Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids.

Abstract

Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products and pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis of tetrahydro-β-carboline skeletons have immense impacts and have attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition of 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types of chiral tetrahydro-β-carbolines bearing continuous multi-chiral centers and quaternary chiral centers. The method displays different endo/exo selectivity from traditional nitrone chemistry. The distinct power of this strategy has been illustrated by application to collective and enantiodivergent total syntheses of 40 tetrahydro-β-carboline-type indole alkaloid natural products with divergent stereochemistry and varied architectures.