Diastereoselective three-component synthesis of beta-amino carbonyl compounds using diazo compounds, boranes, and acyl imines under catalyst-free conditions

Abstract

Diazo compounds, boranes, and acyl imines undergo a three-component Mannich condensation reaction under catalyst-free conditions to give the anti β-amino carbonyl compounds in high diastereoselectivity. The reaction tolerates a variety of functional groups, and an asymmetric variant was achieved using the (−)-phenylmenthol as chiral auxiliary in good yield and selectivity. These β-amino carbonyl compounds are valuable intermediates, which can be transformed to many potential bioactive molecules.We gratefully acknowledge Philip N. Moquist for editorial review of the manuscript. Preliminary experiments were performed by Y.L. at Boston University. Completion of the work was accomplished under the direction of G.W. at the University of Science and Technology Beijing, China. S.E.S. and Y.L. gratefully acknowledge the NIH for support (NIGMS R01 GM078240). Y.L., J.Y., and G.W. thank the Innovative Foundation from China National Petroleum Corporation (Grant No. 2012D-5006-0504) for financial support. Y.L. also thanks the Beijing Natural Science Foundation (Grant No. 2144052) and China Postdoctoral Science Foundation (2013M540859) for financial support. (NIGMS R01 GM078240 - NIH; 2012D-5006-0504 - Innovative Foundation from China National Petroleum Corporation; 2144052 - Beijing Natural Science Foundation; 2013M540859 - China Postdoctoral Science Foundation)Published versio