Palladium-Catalyzed Enantioselective Intermolecular Hydroamination of 1,3-Dienes with Alkyl Amines

Abstract

Chiral amines are a common motif among many important natural products and biologically active molecules. For this reason, methods to synthesize chiral amines have long been sought by organic chemists. Hydroamination is an appealing route to access chiral amines due to the atom economy of the transformation and simplicity of the starting materials. Despite the allure of such reactions, few methods exist for intermolecular hydroaminations, let alone enantioselective versions. Herein, we report the first enantioselective intermolecular hydroamination of 1,3-dienes with alkyl amines. Transformations with a Pd–phosphinooxazoline catalyst are efficient (up to 96% yield) and enantioselective (up to 96.5:3.5 e.r.) for a broad range of substituted dienes and amines. Diene geometry and electronics as well as isotope effects significantly affect product distribution. Preliminary investigations indicate that enantioselectivity diminishes over time with secondary acyclic amines. All chiral products are formed as allylic amines with an alkene poised for downstream functionalization.