Catalytic asymmetric formal (2 + 3) cycloaddition involving methyl-substituted 2-indolylmethanols†

Abstract

A catalytic asymmetric formal (2 + 3) cycloaddition of methyl-substituted 2-indolylmethanols with 3-substituted-2-indolylmethanols was conducted in the presence of chiral phosphoric acids, which delivered a series of chiral pyrrolo[1,2-α]indoles in overall high yields (up to 98%) with excellent diastereoselectivities (all >95 : 5 dr) and good enantioselectivities (up to 94% ee). Moreover, theoretical calculations provided an in-depth understanding of the reaction pathways. This work not only establishes the first catalytic asymmetric cycloaddition of methyl-substituted 2-indolylmethanols, but also realizes the first catalytic asymmetric formal (2 + 3) cycloaddition between different 2-indolylmethanols, which will enrich the chemistry of indolylmethanols.