化学
硝基苯
芳基
对映选择合成
胺化
烷基
羟胺
炔丙基
炔烃
催化作用
组合化学
有机化学
作者
Zhen Liu,Zi-Yang Qin,Ledong Zhu,Soumitra V. Athavale,Arkajyoti Sengupta,Zhijun Jia,Marc Garcia‐Borràs,K. N. Houk,Frances H. Arnold
摘要
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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