Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones:Access to Chiral 2-Substituted Cyclopentyl Aryl Ketones  

作　　者：Zhengdong Ding Feng Gao Yining Lu Qianjia Yuan Wei-Ping Deng Wanbin Zhang 

机构地区：[1]Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,Frontiers Science Center for Transformative Molecules,School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China [2]Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China [3]Key Laboratory of the Ministry of Education for Advanced Catalysis Materials,Department of Chemistry,Zhejiang Normal University,Jinhua 321004,China

出　　处：《Precision Chemistry》2023年第3期146-152,共7页精准化学（英文）

基　　金：supported by the National Key R&D Program of China(No.2018YFE0126800);the National Natural Science Foundation of China(Nos.21991112 and 22001164);the Shanghai Pujiang Program(20PJ1406400).

摘　　要：Asymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic.Herein,we report an efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones for the synthesis of chiral 2-substituted cyclopentyl aryl ketones,an important chiral structural motif for the preparation of chiral pharmaceuticals and bioactive molecules.The reaction proceeded very well with good functional group compatibility and delivered the hydrogenated products in high yields and stereoselectivities(up to 99% yield,>20:1 dr and 99%ee).In addition,the reaction could be carried out on a gram-scale,and all four stereoisomers of the hydrogenated products bearing two contiguous stereocenters were obtained.Furthermore,the hydrogenated product can be transformed into the ERβ agonist Erteberel,and the reaction pathway was also studied via deuterium-labelling experiments.

关 键 词：asymmetric hydrogenation tetrasubstituted alkenes IRIDIUM chiral cyclopentane 2-substituted cyclopentyl aryl ketones 

分 类 号：O621.251[理学—有机化学]