One-Pot Synthesis of α-Branched N-Acylamines via Titanium-Mediated Condensation of Amides, Aldehydes, and Organometallics

A three-component, titanium-mediated synthesis of α-branched N-acylamines from commercial or readily accessible amides, aldehydes, and organometallic reagents is reported. The transformation proceeds under mild reaction conditions and tolerates a variety of functional groups (including nitrile, carbamate, olefin, basic amine, furan, and other sensitive heteroaromatics) to generate a large umbrella of α-branched N-acylamine products in high yields. The operationally practical procedure enables the use of this method in parallel chemical synthesis, a valuable feature that can facilitate the screening of bioactive molecules by medicinal chemists.