A Chemoenzymatic\nHydroaminomethylation Strategy for\nthe Selective Synthesis of Linear Primary Amines from Olefins by Sequential\nand Tandem Processes

Methods that form amines from feedstock chemicals are\nan important\ncomponent of industrial chemistry. Many methods for the synthesis\nof amines yield mixtures of primary, secondary, and tertiary amines,\nnecessitating costly downstream separations. We present a chemoenzymatic\napproach to hydroaminomethylation that addresses these challenges\nby combining hydroformylation catalyzed by a phosphine-bound rhodium\ncomplex with enzymatic transamination catalyzed by an ω-transaminase\nfrom Vibrio fluvialis (<i>Vf</i>TA). This sequential chemoenzymatic hydroaminomethylation reaction\nconverts olefins to linear primary amines with high regioselectivity\nand chemoselectivity for the linear primary amine, and we demonstrate\nthat this process occurs with a series of olefins with varying structures.\nFurthermore, we report progress toward a tandem process that incorporates\na biocatalytic cascade for recycling an intermediate amine donor,\nwhich is required for the transaminase enzyme to use an ammonium salt\nas the terminal nitrogen source. This study illustrates the potential\nto combine chemo- and biocatalytic reactions to produce valuable materials\nfrom readily available feedstocks in both tandem and sequential processes,\nwith selectivities that have not been achieved with transition-metal\ncatalysts.