Catalytic Enantioselective Formation of C−C Bonds by Addition to Imines and Hydrazones: A Ten-Year Update

2. Essential Components: Earlier Developments 5449 2.1. Activated alkenes/alkynes 5450 2.1.1. Acyclic activated alkenes/ alkynes 5450 2.1.2. Cyclic activated alkenes 5451 2.2. Electrophiles 5451 2.3. Catalysts 5452 3. Essential Components: Recent Developments 5452 3.1. Activated Alkenes/Alkynes 5452 3.2. Electrophiles 5460 3.3. Catalysts 5477 4. Asymmetric Baylis-Hillman Reaction: Earlier Developments 5495

Recent contributions from the Baylis-Hillman reaction to organic chemistry.

2.3.3. Fluorinated Imines 7 2.3.4. Arylimino Acetates 8 2.3.5. In Situ Generated Iminium Ions 8 2.4. -Substituted Michael Acceptors 8 2.5. Formation of Unexpected Products 10 2.5.1. Reaction with Cyclic Enones 11 2.5.2. Reaction with Vinyl Ketones 11 2.5.3. Reaction with Acrolein 12 2.5.4. Reaction with Activated Allenes and Alkynes 12 2.5.5. Reaction of Salicyl N-Tosylimines 12 3. Stereoselective Synthesis 13 3.1. Use of Chiral Aldehydes 13 3.2. Use of Chiral Bases 13 3.3. Use of Chiral Phosphines 16 3.4. Use of a Chiral Sulfide 18 3.5. Use of an Organocatalyst Derived from BINOL 18 3.6. Use of a Chiral Ligand Derived from Thiourea 18 3.7. Use of Chiral Ionic Liquids 18 4. Alternative Access Pathways to -Aminocarbonyl Compounds 18

aza-Baylis−Hillman Reaction

Catalytic asymmetric synthesis has received considerable attention over the past few decades, becoming a highly dynamic area of chemical research with significant contributions to the field of organic synthesis. In the development of new catalysts, the concept of multifunctional catalysis described by Shibasaki and co-workers, namely, the combination of more than one functional group within a single molecule to activate the transformation, has proved a powerful strategy in the design of efficient transition metal-containing catalysts. A variety of reactions have since been addressed with multifunctional organocatalysts. One example is the Morita−Baylis−Hillman (MBH) reaction, in which a carbon−carbon bond is created between the α-position of an activated double-bond compound and a carbon electrophile. The seminal report on this reaction in 1972 described the prototypical couplings of (i) ethyl acrylate with acetaldehyde and (ii) acrylonitrile with acetaldehyde; the reaction is promoted by the conjugate ad...

Multifunctional Chiral Phosphine Organocatalysts in Catalytic Asymmetric Morita−Baylis−Hillman and Related Reactions

The development of asymmetric Morita-Baylis-Hillman (MBH) reactions has evolved dramatically over the past few years, parallel to the emerging concept of bifunctional organocatalysis. Whereas organocatalysis is starting to compete with metal-based catalysis in several important organic transformations, the MBH reaction belongs to a group of prototypical reactions in which organocatalysts already display superiority over their metal-based counterparts. This Minireview summarizes recent mechanistic insights and advances in the design and synthesis of small organic molecules for enantioselective MBH and aza-MBH reactions.

The Enantioselective Morita–Baylis–Hillman Reaction and Its Aza Counterpart

In the aza-Morita–BaylisHillman reaction of N-sulfonated imines (N-arylmethylidene-4-methylbenzenesulfonamides and others) with methyl vinyl ketone (MVK), we found that in the presence of a catalytic amount of the chiral phosphine Lewis bases (R)-(−)-6,6′-bis[tris(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silyl]-2′-(diphenylphosphanyl)-[1,1′]binaphthalenyl-2-ol LB2 and (R)-(−)-6,6′-(3,3,4,4,5, 5,6,6,7,7,8,8,8-tridecafluorooctyl) -2′-(diphenylphosphanyl)-[1,1′]binaphthalenyl-2-ol LB3 bearing two perfluoroalkane chains at 6,6′-positions of the naphthalene framework, the corresponding adducts could be obtained in good yields with good to high ee (52–95% ee) at room temperature (15 °C) or low temperature (−20 °C) in THF, respectively. LB3 is more effective in this reaction than the previously reported original chiral phosphine Lewis base (R)-(−)-2′-diphenylphosphanyl-[1,1′]binaphthalenyl-2-ol LB1.

Asymmetric aza-Morita-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone catalyzed by chiral phosphine lewis bases bearing perfluoroalkanes as pony tails

Wen-Dong Teng

Papers

Asymmetric aza-Morita-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone catalyzed by chiral phosphine lewis bases bearing perfluoroalkanes as pony tails