CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides & Chemical Biology Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei, 430079, China.
College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, 310036, China.
Angew Chem Int Ed Engl. 2021 Oct 11;60(42):22956-22962. doi: 10.1002/anie.202110084. Epub 2021 Sep 9.
Kharasch-Sosnovsky reaction is one of the most powerful methods for allylic oxidation of alkenes. However, the inherent radical mechanism and use of peroxides as both oxidants and oxygen nucleophiles render dearth of universal catalytic systems for highly enantioselective variants and limited scope. Herein, an alternative to the asymmetric Kharasch-Sosnovsky reaction that utilized a chiral copper catalyst and purple-LED irradiation to enable the three-component coupling of 1,3-dienes, oxime esters, and carboxylic acids is reported. This protocol features mild conditions, remarkable scope and functional group tolerance as evidenced by >80 examples and utility in the late-stage modification of pharmaceuticals and natural products. Detailed mechanistic studies provide evidences for the radical-based reaction pathway.
Kharasch-Sosnovsky 反应是烯丙基氧化反应中最强大的方法之一。然而，由于其固有的自由基机制以及使用过氧化物作为氧化剂和氧亲核试剂，使得高度对映选择性变体和有限范围的通用催化体系缺乏。在此，报告了一种替代的不对称 Kharasch-Sosnovsky 反应，该反应使用手性铜催化剂和紫外 LED 照射，实现了 1,3-二烯、肟酯和羧酸的三组分偶联。该方案具有温和的条件、显著的范围和官能团耐受性，通过 80 多个实例和在药物和天然产物的后期修饰中的应用得到了证明。详细的机理研究为基于自由基的反应途径提供了证据。
