Enantioselective dearomative prenylation of indole derivatives

Abstract

Prenylation is a ubiquitous process common to almost all living organisms, and a key transformation in organic synthesis. Dearomative prenylation reactions of tryptophan derivatives lead to various prenylated indoline alkaloids with diverse biological activities. However, enantioselective dearomative prenylations without a pre-installed stereogenic centre in the substrate have not been reported. Here, we show that a small molecule-based catalytic system derived from a commercially available palladium precursor and a chiral phosphoramidite ligand (allylphos) can catalyse the enantioselective dearomative prenylation of indole derivatives, which tolerates a much broader substrate scope than those of known enzymatic dearomative prenylation processes. Enantioselective dearomative geranylation and farnesylation reactions also proceed smoothly under the standard conditions. The concise total or formal syntheses of a series of natural products can be realized using this catalytic system. The mechanistic investigations provide deep insights for the further design of chiral ligands and catalysts for asymmetric reactions. Prenylation is a common step in the synthesis of many natural products, and enantioselective variants require the use of enzymatic catalysts. Now, You and co-workers report a palladium phosphoramidite catalyst capable of enantioselective, dearomative prenylations across a broad range of starting materials, and demonstrate its power in a number of natural product syntheses.