Direct Mannich reaction of glycinate Schiff bases with N-(8-quinolyl)sulfonyl imines: a catalytic asymmetric approach to anti-alpha,beta-diamino esters

Abstract

An efficient catalytic enantioselective direct Mannich reaction of glycinate Schiff bases with aryl imines leading to anticonfigured orthogonally protected alpha,beta-diaminoesters has been realized. Keys to success in this new catalyst system are the use of Fesulphos/Cu(CH3CN)4PF6 (3-5 mol%) as a Lewis acid catalyst and readily available N-(8-quinolyl)sulfonyl-protected aldimines as substrates, affording excellent levels of diastereo- (typically anti/syn > 90:10) and enantiocontrol (typically > or = 90% ee). A remarkable feature of this catalyst system is that it allows the construction of products with a tetrasubstituted carbon stereocenter at C-alpha in a highly diastereo- and enantiocontrolled manner.