Efficient Preparation of α-Ketoacetals

The Weinreb amides 2a,b were prepared from the alpha,alpha-dimethoxyacetic acids 1c,d. A number of representative nucleophilic additions (RMgX and RLi) on 2 afforded alpha-ketoacetals 3a-j in 70-99% yield. These compounds represent a versatile arrangement of functional groups of significant synthetic value, as demonstrated in the synthesis of (+/-)-salbutamol.