乙基锌介导的乙烯基叠氮化物与碘二氟乙酸乙酯的自由基（3 + 2）环加成反应合成3,3-二氟-γ-内酰胺

EtZn-Mediated Radical (3 + 2) Cycloaddition of Vinyl Azides with Ethyl Iododifluoroacetate to Access 3,3-Difluoro-γ-lactams.

作者信息

Zhang Yifei, Jiang Bin, Liu Peijun, Liu Xiaozu

机构信息

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563000, China.

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, P. R. China.

出版信息

J Org Chem. 2023 Oct 20;88(20):14634-14639. doi: 10.1021/acs.joc.3c01620. Epub 2023 Oct 3.

DOI:10.1021/acs.joc.3c01620

PMID:37788008

Abstract

A diethylzinc-mediated radical (3 + 2) cycloaddition of vinyl azides with ethyl iododifluoroacetate is presented. The developed reaction features good functional group tolerance, broad substrate scope, and operational simplicity, enabling efficient assembly of a wide range of 3,3-difluoro-γ-lactam derivatives bearing an -substituted quaternary carbon center in moderate to good yields. The utility of the method is showcased by a scaled-up reaction, conversion of the product, and late-stage structural modifications of a variety of pharmaceutical compounds.

摘要

本文报道了二乙基锌介导的乙烯基叠氮化物与碘二氟乙酸乙酯的自由基（3 + 2）环加成反应。所开发的反应具有良好的官能团耐受性、广泛的底物范围和操作简便性，能够以中等到良好的产率高效组装一系列带有α-取代季碳中心的3,3-二氟-γ-内酰胺衍生物。该方法的实用性通过放大反应、产物转化以及多种药物化合物的后期结构修饰得以展现。