The Mukaiyama Aldol and Mukaiyama–Michael Reactions Promoted by Commercially Available Molecular Sieves

The Mukaiyama aldol reaction of silyl ketene acetals with aldehydes has been effected by using commercially available 4Å molecular sieves (4Å MS) as a promoter.Various silyl ketene acetals and silyl enol ethers have been shown to be effective nucleophiles for this reaction.For the first time, it has been found that 4Å MS can promote the Mukaiyama-Michael addition reactions of silyl ketene acetals to , -enones.The addition of silyl enol ethers and silyl ketene acetals to carbonyl compounds, commonly referred to as the Mukaiyama aldol reaction, 1 is well recognized as one of the most powerful tools for carbon-carbon bond formation.The Mukaiyama aldol reaction can be catalyzed either by Lewis acids through the activation of carbonyl compounds or by Lewis bases through the activation of silyl enol ethers and silyl ketene acetals. 2,3It has also been shown that the Mukaiyama aldol reaction could proceed without added catalysts in some highly polar solvents such as DMF, DMSO, ionic liquids, water, and 1,8-diazabicyclo[5.4.0]undec-7-ene. 4 Recently, 1 we reported a catalytic enantioselective Mukaiyama aldol reaction of aldehydes (2) and methyl acetate-derived trimethylsilyl ketene acetal (3a) with the use of Rh 2 (S-BPTPI) 4 (1), a dirhodium(II) carboxamidate complex that incorporates (S)-3-benzene-fused phthalimido-2-piperidinonate as chiral bridging ligands, as a chiral Lewis acid in the presence of 4Å molecular sieves (4Å MS) [eqn.(1)]. 5 Although high yields and enantioselectivities of up to 94% ee were observed with specific aldehydes such as benzyloxyacetaldehyde and electron-poor aromatic aldehydes, the use of most aldehydes such as benzaldehyde resulted in the production of racemic aldol adducts.Surprisingly, further studies to improve the scope and generality of this reaction revealed that 4Å MS could accelerate the Mukaiyama aldol reaction of silyl ketene acetal and benzaldehyde even more effectively than could dirhodium(II) catalyst † Dedicated to Professor Emeritus Akira Suzuki on the occasion of his 80th birthday.