A Carbene Relay Strategy for Cascade Insertion Reactions

作     者：Li Li Chenggang Mi Guanwang Huang Meirong Huang Yuyi Zhu Shao-Fei Ni Zhaofeng Wang Yong Huang 

作者机构：Department of Chemistry The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong SAR China State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha Hunan 410082 China Shenzhen Bay Laboratory Shenzhen 518132 China Laboratory of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen 518055 China Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province Shantou University Shantou Guangdong 515063 China 

出 版 物：《Angewandte Chemie》 (应用化学)

年 卷 期：2023年第135卷第45期

页      面：e202312793-e202312793页

学科分类：081704[工学-应用化学] 08[工学] 0817[工学-化学工程与技术] 

主　　题：Carbene Relay Fischer Carbene Heteroatom-Substituted Carbene Insertion Reaction Ketal Synthesis 

摘      要：Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α-heteroatoms to carbonyl compounds. Nevertheless, the limited availability of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I (III) /S (VI) reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α-heteroatom-substituted metal carbenes in one reaction. We found that this mixed I (III) /S (VI) ylide reacts efficiently with a transition metal catalyst and an X−H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium- and an X-substituted Rh-carbenes, enabling further reactions with another Y−H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α- O , O -, α,α- O , N -, and α,α- N , N -subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C−H/C−S double insertion, and C−S/Y−H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α-carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α-heteroatoms using a common precursor.