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Updated: Oct 9, 2025

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Published on: August 16, 2018
An Enzymatic Platform for Primary Amination of 1-Aryl-2-alkyl Alkynes
Zhen Liu1, Zi-Yang Qin1, Ledong Zhu2
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Abstract:
Propargyl amines are versatile synthetic intermediates with numerous applications in the pharmaceutical industry. An attractive strategy for efficient preparation of these compounds is nitrene propargylic C(sp3)-H insertion. However, achieving this reaction with good chemo-, regio-, and enantioselective control has proven to be challenging. Here, we report an enzymatic platform for the enantioselective propargylic amination of alkynes using a hydroxylamine derivative as the nitrene precursor. Cytochrome P450 variant PA-G8 catalyzing this transformation was identified after eight rounds of directed evolution. A variety of 1-aryl-2-alkyl alkynes are accepted by PA-G8, including those bearing heteroaromatic rings. This biocatalytic process is efficient and selective (up to 2610 total turnover number (TTN) and 96% ee) and can be performed on preparative scale.
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