ ald); Crimmins–Heathcock (anti-aldol); Enders (asym SAMP);Erlenmeyer–Plochl (AA via hydantoin); Dieckmann (esterþ ester cyclization); Eschenmoser(methylenation); Evans (chiral auxiliary); Evans–Mukaiyama (asym aldol); Fujimoto–Beleau(ketoneþ ketone); Friedlander (quinoline synth); Gold (aminomethylation); Hagemann ester(cyclohexenone synth); Hajos–Parrish (asym Michael–aldol); Hanaoka–Wrobel (quinolizidinesynth); Henry (nitro aldol); Hiyama (amino acrylate synth); Houben–Hoesch (phenol

acylation); Kaiser–Johnson–Middleton (dinitrile cond); Lautens (aldol from vinylepoxides);List-Barbas (asym aldol); Mannich (ketone þ iminium); Meldrum (aldol); Morita–Baylis–Hillman (Michael–aldol); Mukaiyama (via Si enol ether); Ohira–Bestmann (alkyne from aldeh);Rauhut (Michael–Michael); Robinson (annulation via Michael–aldol); Scholtz (pyridinyl ketone

þ aldehyde); Stobbe (succinic acid þ aldeh); Weiss–Cook (diketone annulation); Wilkes–Armstrong (ionic liq, asym aldol); Wilkes–Rogers (ionic liq); Yamamoto (super Si double aldol);Yonemitsu (3-component); Zeiss–Hassner (ketone transposition; Ziegler (dinitrile cond).Aldol-type Reactions: Bally–Scholl (benzanthrone synth); Bouveault–Loquin (N¼O aldol);Chichibabin (indolizidine synth); Claisen (esterþ ester); Darzens epoxide synth); Dieckmann(cyclic Claisen); Doebner (malonic acidþ PhCH¼O); Duff (arom formylation); Ehrlich–Sachs(via nitroso); Feist–Benary (furan synth); Ferrier (chiral cyclohexanone synth); Franchimond(cyclobutanone synth); Garner (aldehyde rx); Gewald (aminothiophene synth); Gold (methylena-tion); Granacher (arylpropanoic acid synth); Hinsberg (thiophene synth); Krische (hydroxyalky-lation); Hagemann (acac to cyclohexenone); Hauser–Kraus (annulation); Hiyama (aminoacrylatesynth); Hooker (quinone rearr); Ivanov (Mg RCH2COOH alkyl); Knoevenagel (malonate þPhCH¼O); Mander (carbethoxylation); Marschalck (aromatic þ CH2¼O); Passerini (isonitrile

þ aldeh); Perkin (Ac2Oþ PhCH¼O); Pinhey (arylation Pb); Prelog–Stoll (acyloin cond); Rathke(b-ketoester synth); Reformatzky (Zn-ester þ ald); Roskamp (ketoester synth); Rovis–Enders(asym Stetter cat); Schoelkopf (AA synth); Soderquist (asym allylation B); Stobbe (succinic acid

þ PhCH¼O); Szarvasy (carbethoxylation); Takei–Casiraghi (siloxy heterocycle þ aldeh); meier (formylation); Williams–Ben–Ishai (AA synth); Wissner (HO-ketone synth); Wittig (ylide

Vils-þ aldehyde); Woodward (peptide synth); Zinke–Ziegler (calixarene synth)

Amine Synthesis (and N-Derivatives): Amadori (aminosugars synth); Angeli–Rimini(hydroxamic acid synth); Baer–Fischer (amino sugar synth); Beller (aniline synth Pd);Bertrand–Stephan (metal-free hydrogen via carbenes); Blum (aziridine synth); Borch (from

C¼O); von Braun (R3N degrad); Brown (via hydroboration); Bruylants (cyanoamine synth);Buchwald–Hartwig (N-aryl-, N-vinylamine Pd); Chichibabin (aminopyr synth); Curtius (fromRCOOH); Darapski (COOEt to NH2); Davis (N-oxide synth); Davis–Ellmann (chiral sulfini-mines); Delepine (RBr to amine); DeKimpe (aziridine, amidine synth); Dutt–Wormall (amine

to azide); Enders (asym synth); Eschweiler–Clark (amine methylation); Forster (diazo synth);Forster–Decker (sec amine via imines); Frankel–Shibasaki (allylamine to enamine); Gabriel(from alkyl halides); Garigipati (amidine synth); Girard (water sol hydrazones); Griess (deam-ination); Hassner (aziridine, azirine synth); Hesse–Schmid (Zip amine expansion); Hill–Barrett(cyclo hydroamination Ca cat); Hiyama (amino acrylate synth); Hoch–Campbell (aziridinesynth); Hofmann (amide degrad); Hofmann (isonitrile synth); Hofmann–Loeffler–Freytag(amine cycl); Hofmann–Martius–Reilly–Hickinbottom (aniline rearr); Japp–Klimgemann(hydrazone synth) Kabatchnik–Fields (aminophosphonate synth); Kaluza (isocyanate synth);Katritzky (amines by pyridinium displacement); Kreszge (allyl amination); Lehn (N,O-cryptants); Leuckart–Wallach (from C¼O); Lossen (hydroxamic to amine rearr); Mitsunobu(O- to N-displacement); Mori–Shibasaki (from C¼O Ti); Mundi (lactam to amine); Oleksyszyn(amino phosphonic acid synth); Olofson (t-amine dealkylation); Petasis (3-component synthB); Schweizer (allylamine synth); Schwartz (amine via hydrozirconation); Schwesinger(N, P bases); Sharpless (allyl amination); Sheverdina–Kocheshkov (amines from cuprates);Staudinger (via azide red); Stieglitz (N–Cl rearr); Strecker (AA synth); Suzuki (nitrile redCo); Trost–Hassner (from azides w Li, Mg); Voight (amino ketone synth); Wakamatsu(AA synth); Wasserman–Bormann (N-ring expansion); Wencker (aziridine synth); Zinner (hy-droxylamine synth); Zard (rad aminomethylation)

Amino acids, Peptides, Amides: Beller (AA synth Pd); Bouveault–Loquin (AA via N¼O);Bucherer–Bergs (AA via hydantoin); Darapski (cyanoacetate to AA); Erlenmeyer–Plochlxviii An Overview of Synthesis Related Name Reactions

(AA via hydantoin); Granacher (AA from thioketo acid); Herbst–Engel (AA by tion); Kabatchnik–Fields (aminophosphonate synth); Kagan–Horner–Knowles (AA from en-amines Rh); Hiyama (amino acrylate synth); Honzl–Rudinger (peptide synth); Kotha–Schoelkopf (AA from isocyanatoacetate); (Kowalski (b-AA from a-AA); Merrifield (via solidphase); Milstein (amide from alcohol); O’Donnell (asym AA via glycine); Oleksyszyn (aminophosphonic acid synth); Sanger (AA labeling); Schoelkopf (AA synth); Sheehan (EDC peptidecoupling); Staab (peptide via C¼O imidazole); Staudinger (via azide red); Strecker (AA synth);Ugi (diamides, AA); Wakamatsu (AA from acetamide Co); Woodward (peptide synth);Yamada (peptide synth).

transamina-Asymmetric Reactions (Excluding Hydrogenations): Abiko–Masamune (aldol);Abramov (OH-phosphonate synth); Alder (ene rx); Barbas (Michael); Brown (anti-aldol);Brown (allylation); Brown (functional group synth); Brown (ketone red); Corey (ketonered); Davies (Fe b-lactam auxiliary); Chan–Brassard (Si aldol); Corey (asym red); Crim-mins–Heathcock (aldol); Evans (chiral auxiliary); Davis–Ellmann (chiral sulfinimines); Dutha-ler–Hafner (allylation); Enders (SAMP); Evans (chiral aldol); Feringa–Pfaltz (asym Michael);Ferrier (cyclohexanone synth); Garner (chiral aldehyde rxs); Hajos–Parrish (Michael–aldol);Hassner–Ghera–Little (cyclopentanone synth); Hayashi–Uozumi (hydrosilation); Henry(nitro-aldol); Hoffman–Yamamoto (B allylation); Hoppe (allylation); Jacobsen (epox synthMn); Julia–Colonna (epox via polyAA); List (Mannich); List-Barbas (asym aldol); Kagan–Modena (sulfoxide synth); Katsuki (cyclopropane synth Zn, Al); Sharpless (epox Ti); Kinugasa(nitrile oxide cycloadd); List-Barbas (aldol); List-MacMillan (dihydropyridine C¼C hydroge-nation); Meldrum (aldol); Meyers (chiral oxazolines); Midland (propargyl ketone red); Mosher(chirality determination); Mukaiyama (aldol via Si enol ether); Oppolzer (allyl alc); Oppolzer(sultam); Pfaltz–Evans (bisoxazolines); Pfaltz–Feringa (asym Michael); Pirkle (resolution);Roskamp (ketoester synth); Rovis–Enders (Stetter rx w chiral heterocycl carbene); Schoelkopf(AA synth); Kotha–Schoelkopf (AA synth); Sharpless (dihydroxylation); Seebach (w chiraloxazolidones); Seebach–Beck (TADDOL cat rxs); Shibasaki (cat heterobimetallic); Soderquist(B-bicyclodecane); Stoltz (allylation); Strecker (AA synth); Takemoto (chiral thiourea cat);Vasella–Bernet (cylopentane synth); Wilkes–Armstrong (ionic liq, chiral imidazolium);Yamamoto (allylation); Yamamoto (allyl displacement)

