Sustainable Carbonyl Acetalization Enabled by Frustrated Ion-Pair under Mild Conditions.

Acetalization represents a fundamental transformation for the protection of carbonyls and functional-group interconversion in organic synthesis. Herein, we report a metal-free dehydrative acetalization of aldehydes and ketones, including isatins with alcohols enabled by a frustrated triarylcarbenium ion pair as the catalyst. The reactions proceeded under mild conditions, and a broad range of acetal products was obtained up to 98% yield with excellent functional-group tolerance, including the late-stage protection of complex pharmaceutical molecules. Moreover, this protocol demonstrated high efficiency at lower catalyst loading, and the acetalization was readily scalable through continuous-flow processing to the gram level. Mechanistic studies supported a probable SN1-type pathway mediated by this frustrated ion pair.