Organocatalytic Asymmetric Annulation of ortho-Alkynylanilines: Synthesis of Axially Chiral Naphthyl-C2-indoles

Angew Chem Int Ed Engl. 2019 Nov 25;58(48):17199-17204. doi: 10.1002/anie.201908961. Epub 2019 Oct 15.

Abstract

A chiral Brønsted base catalyzed asymmetric annulation of ortho-alkynylanilines has been developed to access axially chiral naphthyl-C2-indoles via vinylidene ortho-quinone methide (VQM) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl-C2-indole skeletons with excellent enantioselectivity and functional-group tolerance. This transformation was applicable to decagram-scale preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction was demonstrated by a variety of transformations towards chiral naphthyl-C2-indoles for a series of carbon-heteroatom bond formations. Furthermore, the prepared axially chiral naphthyl-C2-indoles were applied as a chiral skeleton for organocatalytic aza-Baylis-Hillman reaction and asymmetric formal [4+2] tandem cyclization to give the corresponding adducts in high yields with improved enantioselectivity and diastereoselectivity.

Keywords: asymmetric catalysis; atroposelectivity; axially chirality; indoles; organocatalysis.