Boron Compounds: Bertrand–Stephan (rx via carbenes); Brown (asymanti-aldol); Brown(asym allylation); Brown (asym ketone red); Brown (functional group synth); Brown (selectivered); Brown (ketone syn); Buchner–Curtius (homologation via carbene); Corey (asym red);Liebeskind (thioester coupling via B); Matteson (aldeh synth via boronic ester); Oppolzer(vinyl-B, Zn); Pasto–Matteson (B–C–Br rearr); Petasis (amine synth via B); Soderquist (bora-bicycles); Suzuki–Miyaura (Pd coupling via B); Zeisel–Prey (ether cleav w BBr3)

C-Alkylation, Acylation: Baeyer (diarylmethane); Balson (aromatic alkylation HþBlanc–Quellet (haloalkylation); Darzens–Nenitzescu (C¼C acylation); Eschenmoser (methy-lenation); Friedel–Crafts (alkylation, acylation); Fries (phenol ester rearr); Lebedev (methox-ymethylation); Mander (methoxycarbonylation); Mannich (b-aminoketone synth); Prins(hydroxymethylation); Rieche (arom formylation Ti); von Richter (arom carboxylation);Reimer–Tiemann (phenol formylation); Rosenmund–Braun (arom cyanation Cu); Rosini–Bartoli (nitroarene alkylation via Mg); Stork–Huenig (cyanohydrin rxs); Szarvasy–Schopf(methoxycarbonylation); Vilsmeier–Haack–Viehe (formylation); Yamazaki (arom cyanation);Zinke–Suhl (cyclohexadienone from phenol)

Coupling C–C Pd Catalyzed: Beller (AA synth); Fukuyama (thioester to ketone); Fujiwara(carboxylation); Heck–Fujiwara (alkeneþ arom); Hiyama–DeShong–Denmark (silane þ arylhalide); Kumada (via Mg); Larock (annulation); Liebeskind (thioesterþ borane); Negishi (via

Zn, Al); Oppolzer (Pd, CO); Sonogashira (acetylenes Cu); Stille (ketone synth); Stille–Milstein

(via Sn); Suzuki–Miyaura (via BR2); Trost (via trimethylenemethane); Tsuji–Trost (allylation);Yamamoto (imine allylation).

Coupling C–C Catalyzed by Other Metals: Barbas (asym Michael); Barbier (Mg Sc);Barton (Bi phenylation); Buchwald (Zr heterocycl); Burton (arom CF3Cu); Collman (R-Br

þ CO Fe); Davies (asym Michael Fe); DeMayo (2 þ 2 photo); Doetz (Cr–CO w alkyne); ler–Hafner (Ti allyl); Felkin (Mg ene); Feringa–Pfaltz (Cu–Zn asym Michael); Fuerstner (FeMg); Fujiwara (Yb, La); Fukuyama (Zn keto synth); Friedel–Crafts (alkylation, acylation Al,

Dutha-Sn, Ti); Gilman (via Li, Cu); Danheiser (w vinylsilane Ti); Gingras (triflate displace Sn); ser–Sondheimer (Cu alkyne coupling); Grubbs (alkene–alkene metathesis Ru); Hollemann(pinacol synth Mg Ti); Hoppe (allylation Ti); Kagan–Molander (R-I w C¼O or C¼C cyclSm); Kametani (RCH2NH2to CN Cu O2); Kauffmann (dimerization Cu); Keck (rad allylationSn); Knochel (via Cu Zn); Kochi (via Fe Mg); Kulinkovich (cyclopropanol synth Ti Mg);Krische (asym red coupling Rh, Ir); Ladenburg (pyr benzylation Cu); Larock (annulation Tl,Pd); Liepa (V cycl); Lipshutz (cuprate add); Luche (Zn allylation); Michael (add); McMurry(C¼O coupling Ti); Murahashi (Cu allylation); Nicholas (propargyl alkylation Co); Nugent–Rajanbabu (epox Ti); Oppolzer (cyclopentenone w CO Pd); Pauson–Khand (cyclopentenone

Gla-w CO Co); Hollemann Pinacol (pinacol synth Mg CpTi, Mg Ti); Pinhey (arylation Pb); Reetz(C¼O þ RTi); Reppe (acetylene Ni, Ti); Roelen (C¼C hydroformylation Co); Rosini–Bartoli(NO2–arenes Mg); Sakurai–Hosomi (allylation, Si, Ti); Schwarz (via hydrozirconation);Seebach–Beck (asym C¼O rx Ti, Mg); Soderquist (borabicycles); Srebnik–Quntar (cyclopropphosphonate synth Zr); Takei–Casiraghi (siloxy heterocycl coupling Ti);Taylor–Ireland(alcohol olefination Mn); Toste (acetylene rx Au); Ullmann (Ar–Ar Cu); Ullmann–Goldberg(aromatic Cu, Zn); Wolfram–Schoernig–Hansdorf (oxidative carboxymethylation); Wurtz(Na, Cu); Yamamoto (asym allyl displacement Cu)

Coupling C–C Reactions Miscellaneous: Alder (allylþ C¼O ene rx);Alder–Rickert(D–A);Alper (lactam from amine); Baeyer (diarylmethane Hþ); Baeyer–Villiger (arom tritylation);Balaban–Nenitzescu–Prail (pyrylium salt synth); Bally–Scholl (benzanthrone synth);Barbas (asym Michael); Bardhan–Sengupta (phenanthrene synth); Benary (formylation Mg);Berchtold (enamine homologation); Blanc–Quellet (haloalkylation); Blomquist (macrocyclesynth); Bodroux–Chichibabin (o-formate to aldeh Mg); Boger (thermal cyclopentene synth);Boger–Carboni (hetero D–A); Borsche–Beech (via arom diazonium); Bouveault (RLi formyla-tion); Braverman–Mislow–Evans (sulfoxide rearr); Brown (ketone synth via boranesþ CO);Brown (functional groups homologation via boranesþ S-ylides); Bruylants (allylamine synth);Buchner–Curtius (homologation via diazo Rh); Cargill (cyclobutenyl ketone rearr); Carroll(Claisen rearr); Chan (acyloxyacetate rearr); Claisen ([3,3] allyl enol ether rearr); Conia(C¼O olefin ene rx); Cooper–Finkbeiner (alkene hydromagnesiation); Cope (3,3 diene rearr);Darzens–Nenitzescu (C¼C acylation); Dakin–West (RCOOH þ Ac2O); Danheiser (cyclopentenesynth via C¼CSi); Danishefsky (cyclohexenone synth via D–A); Davis–Ellmann (asymsulfinimines); Demjanov (via alkyl diazonium); Dieckmann (ester–ester condens); Dowd (freerad); Duff (aldeh synth); Emmert (pyridine Al–Hg); Enders (aldol via SAMP); Eschenmoser(methylenation); Eschenmoser–Meerwein (acetamidation); Eschenmoser (episulfide contrac-tion); Feringa–Pfaltz (asym Michael); Frankland (Hg, Zn); Freeman (Li DBB); Favorski(a-haloketone rearr); Felkin (Mg ene); Fischer (indole); Fittig (pinacol rearr); Friedel–Crafts(arom alkyl acyl); Fries (phenol ester rearr); Freund–Gustavson (cylopropane synth Zn);Fritsch–Buttenberg (alkyne synth); Fuerstner (via Fe); Fugimoto–Belleau (keto aldol);Garst–Spencer (furan synth); Gassman (oxindole synth); Gattermann–Koch (arom carbonylation);Gilman (via cuprates); Glaser–Sondheimer–Chodkiewicz (acetylene coupling); Gold(methylenation); Gomberg–Bachmann–Graebe–Ulmann (via aryldiazonium); Grovenstein–Zimmermann (carbanion rear); Hafner (azulene synth); Hammick (pyridine alkylation);

xx An Overview of Synthesis Related Name Reactions

Hass–Bender (C–Br to C¼O); Hassner–Ghera (cyclopentanation); Hauser–Beak (o-alkylation);Hauser–Kraus (hydroquinones); Hoffman–Yamamoto (allylation, B, Sn); Hofmann–Martius(C–C via aniline rearr); Houben–Hoesch (phenol acylation); Ireland (allyl ester 3.3 rearr); Ivanov(via Grignard); Johnson (arom alkynylation F); Kauffmann (arene dimerization Cu); Kiliani–Fischer (sugar homolog); Knunyants (F-alkyl); Koch–Haaf (carbocation carboxylation); Kotha–Schoelkopf (AA via isonitriles); Kowalski (ester homolog); Kuivila–Beckwith (free rad C–Cformation); Kolbe (carboxylic acid electrolysis); Kolbe–Schmidt (salicylic acid synth); Liebig(benzylic acid rearr); Johnson–Claisen (allyl orthoacetate rearr); Ladenburg ((pyridine alkyl);Meisenheimer–Janovsky (arom acetone complex); Meldrum’s acid (aldol); Miller–Snyder (arylcyanides); Larock (annulation); Laszlo (via acid clay); Lebedev (methoxymethylation); Makosza(arom substitution); Moore (cylobutenone coupling); Morita–Baylis–Hillman (Michael–aldol);Mousseron–Fraisse–McCoy (cyclopropane from halo ester); Mundi (N-acyllactam rearr); Mura-hashi (allylic alkylation Cu); Nokami (allyl alkylation); Parham (Li cycl) Paterno–Buchi (2þ 2addn); Parnes (Me transfer); Pauson–Khand (CO, Co); Perkin (malonate in cycl); Pedersen (iminecoupling Nb); Prins–Kriewitz (olefin-carbocation); Pschorr (diazoniumþ arom); Rauhut–Currier(Michael–Michael); Reformatsky (via haloester Zn); Rosenmund–Braun (Cu, cyanide); Reimer–Tiemann (formylation); von Richter (aromatic acids syn); Rieche (formylation); Rovis–Enders(asym Michael); Sakurai (Si allylation); Scholl (Al polyaromatic); Seebach–Beck (TADDOLcat); Snieckus (o-alkylation); Soderquist (asym B-bicyclodecane); Stork–Hunig (cyanohydrin);Stork (enamine rxs); Stork (radical cycl); Stork–Hauser (aminonitriles); Story (macrocycle synth);Togni (trifluoromethyl); Torgov (enol allylation); Toste (Au catalyzed); Trost cyclopentanation;Vasella–Bernet (cycloaddn); Wakamatsu (AA); Wilkes–Rogers (ionic liq); Williams–Ben–Ishai(via enamide); Wolff (a-diazoketone rearr); Wilkes–Armstrong (ionic liq, D–A); Wolfram–Schoernik (carboxymethylation); Woodward (peptide); Yamada (peptide); Zard (radical amino-methylation); Ziegler (macrocycle); Zincke–Suhl (cyclohexadienone synth); Zinin (benzidinerearrangement).

