Diastereo- and Enantioselective Synthesis of 9-Aryl-1-vinyl-tetrahydro-β-carbolines via Brønsted Acid-Catalyzed Pictet-Spengler Reaction.

Abstract

Reported herein is a stereoselective synthesis of 9-aryl-1-vinyl-tetrahydro-β-carbolines via a Pictet-Spengler reaction. This reaction proceeds via Brønsted acid-catalyzed cyclization of N-indole-tethered allenamides with >20:1 dr under mild conditions, while chiral phosphoric acid catalysis installs the C-N axial chirality with high enantioselectivity (up to 98% ee). An ortho-amide directing group and proper choice of catalyst prove crucial for the stereocontrol. Furthermore, divergent derivatizations of the products, particularly elaboration of the vinyl group, highlight the synthetic utility of this protocol.