A tandem reduction of primary amines, carbonyl compounds, CO2, and boranes catalyzed by in situ formed frustrated Lewis pairs

Abstract

2-Aminothiazole in combination with a borane−trimethylamine complex exhibits efficient catalytic activity for four-component reductive methylation of primary amines, carbonyl compounds, boranes, and CO₂ (1 atm) under metal-free conditions. A wide range of highly functionalized tertiary N-methylamines are efficiently synthesized in one pot. In particular, multicomponent reductive reactions involving less reactive ketones are realized for the first time. This protocol is also applicable to the gram-scale synthesis of butenafine and late-stage modifications of several drugs. Mechanistic studies and DFT calculations indicate that an intramolecular FLP-type catalyst is generated and serves as the key for CO₂ activation.