Coupling of C¼O or C¼N with C-Nucleophiles: (see also aldol-type reactions) Bailey(diazabicyclooctanes synth); Barbier (in situ w Mg, In, Sc); Bargellini (3-component RCOOHsynth); Benzoin (condensation, Lapworth); Black (enol carbonate rearr); Blanc–Quellet (chlor-oalkylation); Bodroux–Chichibabin (aldehydes from o-formates); Borsche–Beech ArN2þ toArC¼O); Bouveault (arom formylation); Brown (anti-aldol); Bruylants (cyanoamine synth);Chichibabin (arylpyridine from aldehþ NH3); Collman (carbonylation, Fe); Colvin (alkynefrom ketone); Corey (epox from ketone); Corey–Fuchs (alkyne from aldeh P-ylide); Corey–Seebach (dithiane nucleophile); Dakin–West (COOH to (C¼O)Me); Darzens (epoxide fromaldehþ haloester); De Kimpe (aldeh to aziridine); Dondoni (aldeh homologation); Duff (aromaldeh from (CH2N)4); Duthaler–Hafner (allylation, Ti); Ehrlich–Sachs (aldeh via nitroso);Emmert (C¼O alkylation); Granacher (arylpropanoic acid); Freeman (Li DBB ketone alkyl);Fujiwara (ketone condens Yb); Gattermann–Koch (arom carbonylation); Gilman–Speeter(b-lactams synth); Gilman–van Ess (ketone synthesis); Girard (RNHNH2 reagent); Ghosez(cyclobutanone synth); Grignard (RMgXþ C¼O); Hayashi (ArCOOH rearr); Hiyama–Heath-cock (Cr allylation); Hoffman–Yamamoto (B allylation); Hoppe (asym carbamate allylation);Horner–Wasworth–Emmons (via phosphonates); Ivanov (Grignard from RCH2COOH);Kagan–Molander (Sm); Lapworth (benzoin synth); Kaiser–Johnson–Middleton (via dinitriles);Knoevenagel (cinnamic acid synth); List (asym Mannich); Luche (Zn allylation); Mander (car-bomethoxylation); Nagata (cyanohydrin synth Al); Ohira–Bestmann (acetylenes from diazo-phosphonate); Oppolzer (Zn asym); Passerini (with isocyanide); Pedersen (Nb with imines);Prelog–Stoll (acyloin); Reetz (selective alkyl Ti); Reformatzky–Blaise (Zn and halo ester);Seebach–Beck (TADDOL cat Grignard, aldol); Seebach–Corey (rx w dithiane); Seyferth (acyllithium); Seyferth–Colvin–Gilbert (via diazo); Speckamp ((acyliminium); Stetter (1,4-add);

Stiles–Sisti (RMg formylation); Stork (via enamine); Szarvasy–Schoepf (carbomethoxylation);Takai (olefination Zn); Taylor–Ireland (alcohol olefination P); van Leusen (cyanation);Weinreb (via amide Li); Widequist (halomalononitrile); Wissner (hydroxyketone synth);Wittig (olefination P).

Cyclizations, Excluding Heterocycles: Alder (ene); Barton (phenylation, Bi); Bergman(ene-diynes); Blomquist (macrocycle); Berchtold (enamine homologation); Bradsher (anthra-cene synth); Diels–Alder; Danishefsky (hetero Diels–Alder); Dieckmann (ester–ester cond);Conia (C¼O olefin ene rx); Cope (diene rearr); Danheiser (vinyl Si Ti); Doetz (hydroquinone);Elbs (polynuclear); Felkin (Mg ene); Franchimond (cyclobutanone synth); Grubbs (Ru olefinmetathesis); Hafner (azulene synth); Kaiser–Johnson (dinitrile); Kennedy (Re O-cycliz);Mascarelli (fluorenone synth); Parham (RLi); Pauson–Khand (cyclopentenone via CO);Prelog–Stoll (acyloin); Pschorr (diazonium þ arom); Robinson (Michael–aldol annulation);Stork (radical); Stork (reductive w Li–NH3); Story (macrocycle synth); Toste (alkyne Aucat); Wender (homo Diels–Alder); Zinke–Ziegler (calixarene synth); Scholl (polyaromatic);Ziegler (macrocycle)

Cycloadditions: Alder–Rickert (D–A); Bailey (criss-cross C¼O); Bergman zation); Bestmann (w P-ylides); Boeckelheide (heterocycl ring expansion); Boger (cyclopen-tane synth); Boger–Carboni (hetero D–A); Bradsher (isoquinolinium D–A); Brandi–Guarna(nitrile oxide, rearr); Fleming–Mah (anthracene synth 2þ 2); Fokin (alkyne þ azide click

(cycloaromati-rx, Cu cat); Danishefsky (hetero D–A); DeMayo (2 þ 2 photo); Diels–Alder; Diels–Alder(asym); Finegan (azide-nitrile); Fleming–Mah (benzyne 2þ 2); Ghosez (cyclobutanone synth);Hassner–Ghera–Little (methylenecyclopentane synth); Hetero Diels–Alder; Huisgen (dipolar);Kinugasa (nitrile oxide); Larock (vinylcyclopropane annulation); Myers (cycloarom); Paterno–Buechi (photo 2þ 2); Pfaltz–Evans (asym D–A); Staudinger (ketene); Trost (methylenecyclo-pentane synth; Wender (homologous D–A)

Cyclopropane Synthesis: Bertrand–Stephan (via carbenes); Boger (cyclopentane synth);Brandi–Guarna (spirocyclopropane rearr); Ciamician–Dennstedt (CCl2 addition); Cloke–Wilson (cyclopropyl ketone rearr); Doering–La Flamme (from allenes); Fischer (via carbene);Freund–Gustavson (from C–Br); Hassner–Ghera–Little (MIRC); Kagan–Molander (via Sm);Kulinkovich (cyclopropanol synth); Mousseron–Fraisse–McCoy (from halo ester); Nerdelfrom enol ether); Pfaltz–Evans (bisoxazolines); Pfau–Plattner (via diazo); Seyferth–Gilbert(via diazophosphonate); Seyferth (via dihalocarbene); Simmons–Smith (Zn, Sm carbene);Skattebol (from allenes); Srebnik–Quntar (cycloprop phosphonate); Toste (Au catalyzed);Wender (homologous D–A); Widequist (from halomalononitrile)

Cyclopropane rxs: Boger (thermal cyclopentene synth); Brandi–Guarna pane rearr); Ciamician–Dennstedt (dichlorocyclopropane); Cloke–Wilson (cyclopropyl ketonerearr); Doering–La Flamme (allenes from dihalocyclopropanes); Feldman (vinylcyclopropanerearr); Fischer (carbene); Favorski (haloketone rearr); Nerdel (ether homologation); Haller–Bauer (ketone cleavage); Kulinkovich (cyclopropanol synth); Skattebol (vinyl cyclopropanerearr); Simmons–Smith (Zn carbenoid); Wender (vinylcyclopropane D–A)

(spirocyclopro-Epoxides: Adler (spiro from phenols); Corey (epox from C¼O); Curci–Murray (via anes); Darzens (Zn from haloesters); Hassner–Rubottom (ketone hydroxylation via epoxides);Jacobsen (asym); Julia–Colonna (asym); Sharpless (asym); Lautens (vinylepoxide rx); Martin(dehydration); Payne (rearrangement); Sharpless (asymmetric synth)

dioxir-Fluorine Compounds: Burton (nucleophilic CF3); Comins (triflating reag); Gingras (OTf to

F via SnF); Johnson (arom alkynylation); Knunyants (F-alkyl); Mosher (chirality tion); Rozen (hypofluoride rxs); Ruppert (nucleophilic perfluoroalkylation); Schiemann(aromatic fluorination); Seyferth (difluorocarbene rx); Smith–Middleton–Rozen (C¼O fluori-nation); Swarts (Cl to F); Togni (electrophilic CF); Vorbruggen (OH to F)

determina-xxii An Overview of Synthesis Related Name Reactions

Free Radical Reactions: Barton (deamination); Barton (nitrite photo rx); Barton ylation); Barton–McCombie (via xanthate); Bergman (cycloarom); Cella–Piancatelli(IBX-TEMPO oxid); Chatgilaloglu (Si dehalogenation); Dowd (ring expansion); Feldman(vinylcyclopentane synth); Giese (C¼C additions); Jeger (THF synth); Keck (allylation);Kharash–Sosnovsky (oxidation, Cu); Kuivila–Beckwith (dehalogenation); Minisci (arom sub-stitution); Myers–Saito (cycloarom); Nugent–Rajanbabu (from epoxides Ti); Stork (rad cycl);Stork (red cycl); Suarez (hypervalent iodine rx); Treibs (allylic oxid); Wohl–Ziegler (bromina-tion); Zard (radical aminomethylation).

