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Updated: Jun 26, 2025

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Practical Synthesis of Chiral α-Aminophosphonates with Weak Bonding Organocatalysis at ppm Loading
Jiaxiang Lu1, Yang Yu1, Zhenghua Li1
1Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou 310030, China.
Abstract:
α-Aminophosphonic acids as an important class of bioisosteres of α-amino acids demonstrate various biologically important activities. We report here the development of a highly enantioselective isomerization of α-iminophosphonates enabled by an extraordinarily efficient organocatalyst. This organocatalyst afforded a total turnover number (TON) of 20,000-1,000,000 for a wide range of α-alkyl iminophosphonates. Even at a parts-per-million (ppm) loading, this catalyst achieved a complete reaction in greater than 93% enantiomeric excess (ee). Computational studies revealed that this small-molecule catalyst achieved enzyme-like efficiency via a network of weak bonding interactions that effectively preorganized the substrate and catalyst toward a transition-state-like complex. Considering the substrate tolerance, catalytic efficiency, and mechanism, this organocatalyst could be regarded as a small-molecule isomerase.
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