Synergistic Diastereo- and Enantioselective Functionalization of Unactivated Alkyl Quinolines with α,β-Unsaturated Aldehydes

Abstract

A novel alkyl functionalization of unactivated alkyl quinolines has been developed combining InCl₃ activation with organocatalytic activation of α,β-unsaturated aldehydes in a synergistic fashion. The reaction proceeds in a highly stereoselective manner as a sequence involving two consecutive synergistic catalytic cycles (Lewis acid- and iminium ion-catalyzed) and requires neither pre-activated alkyl quinoline substrates with electron-withdrawing substituents nor highly activated electrophiles. The reaction provides selectively double- or mono-addition products in good yields and high to excellent stereoselectivities. Furthermore, based on spectroscopic and labelling experiments, the mechanisms for the reactions are discussed.

Keywords: asymmetric catalysis; heterocycles; indium; organocatalysis; synergistic catalysis.