(decarbox-Halogen Except F: Appel (displacement via P); Barleunga (pyridine iodonium); Barton(decarboxylation); Blanc–Quellet (haloalkylation); Boord (Br enol ether); Brown (I, functionalgroup); Cella–Piancatelli (IBX OH-oxid); Chatgilialoglu (Si dehalogenation); Cristol–Firth(halodecarboxyl Hg); Feist–Benary (Br furan synth); Finkelstein–Gryszkiewicz (displacement

Br, Cl, F); Freund–Gustavson (Br, Cl cylopropane synth); Hassner (iodine azide); Hassner–Rubuttom (a-haloketones synth); Hell–Volhardt–Zelinski (a-halo acids); Hunsdiecker (halode-carboxylation); Julia–Bruylants (homoallyl synth); Keinan (red I); Kochi (halodecarboxyla-tion); Khun–Winterstein (alkene synth I); Kuivila–Beckwith (Bu3SnH dehalogenation);Lemieux–Johnson (IO4, diol oxid); Mukaiyama (lactonization halopyridinium); Nicolaou(IBX OH-oxid); Oshiro (Br red); Suarez (ROI); Stieglitz (chloroamine rearr); Varvoglis–Moriaty (hypervalent I); Vohl–Ziegler (bromination via NBS)

N-Heterocycle Synthesis 5-Rings: Asinger (thiazoline); Baeyer (oxindole); Baeyer–Drewson (indoxyl); Bailey (diazabicyclooctanes); Bamberger (imidazole); Bischler–Mohlau(indole); Boulton–Katritzky (oxadiazole rearr); Bredereck (imidazole); Bucherer–Bergs(hydantoin); Cadogan–Cameron–Wood (cycl via NO2); Chichibabin (indolizidine);Clauson–Kaas (pyrrole); Cornforth (oxazole); Davidson (oxazole); Dimroth (triazole);Dondoni (thiazole); Erlenmeyer–Plochl (AA via oxazolone); Finegan (tetrazole); Fischer–Borsche–Drexel (indole); Fischer (oxazole synth); Fokin (triazole, click rx): Gabriel–Heine(imidazoline); Gassman (oxindole); Gewald (aminothiophene, pyrrole); Groebke–Blackburn–Bienyame (imidazole); Hinsberg (thiophene); Hantsch (thiazole); Hassner (C¼C to tetrazole);Hassner–Ghera–Little (pyrrolines); Herz (benzothiazole); Hinsberg–Stolle (indole); Hofmann–Loeffler–Freytag (pyrrolidine); Huisgen (oxadiazole); Huisgen (zwitterions); Johnson (alkyne

to indole); Japp (oxazole); Kawase (oxazole rearr); Kennedy (THF); Knorr (pyrazole); Kohler(isoxazoline); Larock (indole); Leimgruber–Batcho (indole); List-MacMillan (imidazolium

C¼C hydrogenation); MacDonald (porphyrin); Madelund (indole); Meyers (asym oxazolinerxs); Neber–Bosset (oxindole); Nenitzescu (indole); Overman (pyrrolidine); Paal–Knorr (pyr-role); Padwa (pyrroline); von Pechman (pyrazoline); Pfaltz–Evans (bisoxazolines asym rxs);Pilloty–Robinson (indole); Reissert (indole); Robinson–Fould (indole); Robinson–Gabriel(oxazole); Rothemund–Lindsey (porphyrin); Sandmeyer (isatin); Schoellkopf–Barton–Zard(pyrrole); Scholtz (indolizine); Schweizer (pyrazole); Shibasaki (indole); Shibasaki (TiN-insertion); Staab (C¼O diimidazole); Traube (purine); Van Leusen (isonitrile); Wallach(imidazole); Watanabe (indole, Ru); Weidenhagen (imidazole); Wilkes–Armstrong (ionic liq,asym imidazolium); Wilkes–Armstrong (ionic liq, imidazolium); Yonemitsu (3-component in-dole synth); Zav’yalov (pyrrole)

Heterocycle Synthesis Other 5-Rings: Buchwald (Zr, heterocycl, also N); Feist–Benary(furan); Garst–Spencer (furan); Hinsberg (thiophene); Jeger (THF synth); McCormack–Kuchtin–Ramirez (phosphole); Mascarelli (benzofuran); Nikl (benzofuran); Perkin (benzofuran);Rapp–Stoermer (benzofuran); Vollhardt–Erdmann (thiophene); Jeger (tetrahydrofuran).N-Heterocycle Synthesis 6-Rings: Baeyer (pyridine); Bamberger (benzotriazine);Bernthsen (acridine); Biginelli (pyrimidone); Bischler (benzotriazine); Bischler–Napieralski(isoquinoline); Boeckelheide (pyridine); Boger–Carboni–Lindsey (hetero D–A); Blicke–

Pachter (pteridine); Bradsher (isoquinoline via D–A); Brandi–Guarna (pyridones from propane); Burgess (oxazine); Cadogan–Cameron–Wood (cycl via NO2); Camps (quinolinonesynth); Chichibabin (arylpyridine); Combes (quinoline); Corey–Nicolaou–Gerlach (lactonization

spirocyclo-w pyridinethiol); Doebner–Miller (quinoline); Emmert (pyridine alkyl); Gould–Jacobs lone); Grubbs (via Ru metathesis); Ferrario–Akermann (thiocyclization); Friedlander (quinoline);Gabriel–Colman (isoquinolines); Gastaldi (pyrazine); Guaresky–Thorpe (pyridine); Haddadin–Issidorides (quinoxaline); Hammick (pyridine alkylation); Hanaoka–Wrobel (quinolizidines);Hantsch (dihydropyridine); Hilbert–Johnson (nucleoside); Hofmann–Loeffler–Freytag (piperi-dine); Kaiser–Johnson–Middleton (pyridine etc); Koenig (benzoxazine); Knorr (quinoline);Ladenburg (pyridine benzylation); Lehmsted–Tanasescu (acridone); Leuckart–Pictet–Hubert(phenanthridine); List-MacMillan (dihydropyridine C¼C hydrogenation); Mukaiyama (lactoni-zation w halopyridinium); Meerwein (O-alkylation); Mukaiyama (lactonization w halopyridi-nium); Mundi (N-acyllactam rearr); Niementowski (quinazolone); Pfitzinger (quinoline);Pictet–Hubert–Gams (isoquinoline); Pomeranz–Fritsch–Schlitter–Muller (isoquinoline);Remfry–Hull (pyrimidine); Reisssert (cyano-isoquinolines); von Richter–Widman–Stoermer(cinnoline); Robinson–Fould (quinoline); Simchen (rearr to isoquinoline); Skraup (quinoline);Speckamp (N-rings); Stieglitz (haloamine rearr); Timmis (pteridine); Traube (purine);Ullmann–Fedvadjan (acridine); Ullmann–Horner (phenazine); Ullmann–La Torre (acridine);von Richter–Widman–Stoermer (cinnoline); Westphal (quinolizidine); Yamaguchi (lactonization

(quino-w DMAP Cl3PhCOCl); Yamazaki (pyrimidine); Yamazaki–Clausen (guanine)

Heterocycle Synthesis of Other 6-Rings: Achmatowicz (pyranone from furan); Auwers(flavone); Baker–Venkataraman (flavones); Balaban–Nenitzescu–Prail (pyrylium salts);Ferrario–Ackermann (phenothiazine); Hetero Diels–Alder (pyrans); Kabe (chromanone);Menzer (benzopyran); Mueller (thiochromone); von Pechmann (coumarin); Robinson–Allan–Kostanecki (chromone); von Pechman–Duisberg (coumarin)

Heterocycles (Miscellaneous): Abramov (oxazaphosphole); Allen–Millar–Trippett phinine); Alper (lactams); Blum (aziridine); Breckport (b-lactam); Davies (b-lactam); Davis(oxaziridine reag); DeKimpe (aziridine); Gabriel–Heine (aziridine); Gilman–Speeter (b-lactams);Graham (diaziridine); Hassner (azirine); Hesse–Schmid (Zip polyamines); Kaiser–Johnson–Middleton (via dinitriles); Hoch–Campbell (aziridine); Kinugasa (b-lactam); Lehn (N,O cryp-tand); McCormick–Kutchin–Ramirez (phosphole); Mukaiyama (lactone); Parham (cycl);Paterno–Buechi (oxetane); Pedersen (crown ethers); Scheiner (aziridine); Schmidt (azepine byrearr); Schmitz (diaziridine); Speckamp (acyliminium); Staudinger–Pfenninger (thiiranes);Wasserman–Bormann (macrocycl lactam); Wenker (aziridine)

(phos-Hydrogenation Catalytic: Bertrand–Stephan (metal free); Crabtree (Ir selective); Eckert(Co, Pd); Kagan–Horner–Knowles (Rh); Lindlar (Pd); List-MacMillan (metal free); Noyori(homogen hydrogenation Ru BINAP); Pearlman (Pd hydrogenolysis); Rosenmund (aldeh fromacid chloride Pd)

