Direct Coupling of Arylacetonitriles and Primary Alcohols to α-Alkylated Arylacetamides with Complete Atom Economy Catalyzed by a Rhodium Complex-Triphenylphosphine-Potassium Hydroxide System

A direct synthesis of alpha-alkylated arylacetamides from arylacetonitriles and primary alcohols has been accomplished for the first time. In the presence of the rhodium complex [Rh(cod)Cl](2)/triphenylphosphine/potassium hydroxide system, the desired alpha-alkylated arylacetamides were obtained in 74-92% yield under microwave conditions. The experimental results in this paper are in sharp contrast with previous reports, where the coupling of arylacetonitriles and primary alcohols produced the alpha-alkylated arylacetonitriles. Mechanistic investigations show that arylacetonitriles are first alpha-alkylated with primary alcohols to produce alpha-alkylated arylacetonitriles, which are further hydrated with the water resulting from the alpha-alkylation step to produce alpha-alkylated arylacetamides. More importantly, this research shows the potential of developing completely atom-economical reactions that involve the hydrogen autotransfer (or hydrogen borrowing) process.