DielsAlder reaction

The 4+2cycloaddition of a conjugated diene and a dienophile (an alkene or alkyne), an electrocyclic reaction that involves the 4 πelectrons of the diene and 2 πelectrons of the dienophile. The driving force of the reaction is the formation of new σbonds, which are energetically more stable than the πbonds. In the case of an alkynyl dienophile, the initial adduct can still react as a dienophile if not too sterically hindered. In addition, either the diene or the dienophile can be substituted with cumulated double bonds, such as substituted allenes

Diels-Alder Reaction

The [4+2]-cycloaddition of a conjugated diene and a dienophile (an alkene or alkyne), an

electrocyclic reaction that involves the 4 π-electrons of the diene and 2 π-electrons of the

dienophile The driving force of the reaction is the formation of new σ-bonds, which are

energetically more stable than the π-bonds

In the case of an alkynyl dienophile, the initial adduct can still react as a dienophile if not too

sterically hindered In addition, either the diene or the dienophile can be substituted with cumulated double bonds, such as substituted allenes

With its broad scope and simplicity of operation, the Diels-Alder is the most powerful synthetic method for unsaturated six-membered rings

A variant is the hetero-Diels-Alder, in which either the diene or the dienophile contains a

heteroatom, most often nitrogen or oxygen This alternative constitutes a powerful synthesis of six-membered ring heterocycles

Mechanism

Overlap of the molecular orbitals (MOs) is required:

Overlap between the highest occupied MO of the diene (HOMO) and the lowest unoccupied MO of the dienophile (LUMO) is thermally allowed in the Diels Alder Reaction, provided the orbitals are

of similar energy The reaction is facilitated by electron-withdrawing groups on the dienophile, since this will lower the energy of the LUMO Good dienophiles often bear one or two of the following substituents: CHO, COR, COOR, CN, C=C, Ph, or halogen The diene component should

be as electron-rich as possible

There are “inverse demand” Diels Alder Reactions that involve the overlap of the HOMO of the dienophile with the unoccupied MO of the diene This alternative scenario for the reaction is

favored by electron-donating groups on the dienophile and an electron-poor diene

The reaction is diastereoselective

Cyclic dienes give stereoisomeric products The endo product is usually favored by kinetic control due to secondary orbital interactions

Recent Literature

Chiral Oxazaborolidine-Aluminum Bromide Complexes Are Unusually Powerful and Effective Catalysts for Enantioselective Diels-Alder Reactions

D Liu, E Canales, E J Corey, J Am Chem Soc., 2007, 129, 1498-1499

Diarylprolinol Silyl Ether as Catalyst of an exo-Selective, Enantioselective Diels-Alder Reaction

H Gotoh, Y Hayashi, Org Lett., 2007, 9, 2859-2862

Asymmetric Diels-Alder Reactions of α,β-Unsaturated Aldehydes Catalyzed by a Diarylprolinol Silyl Ether Salt in the Presence of Water

Y Hayashi, S Samanta, H Gotoh, H Ishikawa, Angew Chem Int Ed., 2008, 47, 6634-6637

Catalytic Enantioselective Diels-Alder Reaction via a Chiral Indium(III) Complex

Y.-Chua Teo, T.-P Loh, Org Lett., 2005, 7, 2539-2541

Design of Chiral N-Triflyl Phosphoramide as a Strong Chiral Brønsted Acid and Its Application to

Asymmetric Diels-Alder Reaction

D Nakashima, H Yamamoto, J Am Chem Soc., 2006, 128, 9626-9627

A Mild and Efficient Asymmetric Hetero-Diels-Alder Reaction of the Brassard Diene with

Aldehydes

Q Fan, L Lin, J Liu, Y Huang, X Feng, Eur J Org Chem., 2005, 3542-3552

DIANANE-Cr(III)-salen Complexes as Highly Enantioselective Catalysts for Hetero-Diels-Alder Reactions of Aldehydes with Dienes

A Berkessel, N Vogl, Eur J Org Chem., 2006, 5029-5035

Highly Selective Diels-Alder Reactions of Directly Connected Enyne Dienophiles

M Dai, D Sarlah, M Yu, S J Danishefsky, G O Jones, K N Houk, J Am Chem Soc., 2007,

129, 645-657

[AlCl3 + 2THF]: A New and Efficient Catalytic System for Diels-Alder Cycloaddition of α,β-Unsaturated Carbonyl Compounds under Solvent-Free Conditions

F Fringuelli, R Girotti, F Pizzo, L Vaccaro, Org Lett., 2006, 8, 2487-2489

Strong Counteranion Effects on the Catalytic Activity of Cationic Silicon Lewis Acids in

Mukaiyama Aldol and Diels-Alder Reactions

L.-B Han, C.-Q Zhao, J Org Chem., 2005, 70, 10121-10123

Synthesis of Dihydronaphthalenes via Aryne Diels-Alder Reactions: Scope and Diastereoselectivity

C Dockendorff, S Sahli, M Olsen, L Milhau, M Lautens, J Am Chem Soc., 2005, 127,

15028-15029

Imidazolinium salts as catalysts for the aza-Diels-Alder reaction

V Jurcik, R Wilhelm, Org Biomol Chem., 2005, 3, 239-244

Catalytic Asymmetric Inverse-Electron-Demand Diels-Alder Reaction of

N-Sulfonyl-1-Aza-1,3-Dienes

J Esquivias, R G Arrays, J C Carretero, J Am Chem Soc., 2007, 129, 1480-1481

Chiral Brønsted Acid-Catalyzed Inverse Electron-Demand Aza Diels-Alder Reaction

T Akiyama, H Morita, K Fuchibe, J Am Chem Soc., 2006, 128, 13070-13071