Multicomponent Reactions: Bargellini (RCOOH synth); Beller (AA, arom synth); nelli (pyrimidone synth); Chang pyrrole synthesis; Groebke–Blackburn–Bienyame (imidaz-ole); Hantzsch (dihydropyridine synth); List (asym Mannich); Kabatchnik–Fields(aminophosphonate); Mannich (b-aminoketone synth); Morita–Baylis–Hillman (hydroxy al-kene syn); Mueller (thiochromone synth); Passerini (acyloxy amides); Pauson–Khand (cyclo-pentenone); Petasis (amine synth B); Rauhut–Currier (Michael–Michael); Strecker (AA synth);Ugi (diamides, AA); Yonemitsu (3-component)

Bigi-Olefin Formation (via C+ C Except Pd C–C Coupling): Barton–Kellogg (via tones); Bestmann (via phosphocumulene); Boord (enol synth); Corey–Chan (alkylation of al-kynes); Eschenmoser (methylenation); Eschenmoser–Stoltz (via aziridinehydrazones); Goldxxiv An Overview of Synthesis Related Name Reactions

thioke-(methylenation); Grob–Eschenmoser (fragmentation); Grieco (via Se from ROH); Grubbs ene metathesis Ru); Hiyama (aminoacrylate); Horner–Wadsworth–Emmons (via phospho-nates); Julia–Lythgoe (via sulfones); Julia–Kocienski (via sulfones); Katritzky–Li (viabenzotriazoles); Knoevenagel (malonateþ PhCH¼O); Kocienski–Fugisawa (Cu substitution);Ramberg–Backlund–Paquette (SO2elimination); Reich–Krief (via Se from ROH); Robinson(cyclohexenone synth); Ruppe (from acetylenic alc); Saegusa (enone synth Pd); Shapiro (fromtosylhydrazones); Siegrist (stilbene synth); Skattebol (from dihalocyclopropanes); Takai (from

(di-C¼O Zn); Tschugaef (via xanthates); Wharton (from hydrazinone); Petasis (via Ti); Peterson(from silane þ C¼O); Still–Gennari (Z via trifluoroethyl phosphonates); Stork–Zhao(Z-iodoalkene synth); Takai–Nysted (from CH2X2 Zn–Ti); Taylor–Ireland (alc þ P-ylide);Tebbe–Grubbs (w Ti–Al); Wittig (via P-ylides)

Olefin Formation (via Elimination): Bamford–Stevens (from tosylhydrazone); Barton–McCombie (from dixanthate); Burgess (–H2O); Chugaev (via xanthates); Clive–Reich–Sharpless (from selenoxide); Concellon (Z-olefin synth); Cope–Mamloc–Wolfenstein (fromamine oxides); Corey–Winter–Eastwood (via dioxalanes); Crabee (allene synth); Doering–

La Flamme (allene synth); Garegg–Samuelson (from diols); Grob–Eschenmoser tion); Grieco (from ROH via Se); Grubbs (metathesis Ru); Hofmann (from ammonium salts);Julia–Bruylants (cycloprop carbinol rearr); Julia–Lythgoe (via sulfones); Julia–Kocienski (viasulfones); Knoevenagel (malonateþ PhCH¼O); Khun–Winterstein (from diol); Martin sulfur-ane (from ROH); Mattox–Kendall (dehydrohalogenation); Migita–Sano (quinodimethanesynth); Peterson (from Si, OH); Ramberg–Backlund–Paquette (SO2elimination OH); Robinson(cyclohexenone synth); Ruppe (from acetylenic alc); Saegusa (enone from ketone Pd); Shapiro(from tosylhydrazones); Siegrist (stilbene synth); Skattebol (from dihalocyclopropanes);Tschugaef (via xanthates); Wharton (via hydrazone); Whiting (diene synth)

(fragmenta-Oxidations: Achmatowicz (pyranone synth from furans); Adler (of phenols); Baeyer–Villiger (ketone to ester); Baudisch (nitrosophenol synth); Barbier–Wieland (ester chain deg-radation); Barluenga (pyridine iodonium); Boyland–Sims (aminophenol synth); Cannizzaro(oxid-red); Cella–Piancatelli (of alc w IBX-TEMPO); Cooper–Finkbeiner (C¼C oxidationvia Mg); Corey (ketone epoxidation); Corey (of alc by Cr PCC); Corey–Kim (of alc

w Me2S-NBS); Criegee (diol w Pb(OAc)4); Criegee (hydroperoxide rearr); Curci–Murray(w dioxirane); Davis (oxaziridine reag); Dakin (arom C¼O to phenol); Delepine (aldeh oxidAg); Dess–Martin (of alc by periodinane); Djerassi–Rylander (of ethers, amides Ru); Doering(of alc w pyr SO3); Doyle (Rh allyl oxid); Elbs (of aromatics w persulfate); Ehrlich–Sachs(arom Me to CH¼O); Etard (Me to CH¼O); Guilemonat–Sharpless (allylic); Harries (via ozon-ide); Hass–Bender (C–Br to C¼O); Hooker (quinine synth); Jacobsen (asym epox); Jones (ofalc w CrO3-Hþ); Julia–Colonna (asym epoxide synth); Kagan–Modena (sulfoxide synth);Kakis (oxid aryl rearr); Kametani (amine to nitrile); Kharash–Sosnovsky (allylic Cu); Konaka(Ni peroxide reag); Kornblum (ald from alkyl halide); Lemieux–Johnson (C¼C to diol); Ley–Griffith (of alc by perruthenate); Lieben (of Me–ketone w NaOCl); Miescher (chain degrada-tion); Milas (diol synth); Mukaiyama–Ueno (of diols, Sn); Nicolaou (OH-oxid by IBX); Oppe-nauer (of alc by Al(OiPr)3); Pfitzner–Moffat (of alc by DMSO-DCC); Pinnick (aldeh toRCOOH w NaClO2); Riley (w SeO2); Pfitzner–Moffat (of alc w DMSO); Sarett (of alc

w CrO3-pyr); Schenck (allylic); Sommelet (aldeh from alkyl halide); Spengler–Pfannenstiel(sugar); Story (macrocycle synth from ketones); Swern (oxid of alc by DMSO-(COCl)2);Tamao–Fleming (RSi to ROH); Taylor–Ireland (alc olefination); Teuber (quinone synth); Tra-hanovsky (of ethers CAN); Treibs (allylic); Uemura–Doyle (allylic Rh); Varvoglis–Moriarty(w DIB); Uemura–Doyle (allylic Rh); Vedejs (ketone hydroxylation Mo); Wacker–Tsuji(olefin Pd–O); Weerman (amide degradation); Wilkinson (w O Rh)

P, As Compounds: Abramov (OH-phosphonate); Allen–Millar–Trippett (phosphoniumrearr); Appel (displacement via P); Arbuzov–Michaelis (phosphonate synth); Atherton–Todd(phosphoramidate synth); Bart–Scheller (arsenylation); Bechamp (arsenylation); Bestmann(P-ylides); Clay–Kinnear (P–Cl synth); Erlenmeyer–Plochl (AA P); Kabatchnik–Fields (ami-nophosphonate); Mann (ether dealkylation by phosphide); McCormick–Kutchin–Ramirez(phosphole); Michaelis–Nylen (phosphonate); Ohira–Bestmann (synth via P-ylide); Oleksys-zyn (amino phosphonic acid); Perkow (vinyl phosphonate); Pudovik (OH-phosphonate);Rauhut (Michael–Michael); Rosenmund (arsenylation of ArBr); Srebnik–Quntar (cyclopropphosphonate); Taylor–Ireland (alc olefination w P-ylide); van Boom (phosphorylation);Schwesinger (N, P base); Seyferth–Gilbert (diazophosphonate); Wilkes–Rogers (P ionicliq); Wissner (OH-ketone synth).

Photochemical Reactions: Barton (nitrite); Chatgilialoglu (rad Si); Ciamician (coupling);

De Mayo (2þ 2 cycloadd of alkenes); Moore–Danheiser (alkenylcylobutenone rearr); Paterno–Buechi (2 þ 2 cycloadd of C¼O); Suarez (of hypoiodide); Wolfram–Schoernig–Hansdorf(carboxymethylation)

