Abstract
The development of stereodivergent synthetic methods to access all four stereoisomers of biologically impor-tant α-fluoro γ-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 of α-fluoro α-azaaryl acetates with vinylethylene carbonate was successfully developed through Cu/Ir-catalyzed cascade allylic alkylation/lactonization,affording a variety of enantioenriched α-fluoro γ-butyrolactones bearing vicinal stere-ogenic 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 valu-able molecules could be accessed individually via simple permutations of two enantiomeric catalysts.In addition,other azaaryl acetates bearing α-methyl,α-chlorine or α-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.
基金项目
国家重点研发计划(2023YFA1506700)
国家自然科学基金(22071186)
国家自然科学基金(22071187)
国家自然科学基金(22101216)
国家自然科学基金(22271226)
国家自然科学基金(22371216)
湖北省自然科学基金(2020CFA036)
湖北省自然科学基金(2021CFA069)
江苏省自然科学基金(BK20190213)
中国博士后科学基金(2021M702514)
National Youth Talent Support Program,and Fundamental Research Funds for the Central Universities(2042022kf1180)
NETL
NSTL
万方数据