Enantioselective total syntheses of (−)-mitragynine, (−)-quinine and (+)-quinidine enabled by Ir-catalysed asymmetric hydrogenation of all-carbon tetrasubstituted cycloalkenes

Abstract

Enantioselective total syntheses of three alkaloids (−)-mitragynine, (−)-quinine and (+)-quinidine are reported. These syntheses rely on an Ir-catalysed asymmetric hydrogenation of tetrasubstituted α-acylpyrazole-β-alkyl cycloalkenes to construct piperidine rings bearing 1,2-contiguous cis-stereocenters in high yields (90% and 97%) with excellent enantioselectivities (93% and 96% ee).