Diastereoselective Aldehyde-Amine-Alkyne Coupling Reaction: Synthesis of Biologically Active Molecules

Abstract

The chiral vicinal amino-alcohols and diamines moieties are found in a variety of biologically important compounds, e.g. natural products, naturally occurring peptides, pharmacologically active compounds as well as in transition-metal-based catalysts and organocatalysts for asymmetric synthesis. We sought to investigate new routes for chiral vicinal amino-alcohols and diamines using Cu(I) catalyzed diastereoselective three-component coupling reaction of aldehyde, amine and alkyne. We have demonstrated the diastereoselective formation of syn-α-amino alcohol derivative and its application in the synthesis of (+)-β-conhydrine and its piperidine as well as pyrrolidine analogues. We have also established the versatility of the methodology through the synthesis (2S,3R)-α-hydroxy-β-amino acid ((2S,3R)-AHBAs) derivatives, dipeptide natural product valinoctin A, and formal synthesis of both enantiomers of vigabatrin. Further, we have established diastereoselective routes to synthesis of syn-α,β-diamine derivative and its utility for the stereoselective synthesis of the quinolizidine alkaloid (+)-epiquinamide and its novel indolizidine analogue.