Optimized stereoselective and scalable synthesis of five‐membered cyclic trans‐β‐amino acid building blocks via reductive amination

Abstract

We present an optimized method for the stereoselective synthesis of five‐membered alicyclic and heterocyclic trans‐β‐amino acid derivatives. The process involves a reductive amination of β‐keto esters using chiral auxiliary amines, with formic acid acting as a facilitator for rapid, diastereoselective reductions under gentle conditions. Our approach notably enhances isolated yields and permits the scalable production of trans‐2‐aminocyclopentanecarboxylic acid (trans‐ACPC), 4‐aminopyrrolidine‐3‐carboxylic acid (trans‐APC), 4‐aminotetrahydrofuran‐3‐carboxylic acid (trans‐ATFC), and 4‐aminotetrahydrothiophene‐3‐carboxylic acid (trans‐ATTC) building blocks.