Water enabled, nickel-catalyzed highly chemoselective C-allylation of (NH)-indoles employing alcohols

Abstract

The first ‘in-water’ nickel-catalyzed chemoselective C₃-allylation of (NH)-indoles employing allylic alcohols under mild conditions is reported here. Different indoles and allylic alcohols were found compatible with excellent chemo- (C vs. N: >99%; C₂vs. C₃: >98%), regio- (linear vs. branch: >99%), and stereo-selectivity (E vs. Z: >99%) and functional group tolerance. The use of water not only provides sustainability by eliminating the need for organic solvent as reaction media but it also activates allylic alcohols via hydrogen bond networking and stabilizes the consequent hydroxide ion (strong solvation effect) resulting in facile oxidative addition, and thereof the formation of electrophilic π-allylNi complexes leading to C₃-allyl indoles. The study further highlights the first Hydrogen-bond assisted intermolecular N → C allylic migration via π-allylNi complexation and reports the first synthesis of allyl indoles using allylamine as electrophilic precursors.