Synthesis of N-Acyl-N,O-Acetals from N-Aryl Amides and Acetals in the Presence of TMSOTf

Secondary amides undergo in situ silyl imidate formation mediated by TMSOTf and an amine base, followed by addition to acetal acceptors to provide N-acyl-N,O-acetals in good yields. An analogous, high-yielding reaction is observed with 2-mercaptothiazoline as the silyl imidate precursor. Competing reduction of the acetal to the corresponding methyl ether via transfer hydrogenation can be circumvented by the replacement of i-Pr2NEt with 2,6-lutidine under otherwise identical reaction conditions