Byun Seunghwan, Hwang Meemie U, Wise Henry R, Bay Anna V, Cheong Paul H-Y, Scheidt Karl A
Department of Chemistry, Northwestern University, Silverman Hall, Evanston, IL 60208, USA.
Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR 97331, USA.
Angew Chem Int Ed Engl. 2023 Dec 4;62(49):e202312829. doi: 10.1002/anie.202312829. Epub 2023 Nov 6.
An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp -carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.
公开了一种对映选择性卡宾催化的酰基咪唑与外消旋汉斯酯的自由基-自由基偶联反应。该方法涉及N-杂环卡宾衍生的羰游基与仲sp -碳自由基的偶联，能够以中等到良好的产率和对映选择性得到手性α-芳基脂肪族酮，且无任何竞争性差向异构化。各种药物化合物的后期官能团化突出了该方法的实用性，对映体富集产物向生物相关分子的转化进一步证明了这一点。计算研究表明，N-杂环卡宾分别控制羰游基和烷基的双面选择性。
