Deaminative Addition of Alkylpyridinium Salt to Aldehyde

Here we show that a primary amine can engage in the nucleophilicaddition to an aldehyde to synthesize an alcohol following preactivationof the amine. The enabling reagent for this radical-polar crossoverprocess is CrCl2. This reaction is selective for aldehydesand compatible with numerous functional groups, which are not toleratedunder classical Grignard-type conditions. Complementary to the well-establishedimine synthesis, this deaminative alcohol synthesis can broadly expandthe chemical space constructed by aldehydes and amines.

Automated summary

This study demonstrates that a primary amine, when preactivated, can undergo nucleophilic addition to an aldehyde to form an alcohol. The key reagent for enabling this radical-polar crossover process is CrCl2. This reaction is highly selective for aldehydes and can tolerate numerous functional groups, which are typically incompatible with classical Grignard-type conditions. As a complementary approach to imine synthesis, this deaminative alcohol synthesis offers a broad expansion of chemical space accessible through aldehydes and amines.