Organocatalytic Mukaiyama Aldehyde Cross-Aldol Reactions

Significance

Organocatalytic Mukaiyama aldehyde cross-aldol reactions have been reported. Addition of tris(trimethylsilyl)silyl (TTMSS) enol ethers 1 to aldehydes in the presence of 0.05 mol% of triflimide or TTMSSNTf₂ provides products of type 2 in high yields. Chiral aldehydes afford­ Felkin adducts for nonchelating α-substituents, chelation products for chelating α-substitu­ents, and syn products for β-substituents. Silyl enol ether 1 derived from propionaldehyde gives good syn:anti ratios. In addition, the first cascade Mukaiyama aldol synthesis has been developed. The use of 2.2 equivalents of acetaldehyde silyl enol ether 3 provides 2:1 adducts 4 in good yields and high syn diastereoselectivities.