Rearrangements: Achmatowicz (furan to pyranone rear); Acyloin (OSi rearr); Allen–Millar–Trippett (phosphonium); Amadori (aminosugars); Baker–Venkataraman (ketoester toflavones); Arndt–Eistert (diazoketone to ketene); Auwers (dienone to phenol); Black (enol car-bonate rearr); Boulton–Katritzky (oxadiazole); Brandi–Guarna (pyridones from spirocyclopro-pane); Brook (Si–ketone rearr); Bradsher (isoquinoline via cations); Brandi–Guarna (nitrileoxide cycloadd); Cargill (cyclobutenyl ketone rearr); Carroll (allyl ketoester rearr); Chan (acy-loxyacetate rearr); Chapman (O to N rearr); Cloke–Wilson (cyclopropyl ketone rearr); Colvin(alkynes via carbenes); Cornforth (oxazole rearr); Criegee (hydroperoxide rearr); Curtius(amine from acyl azide); Demjanov (via diazonium); Dimroth (N-R rearr); Ferrier (carbohrearr); Fischer (indole synth); Fittig (pinacol); Fries (phenol ester); Fritsch–Buttenberg (alkynesynth); Gabriel–Colman (phthalimide rearr); Grovenstein–Zimmermann (carbanion rearr);Gabriel–Heine (acylaziridine); Garst–Spencer (vinylepoxide); Hayashi (o-benzoylbenzoic);Hofmann–Martius (of anilines); Hooker (quinone rearr); Huisgen (tetrazole); Johnson (alkynesynth); Johnson–Claisen (allyl orthoacetate rearr); Julia–Bruylants (cycloprop carbinol);Kinugasa (asym cycloadd); Kakis (oxid aryl rearr); Kawase (acyl rearr); Koch–Haaf (carbox-ylation); Kreszge (S amination); Liebig (benzylic acid synth); Lossen (hydroxamic acid toamine); Meinwald (epox rearr); Meyer–Schuster (propargyl); Morin (S¼O rearr); Moore–Danheiser (alkenylcylobutenone rearr); Mundi (N-acyllactam); Overman (O to N allyl);Pummerer (S¼O); Schmidt (azide rearr); Simchen (N-heterocycl); Sommelet (ammonium);Stephens (ammonium); Steglitz (via nitrene); van Leusen (isonitrile þ C¼O); Wagner–Meerwein (carbocation); Wallach (azoxybenzene); Wessely–Moser (hydroxyxanthone);Westphalen–Letree (carbocation); Willgerodt (thioamide rearr); Zinin (benzidine rearr).Rearrangements Sigmatropic: Alder (ene rx); Carroll ([3,3] allyl acetoacetates); Claisen([3,3] allyl enol ethers, also thia, aza); Conia (1,5-ene cyclization); Cope (3,3 1,5-dienes);Eschenmoser–Meerwein (3,3 allylic N,O-ketene acetals); Felkin (Mg-ene cyclization);Frankel–Shibasaki (1,5-H); Fries (phenol esters); Guilemonat–Sharpless (allylic oxid); Ireland(3,3 silyl enolate of allyl esters); Johnson (3,3 allyl orthoacetates); Kirmse–Doyle (allyl sul-fide); Kreszge (S amination); Meisenheimer (N-oxide); Mislow–Braverman–Evans (2,3 allyl-sulfoxide); Newman–Kwart (thiophenol); Nokami (allyl alkylation); Overman (3,3 allyl O to Nrearr); Overman (3,3þ aldol aza-Cope–Mannich); Oxy-Cope (3,3); Reformatzky–Claisen (3,3allyla-bromoesters via Zn); Wittig (2,3 allyl ether)

Reductions (Excluding Pd Catalyzed Hydrogenation): Barton–McCombie ation); Birch (arom w Li–NH); Bischler (nitrophenylhydrazine red); Bertrand–Stephanxxvi An Overview of Synthesis Related Name Reactions

(deoxygen-(hydrogenation); Borch (ketone to amine); Bouveault–Blanc (w Na–ROH); Bouveault–Loquin(Ni N¼O red); Brown (asym ketone red); Brown (C¼O red agents); Caglioti (C¼O red);Cannizzaro (oxidation-reduction); Chatgilialoglu (w silanes); Clemmensen (Zn, C¼O red); Co-rey (asym B); Corey–Chan (propargyl LAH); Emmert (pyridine–ketone cond); Evans (1,3-anti-diol synth); Fujiwara (w Yb, La); Hassner (azirine to aziridine); Henbest (w Ir); Keinan(w diiodosilane); Kursanov–Parnes (w SiH); Leuckart (ketone to amine); List-MacMillan(C¼C hydrogenation w dihydropyridine); Luche (C¼O red Ce); McFadyen–Stevens (RCOOEt

! RCH¼O); Meerwein–Ponndorf (w La(OiPr)3); Midland (asymmetric C¼O red); Minami(aldehyde to alc); Moore–Danheiser (alkenylcylobutenone rearr); Oshiro (C¼CBr by phos-phite); Reissert (ald synth); Rosenmund (Pd, aldeh from R(C¼O)–Cl); Staudinger (azidered); Stephen (Sn RCN to RCH¼O); Stryker (Cu conjugate red); Suzuki (RCN to amine);Tischenko–Claisen (OH-ketone red); Traube (w Cr(II)); Wenzel–Imamoto (La–Ni selectivehydrogenation); Wilkinson (Rh cat); Wolff–Kishner (C¼O to CH2w hydrazine)

S, Se, Si, Sn, Bi Compounds: Acyloin rearr (enolsilane); Barton (Bi phenylation); Barton(decarboxylation S); Brook (Si–C¼O rearr); Bucherer–Bergs (thiohydantoin rx); Chan–Brassard (Si aldol); Chatgilialoglu (SiH red agent); Clive–Reich–Sharpless (C¼C from selen-oxide); Commins (enol triflate synth); Corey–Nicolaou–Gerlach (pyr disulfide for lactoniza-tion); Danheiser (C¼C–Si annulation); David–Thieffry (Bi O-phenylation); Davis–Ellman(sulfinimines); Eschenmoser (C–S–C contraction); Flood (Si–Cl synth); Ferrario–Akermann(S insertion); Freudenberg–Schoenberg (thiophenol synth); Fukuyama (thioester coupl); Giese(Sn, rad); Gingras (ArSnF reag); Grieco (Se olefination); Guilemonat–Sharpless (allylic oxidSe); Hassner–Rubbottom (C¼O a-functionalization via enolsilane); Hayashi–Uozumi (hydro-silation); Hiyama–DeShong–Denmark (C–C coupling via Si Pd); Ireland (Si allyl ester rearr);Kagan–Modena (S oxid); Kahne (sugars via S¼O); Keinan (SiH red); Kirmse–Doyle (allylsul-fonium rearr); Koser (tosylation); Kreszge (S amination); Kuivila–Beckwith (dehalogen

w Bu3SnH); Kursanov–Parnes (SiH reag); Liebeskind (S-ester coupl); Lawesson (C¼S from

C¼O); Leuckart (thiophenol synth); Morin (S¼O rearr); Mueller (thiochromone synth);Mukaiyama (aldol via Si enol ether); Mukaiyama–Ueno (diol oxid, Sn); Newman–Kwart(thiophenol from phenol); Nishimura–Cristescu (Si nucleoside synth); Oppolzer (chiral sultam);Pinhey (B arylation); Pummerer (S¼O rearr); Seebach–Corey (S dithiane rxs); Staudinger–Pfenninger (thiiranedioxide synth); Stephen (CN red, SnCl2); Stille (Sn carbonylation);Stille–Milstein (Sn–Pd coupling); Takei–Casiraghi (siloxyheterocycle þ C¼O); Tamao–Fleming (R-Si to ROH); Vorbrueggen (nucleoside synth via Si); Willgerodt (thioamide rearr);Yamamoto (aldol via super Si); Zard (xanthate rad rx); Zeisel–Prey (Si ether cleav)

Sugars-Carbohydrates, Nucleosides: Amadori (aminosugars); Baer–Fischer (aminosugar); Ferrier (chiral cyclohexanone from sugar); Ferrier (carboh rearr); Hilbert–Johnson(nucleoside synth); Kahne (sugars via S¼O); Kiliani–Fischer (sugar homolog synth);Koenigs–Knorr (glucosidation synth); Nishimura–Cristescu (nucleoside synth); Purdie (sugarmethylation); Spengler–Pfannenstiel (sugar degradation); Suarez (hypervalent iodine andsugar); Vasella–Bernet (cylopentane synth from sugars); Vorbrueggen (nucleoside synth);Wohl–Weygand (sugar degradation)

Thermal Reactions: Bechamp (arsonylation); Boger (thermal cyclopentene synth);Brandi–Guarna (pyridones from spirocyclopropane); Bredereck (imidazole syn); Chapman(O to N rearr); Chugaev (xanthate elimin); Claisen (allyl vinyl ether rearr); Conia (cycl); Cope(diene rearr); Dakin–West (decarboxylation); Diels–Alder; Elbs (polynuclear synth); Finegan(azide-nitrile cycloadd); Freudenberg–Schoenberg (thiophenol synth); Gould–Jacobs (quino-lone); Hofmann (elim of ammonium salt); Krapcho (decarbethoxylation); Hunsdiecker (halo-decarboxyl); Roelen (Co, hydroformylation)

Overview - Pd Catalyzed C –C Coupling

Name ReactionsMost Pd catalyzed reactions appear to involve the following catalytic cycle

Pd(0)

R Xoxidative addition

R PdII X

R PdIIR¢

R¢Rreductiveelimination

R¢YX-Y

ligand exchange/

trans metallation/insertiontrans

R PdII

R¢cis

LL

LL

isomerization

Some examples of Pd catalyzed coupling, for details see respective name reactions

Beller: ArCH=O + RCO–NH2 + CO PdCl2 RCO–NH–CH(Ar)–CO2H

Fukuyama: RZnI + R¢(CO)–S–Et PdCl2 R–(C=O)–R ¢

Fujiwara: C=C + CO (or CO2) + (O) Pd(OAc)2 C=C–COOH

BuN + F –

Br +

Kumada–Corriu–Tamao: RX + R¢MgX R–R¢ Ni or Pd catalysis

Cl MeO

+ n-BuMgCl Pd (0) orNi (0) cat n-Bu

MeO

Liebeskind: Ar–CO–S–Et + Ar¢-B(OH)2 Ar–CO–Ar¢ Pd or Cu

Stille CO: RX + C=CSnR¢ 3 + CO R–CO–C=C

OTf + Bu3Sn Pd(0) cat

CuI, DIPEA

R Cl

Tsuji–Trost allylation: (soft carbanion and allyl ester or carbonate)

OOO

Yamamoto allylation: R–CH=NR¢ + C=C–C-SiR¢ (or Sn) R (C*–NR¢)–C–C=C

DET Diethyl tartarate

(DHQ)2Pyr Hydroquinidine-2,5-diphenyl-4,6-pyrimidinediyl diether(DHQD)2Pyr Hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl dietherDIBAL Diisobutylaluminium hydride

