A Chemoenzymatic Hydroaminomethylation Strategy for the Selective Synthesis of Linear Primary Amines from Olefins by Sequential and Tandem Processes

Abstract

Methods that form amines from feedstock chemicals are an important component of industrial chemistry. Many methods for the synthesis of amines yield mixtures of primary, secondary, and tertiary amines, necessitating costly downstream separations. We present a chemoenzymatic approach to hydroaminomethylation that addresses these challenges by combining hydroformylation catalyzed by a phosphine-bound rhodium complex with enzymatic transamination catalyzed by an ω-transaminase from Vibrio fluvialis (VfTA). This sequential chemoenzymatic hydroaminomethylation reaction converts olefins to linear primary amines with high regioselectivity and chemoselectivity for the linear primary amine, and we demonstrate that this process occurs with a series of olefins with varying structures. Furthermore, we report progress toward a tandem process that incorporates a biocatalytic cascade for recycling an intermediate amine donor, which is required for the transaminase enzyme to use an ammonium salt as the terminal nitrogen source. This study illustrates the potential to combine chemo- and biocatalytic reactions to produce valuable materials from readily available feedstocks in both tandem and sequential processes, with selectivities that have not been achieved with transition-metal catalysts.