Stereodivergent synthesis ofα-fluoroα-azaarylγ-butyrolactones via cooperative copper and iridium catalysis  

作　　者：Kui Tian Xin Chang Lu Xiao Xiu-Qin Dong Chun-Jiang Wang 

机构地区：[1]College of Chemistry and Molecular Sciences,Engineering Research Center of Organosilicon Compounds&Materials,Ministry of Education,Wuhan University,Wuhan 430072,China [2]State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Shanghai 230021,China [3]Suzhou Institute of Wuhan University,Suzhou 215123,China

出　　处：《Fundamental Research》2024年第1期77-85,共9页自然科学基础研究（英文版）

基　　金：We are grateful for financial support from the National Key R&D Program of China(2023YFA1506700);National Natural Science Foundation of China(22071186,22071187,22101216,22271226,and 22371216);Natural Science Foundation of Hubei Province(2020CFA036,2021CFA069);Natural Science Foundation of Jiangsu Province(BK20190213);China Postdoctoral Science Foundation(2021M702514);National Youth Talent Support Program,and Fundamental Research Funds for the Central Universities(2042022kf1180).

摘　　要：The development of stereodivergent synthetic methods to access all four stereoisomers of biologically importantα-fluoroγ-butyrolactones containing vicinal stereocenters is of great importance and poses a formidable challenge owing to ring strain and steric hindrance.Herein,a novel asymmetric[3+2]annulation ofα-fluoroα-azaaryl acetates with vinylethylene carbonate was successfully developed through Cu/Ir-catalyzed cascade allylic alkylation/lactonization,affording a variety of enantioenrichedα-fluoroγ-butyrolactones bearing vicinal stereogenic centers with high reaction efficiency and excellent levels of both stereoselectivity and regioselectivity(up to 98%yield,generally>20:1 dr and>99%ee).Notably,all four stereoisomers of these pharmaceutically valuable molecules could be accessed individually via simple permutations of two enantiomeric catalysts.In addition,other azaaryl acetates bearingα-methyl,α-chlorine orα-phenyl group were tolerated well in this transformation.Reaction mechanistic investigations were conducted to explore the process of this bimetallic catalysis based on the results of reaction intermediates,isotopic labelling experiments,and kinetic studies.

关 键 词：Asymmetric catalysis α-Fluoroγ-butyrolactones Synergistic catalysis Cascade reaction Stereodivergent synthesis 

分 类 号：O62[理学—有机化学]