Diglyme Diethyleneglycol dimethyl ether

DMSO Dimethyl sulfoxide

DNPH 2,4-Dinitrophenylhydrazone

dppf Diphenylphosphinoferrocene

EA Ethyl acetate

EAA Ethyl acetoacetate

EDC Ethylene dichloride

IBD Iodobenzene diacetate

IBX 2-Iodoxybenzoic acid

Im Imidazole

Ipc2BH Diisopinocampheylborane

KAPA Potassium (3-amino)propylamide

KHMDS Potassium hexamethyldisilazane

LAH Lithium aluminium hydride

LDA Lithium diisopropyl amide

L-DOPA L-3,4-Dihydroxyphenylalanine

LiDBB Lithium 4,4-di-t-butylbiphenylide

LiHMDS Lithium hexamethyldisilazide

LTA Lead tetraacetate

LTMA Lithium trimethoxyaluminium hydride

MVK Methyl vinyl ketone

NaHMDS Sodium hexamethyldisilazide

PMA Phosphomolybdic acid

PPA Polyphosphoric acid

ppt precipitate

Pr Propyl

prim primary

PPTS Pyridiniump-toluenesulfonate

PTC Phase transfer catalyst

PTSA (TsOH) p-Toluenesulfonic acid

Py (Pyr) Pyridine

RedAl Sodium bis(2-methoxyethoxy)aluminium hydride

rt Room temperature

SAMP (S)-(-)-1-Amino-2-(methoxymethyl)pyrrolidinesat saturated

sec secondary

(S)-BINAPO 2-Diphenylphosphino-20-diphenylphosphinyl-1,10-binaphthalene

RAMP (R)-(þ)-1-Amino-2-(methoxymethyl)pyrrolidine

TBAB Tetrabutylammonium bromide

TBAF Tetrabutylammonium fluoride

TBHP t-Butyl hydroperoxide

TBS/TBDMS t-Butyldimethylsilyl

TEA Triethylamine

TEBAB Benzyl triethylammonium bromide

TEBAC Benzyl triethylammonium chloride

temp temperature

tert tertiary

TEMPO 2,2,6,6-Tetramethylpiperidine-1-oxyl

TFA Trifluoroacetic acid

TFAA Trifluoroacetic anhydride

Tol (PhMe) Toluyl (Toluene)

TPPO Triphenyphosphine oxide

Ts p-Toluenesulfonyl (Tosyl)

TTAB Tetradecyltrimethylammonium bromide

TTMSS Tris(trimethylsilyl)silane

UHP Urea-hydrogen peroxide

List of Abbreviations xxxiii

ABIKO–MASAMUNE Asymmetric Aldol Reaction

Asymmetric aldol reaction between propionate esters e.g 1 and aldehydes 2 using (þ) or () epinephrine (or norephedrine) as a chiral auxiliary; proceeds via ester boron enolates 4 Formation

nor-of preferentiallysyn3oranti2products depends on the bulkiness of alkyl in the dialkylboron triflate,

as well as on the chiral auxiliary, thetert amine and temp (lower temp favors kinetic anti product);the large dicyclohexylboron triflate 4 leads predominantly to anti products 3 via E-boron esterenolates, while dibutylboron triflate and DIPEA give moresyn aldols.10Double aldol reaction

of acetate esters is possible.6 Methoxyacetates give syn-glycolate derivatives with highselectivity.8Compare with Evans syn-aldol and Crimmins anti-aldol (via ketone enolates)

c-Hex2BOTf

Et3N, –78 oC R

O H

Bn MeO2S

Ph O

R OH

anti Selective aldol (3).5

To a solution of norepinephrine ester (1R, 2S)-1 (4.80 g, 10 mmol) (R1¼ Bn,

R2¼ Mes) in CH2Cl2(50 mL) in an oven-dried 500 mL flask under nitrogen was added via syringeTEA (3.40 mL, 24 mmol) A solution of dicyclohexylboron triflate (1.0 M in hexane, 22 mL) wasadded over 20 min at78C and stirring was continued for 30 min IBA 2 (R ¼ i

Pr, 1.08 mL,

12 mmol) was then added dropwise and the mixture was stirred at78C for 30 min and then brought

to r.t (1 h) After quenching with a pH 7 buffer (40 mL), MeOH (200 mL) and 30% H2O2(20 mL)were added slowly After stirring overnight at r.t and usual workup and evaporation a solid wasobtained which was crystallized from hexane (150 mL) to give crude 3 (4.4 g) Removal of cyclohex-anol from the mother liquor and chromatography provided an additional product (0.6 g) Crystalliza-tion from EA–hexane (1:5) afforded 4.77 g (87%) of pureanti (þ)-3

syn Aldol (3).5

As above, reaction of ester (1R, 2S)-1 (R1¼ Me, R2¼ octahydroanthracenyl(OHA),0.4 mmol) withn-Bu2BOTf (0.8 mmol) andiPr2NEt afforded 3-syn (98%)

A

ABRAMOV Asymmetric PhosphonylationStereoselective phosphonylation of aldehydes by means of chiral phosphoro diamidates 2 or withBINAP catalysts, leading to chiral hydroxyalkyl phosphonates 7.

N

NP

Me3SiOPh

4 2

POEt

OEtP(OEt)3

(S)-BINAPO

Diethyl hydroxybenzyl phosphonate (7).10Phosphite 6 (1.50 mmol) was added to benzaldehyde 5(1.0 mmol),iPr2NEt (1.50 mmol), and (S)-BINAPO (10 mol %) in DCM (4 mL) at 78C SiCl

4(0.75 M DCM solution, 2.0 mL) was added over 2 h with a syringe pump Water (4 mL, deionized),sat aq NaHCO3(10 mL), and EA (10 mL) were added, the mixture was stirred for 1 h and filteredthrough celite Extraction with EA (3  10 mL), usual workup, and chromatography (silica gel

15 g, hexane:acetone 2:1 and 1:1) gave 7 (73%, 35% ee)

2

ACHMATOWICZ Furanylcarbinol Rearrangement

Rearrangement of 2-hydroxyalkylfurans 1, 7 (or 2-aminoalkylfurans)4to pyranose derivatives

4, 8 (or to 7-membered rings) by reaction with Br222MeOH,1NBS,5m-CPBA4or TBHP-VO(acac)2.6Also by anodic oxidation in MeOH.2

O O

Cl HO

OM e O

OH O

a pale yellow oil Compound 7 (0.292 g, 2 mmol) was added to a solution of m-CPBA (0.344 g, 2 mmol)

in CH2Cl2(2 mL) at 0C and the mixture was stirred for 3 h till a ppt was formed The precipitatedm-chlorobenzoic acid was filtered and the filtrate was concentrated in vacuo to afford the crude productwhich was purified by flash chromatography over silica gel (n-hexane/EA 3:1) to afford 8 as a colorlessliquid, 70%

A

ACYLOIN RearrangementRearrangement of O-silylacyloins (a-siloxyketones) catalyzed by strong bases (e.g KHMDS2); occurs with silyl transfer (1Æ 4).

OSiMe2t Bu

O OSiMe 2tBu

OSiMe 2tBu SMe O

O

MeN O

O OSiMe 2tBu

SMe

azatricyclo[5.3.1.02,6]undec-9-ene-3,5,8-trione (4).7To a solution of 1 (2 mmol) in THF (10 mL)was added KHMDS 2 (15% in PhCH3, 4 mL, 3 mmol) at50C under Ar and the mixture was stirred

(1b,2S*,6S*,7b,11S*)-7,11-Di-t-butyldimethylsilyloxy-4-methyl-11-(methylsulfanyl)methyl-4-for 3h, then 3% HCl was added at 0C Workup and chromatography (silica gel, PhH/hexane) afforded

4 (64%), mp 187–189.5C

ADLER Phenol OxidationAlso known as Adler–Singh Oxidation of o-alkoxyphenols with sodium metaperiodate toafford 6,6-spiro-2,4-cyclohexadienones, e.g 2, 5 which dimerize spontaneously to a Diels–Alder adducts 3, 6

O O 1/2

4

1 Adler E Acta Chem Scand 1959 13 505

ALDER (Ene) ReactionThermal or Lewis acid catalyzed sigmatropic rearrangement with H-transfer and C22C bondformation 3, either inter or intramolecular, and with chiral induction 8

HEt

CO2MeOH

O

O

Me Ph

∗ O O

O

H

Methyl 2-hydroxy-2-carbomethoxy-4-E-heptenoate (3).5

2 (2.92 g, 20 mmol) and 1-pentene 1 (1.4 g,

20 mmol) in DCM were heated at 140C for 16 h Evaporation and distillation gave a fraction boiling

at 90–105C (0.5 torr) which was treated with 20 mL ether, worked up and distilled to afford 3 (62%).Diethyl (2-isopropenyl-4,4-dimethyl cyclopentyl)-1-malonate (5).7The catalyst was prepared bystirring 4 g LiClO4 in 20 mL Et2O with silica gel for 30 min, evaporated and dried the catalyst

at 150 ˚C, 0.1 torr for 24 h The catalyst (100 mg) was stirred with 4 (596 mg, 2 mmol) in 4 mLDCM for 5 h under Ar at r.t Filtration and evaporation afforded 5 in quantitative yield

A

ALDER–RICKERT Acetylene CycloadditionSynthesis of polysubstituted benzenes 5 via Diels–Alder reaction of cyclohexadienes, e.g 2with acetylenes 3, via bicyclooctadienes 4.

