Chemoenzymatic Synthesis of Enantiopure Amino Alcohols from Simple Methyl Ketones

Abstract

AbstractThis study highlights the straight‐forward synthesis of substituted 1,2‐amino alcohols from simple and readily available aromatic methyl ketones. Starting from acetophenone derivatives, the straight‐forward synthesis strategy involved an initial bromination of the alpha‐positioned methyl group in the first step, followed by a simple hydrolysis to the hydroxyketone (2‐hydroxyacetophenone). The hydroxylated intermediate was subsequently converted from Silicibacter pomeroyi to the final 1,2‐amino alcohol by using the transaminase. The transaminase‐catalyzed reaction proceeded with yields up to 62 % and always excellent enantiomeric excess of >99 %. Interestingly, the keto‐enol‐tautomerism of the hydroxyl ketone yields an unexpected amino alcohol isomer.