Homologation of aryl ketones to long-chain ketones and aldehydes via C–C bond cleavage
Xing Wang,
Ling-Jun Li,
Zhen-Yu Wang,
Hui Xu,
Hui-Xiong Dai
Affiliations
Xing Wang
CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Ling-Jun Li
CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Zhen-Yu Wang
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
Hui Xu
CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Corresponding author
Hui-Xiong Dai
CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China; Corresponding author
Summary: Transition metal-catalyzed C–C bond cleavage is a powerful tool for the reconstruction of a molecular skeleton. We report herein the multi-carbon homologation of aryl ketones to long-chain ketones and aldehydes via ligand-promoted Ar−C(O) bond cleavage and subsequent cross coupling with alkenols. Various (hetero)aryl ketones are compatible in the reaction, affording the corresponding products wtih good to excellent yields with high regioselectivity. Further applications in the late-stage diversification of biologically important molecules demonstrate the synthetic utility of this protocol. Mechanistic studies indicate that the ligand plays an important role in both C–C bond cleavage and the asymmetric migration-insertion process.