Cl E

Cl E

5, 53%

2, 79%4

Dimethyl 3-chloro-5-hydroxy-6-methyl-4-(2-propenyl)-phthalate (5) A solution of 2 (12 g,

47 mmol, prepared from cyclohexenone 1 with LDA and TMSCl at70C), and DMAD 3 (9 mL,

73 mmol) in xylene (45 mL) was heated at 70C for 2 h and then at 145C for 4 h Evaporation

of the solvent in vacuuo followed by routine work-up and silica gel chromatography afforded9.48 g of 5 (53%) as an oil

ALDOL ReactionsBase or acid activated condensation between aldehydes and/or ketones to afford ab-hydroxyaldehyde (aldol) orb-hydroxyketone (ketol) 4 First examples by Claisen2

and Schmidt.1action proceeds by attack of an enolate 2 (or an enol) as nucleophile on an aldehyde 3 or othercarbonyl compound or on an iminium ion Many base catalysts can be employed; the most com-mon bases leading to enolates are KOH, K2CO3, KCN, NaOAc, CaO, amines, KOtBu,KHMDS, LDA (at low temp affords preferentially kinetic enolate 2), Amberlite Acid catalystsinclude HCl, H2SO4, H3PO4, and Lewis acids like BF3, POCl3, ZnCl2, FeCl3, TiCl4, InCl3.Retroaldol reactions (4Æ 1 + 3) are possible E-enolates lead preferentially to anti aldol 6,while Z-enolates afford syn aldols 7, via 6-membered ring transition states Many aldol typereactions, depending on carbonyl nucleophile or electrophile substrate (e.g aldehyde, ketone,ester, amide, iminium ion), are known by name, e.g Claisen, Evans, Knoevenagel, Mannich,Mukaiyama, Stork etc, as well as corresponding asymmetric aldols.4–7

Re-6

O

N O

SMe Me Ph

1 (i) LDA- Cp2ZrCl2(ii) Cp2ZrCl2

2 PhCHO

O N O

SMe

Me Ph

OH

O N O

SMe

Me Ph

Cp2ZrCl2 (990 mg, 3.38 mmol) was added and the mixture was stirred at 78C for another

10 min PhCHO (158.2 mg, 1.490 mmol) in THF (3 mL) was added and the mixture was stirred at

78C for 30 min and quenched with 1N HCl After usual workup and concentration, the residue

obtained was purified by silica gel chromatography (hexanes:EA:DCM 12:1:1 and hexanes:EA10:1) to give the product as a mixture of 6 (major) and 7 in 98% yield

ALLEN Phosphonium RearrangementAlso known as Allen–Millar–Trippett Ring enlargement of cyclic phosphonium salts 2,5obtained by alkylation or acylation of cyclic phosphines 1, 4 in the presence of base

PR

H2O reflux

P

O

P Ph O H O

Ph

O Ph OH Ph

PhCOCl

A

9-Methyl-9,10-dihydro-9-phosphaphenanthrene-9-oxide (3).1The phosphonium salt 2 (R¼ Me,0.7 g, 1.5 mmol) in aq acetone containing KOH solution was heated to reflux for 2 h Extraction ofthe cold mixture with CHCl3, evaporation of the solvent and silica gel chromatography via elutionwith EA:EtOH (7:3) afforded 0.24 g, 71% of 3.

Hydroxyphosphine oxide (8).6Benzoyl chloride (10 g, 71.1 mmol) was added to 4 (7.53 g, 40 mmol)and Et3N (20 mL) in Et2O (300 mL) After 3 h stirring under reflux 5 was hydrolyzed with water(150 mL) for 2 h The precipitates thus formed were removed by filtration and the resulting filtrate driedover MgSO4 Evaporation of the solvent and recrystallization from PhCH3afforded 10.8 g of 8 (87%)

ALPER CarbonylationCarbonylation of cyclic amines 4, hydroformylation (CO22H2) of amino olefins 6,carbonylation of alkenyl epoxides8and allenyl alcohols10or amines catalyzed by metal (Pd,

Ru, Rh) complexes Also dimerisation is possible with aziridine

O

CO HRh(CO)(Ph3P)3NaBH4, 100 o C,

34 atm

N O

8

6 Alper H J Am Chem Soc 1992 114 7018

AMADORI Glucosamine RearrangementAcid catalyzed rearrangement of aldoses 1, 3 via N-aldoglycosides to aminoglycosides of ketoses

2, 4 in the presence of amines Apparently proceeds via ring opening (I), imine to enamine tomerization and re-ring closure of aminoketone (II) to 2

OH OH NH–PhMe

OH NHTol +

OH

HO HO

O NHTol

OH

O OH HO

SO3

OH OH

OH HO

O 3 S

CH2NH2R OH

1-Cyclohexylamino-1,6-dideoxy-a-D-tagatofuranose-6-C-sulfonic acid (4).10

Amberlite IR-120(Hþ) cation exchange resin was added to a solution of 3 (131 mg, 0.465 mmol) in water (2.5 mL)

up to pH 0–1 The resin was filtered and washed and the combined filtrate was brought to pH 6using cyclohexylamine and concentrated to dryness several times by co-evaporating with abs EtOH.Crystallization from H2O/EtOH 1:1 afforded 4, 150 mg (94%)

A

ANGELI–RIMINI Hydroxamic Acid SynthesisSynthesis of hydroxamic acids 5 from aldehydes 1 and N-sulfonylhydroxylamines 2; also used

as a color test for aldehydes

Cl

C-NHOH NaOMe

0–20 °C +

SO2Ph

Ar OH N O

p-Chlorobenzene hydroxamic acid (5).6

To an ice-cold solution ofN-hydroxybenzene sulfonamide 2(730 mg, 4.2 mmol) in MeOH was added dropwise NaOMe-MeOH solution (4.36 mL, 8.4 mmol,1.93 M).p-Chlorobenzaldehyde 1 (562 mg, 4 mmol) in MeOH (4 mL) was then added and the reactionmixture was warmed to r.t MeOH was removedin vacuo, the residue was dissolved in ether (200 mL)and the organic layer was extracted with 2M NaOH The aq layer was acidified with conc HCl andextracted with EA The solution was concentrated to give product 5 (68%)

APPEL Displacement ReagentFormed from Ph3P and CCl4(or CBr4) 1, a reagent for chlorine (also bromine or iodine) dis-placement of OH (2+1 to 3, often with inversion) or for dehydration of amides 6 to nitriles 7, or

in Beckmann rearrangement (8 to 9) Sometimes used in the presence of imidazole One canalso use Ph3P and NCS.14

trans-2-Chlorocyclohexanol (5).5

trans-1,2-Cyclohexanediol 4 (3.82 g, 33 mmol) was added to a tion of 1, prepared from Ph3P (9.86 g, 33 mmol) in anh CCl4(60 mL) and MeCN (20 mL) After 24 hreflux, 1.95 g of 5 (88%) was isolated Retention of configuration here is probably due to epoxideintermediate

solu-2-Cyano-adamantan-4,8-dione (7).2To a solution of 6 (600 mg, 2 mmol), Ph3P (786 mg, 3 mmol)and Et3N (202 mg, 2 mmol) in anh DCM (60 mL) was added CCl4(308 mg, 2 mmol) After 15 h re-flux, the solvent was removed by distillation and the residue was chromatographed on silica gel (100 g)(PE/Me2CO increasing the polarity) The product in Me2CO:H2O 1:1 (40 mL) and conc HCl (5 drops)was refluxed for 5 h Recrystallization from PE (bp 60–95C)/Me2CO afforded 168 mg of 7 (89%),

mp 255–257C

ARBUZOV Phosphonate SynthesisAlso known as Michaelis–Arbuzov Synthesis of phosphonates 8 by heating of alkyl halides 5with trialkyl phosphites Ni catalyzed conversion of aryl halides 3 to aryl phosphonates 4 byreaction with phosphites 1, via phosphite-Ni complex 2

NiCl2

[(EtO)3P]4Ni

PO(OEt)2I

CH2Ph

O

MeO

CH(Me)Ph MeO

(MeO)3P

110 o C

8, 98%10

6 5

(MeO)3P

P N O

CH2Ph

OMe

MeO

R O

Dimethyl (N-benzyl-N-(1-phenylethyl)carbamoyl)methylphosphonate (8).10

Phosphite 6 (0.725 g,0.69 mL, 5.85 mmol) and bromide 5 (0.65 g, 1.95 mmol) were heated at 110C for 5 h Volatile im-purities were removed in a Kugelrohr in vacuum and the residue was purified by flash chromatography(silica gel, EA/hexanes/MeOH) to afford 8 (98%)

A

1 Michaelis A Chem Ber 1898 31 1048

ARNDT–EISTERT RCOOH HomologationHomologation of carboxylic acids, e.g 1 to 4, via reaction of their acid chlorides withdiazomethane and subsequent thermal or photochemical Wolff-rearrangement of the interme-diate diazoketones 2 via trapping of ketenes 3 with nucleophiles Water leads to carboxylicacids 4, alcohols afford esters while amines produce amides Also ring enlargement of ketones(8 Æ 9/10), sometimes Lewis acid catalyzed Compare with Kowalski For conversion ofaldehydes to ketones see Schlotterbeck

CH2N2, Et3N

Et2O, 0 o C

CHN2O

PhCO2Ag, Et3N EtOH, heat

CO2Et

Ethyl 1-naphthylacetate (7).3Diazoketone 6 (7.85 g, 0.04 mol) in abs EtOH (25 mL) was refluxedand freshly prepared catalyst (0.5 mL) made by dissolving silver benzoate (0.5 g) in Et3N (5 mL) wasadded More catalyst (0.5 mL) was added to the black mixture till N2evolution stopped After the mix-ture was refluxed for 1 h, cooled, and filtered, the solvent was evaporated and 38 mL of ether wasadded After washing (10% Na2CO3, water, and brine) and drying, the organic layer was evaporated

in vacuum to afford ester 7 (84%)

12