Amines are valuable commodity chemicals, serving as intermediates for industrial chemicals, such as surfactants and polymers, and they are important building blocks for fine chemicals, such as agrochemicals or pharmaceuticals. One common approach for the synthesis of alkyl amines is the reductive amination of carbonyl compounds often formed from hydroformylation. This transformation of olefins to amines through the addition of CO, H₂, and amine is known as hydroaminomethylation. Typical hydroaminomethylation methods require very high temperatures and pressures, which introduces selectivity issues, often requiring costly and inefficient downstream separation techniques to isolate the desired amine from the reaction mixture that includes secondary and tertiary amine side products.
We envisioned addressing this selectivity challenge by combining the well-studied hydroformylation reaction with enzymatic reductive amination to achieve the sole formation of primary amine products from long-chain alkene starting materials. We hypothesized that a biocatalytic system would overcome the challenges of overalkylation and poisoning by CO observed with transition metal catalysts. Our studies with wild-type and mutant transaminases (TA) from the organisms Vibrio fluvialis (Vf) and Chromobacterium violaceum (Cv) demonstrate the feasibility of this chemoenzymatic approach for a telescoped process and the potential to conduct a one-pot process wherein the hydroformylation and transamination occur under the same conditions. In a telescoped hydroformylation, reductive amination process with a rationally designed VfTA mutant, an overall yield of 74% was obtained of a linear, primary amine product from alkene starting material with no over alkylation products detected. The scope of this telescoped process is an active area of investigation, along with strategies to enhance the compatibility of the enzyme with the hydroformylation conditions.

Jenna Manske

University of California Berkeley

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