Aqueous Asymmetric Mukaiyama Aldol Reaction Catalyzed by Chiral Gallium Lewis Acid with Trost‐Type Semi‐Crown Ligands

The combination of Ga(OTf)3 with chiral semi-crown ligands (1a - e) generates highly effective chiral gallium Lewis acid catalysts for aqueous asym- metric aldol reactions of aromatic silyl enol ethers with aldehydes. Aligand-acceleration effect was ob- served. Water is essential for obtaining high diastereo- selectivity and enantioselectivity. The p-phenyl sub- stituent in aromatic silyl enol ether ( 2h ) plays an im- portant role and increases the enantioselectivity up to 95% ee. Although aliphatic silyl enol ethers provided low enantioselectivities and silylketene acetal is easily hydrolyzed in aqueous alcohol, the aldol reactions of silylketene thioacetal (12) with aldehydes in the pres- ence of gallium-Lewis acid catalysts give the b-hy- droxy thioester with reasonable yields and high dia- stereo- (up to 99 : 1) and enantioselectivities (up to 96% ee).