首页|Stereodivergent synthesis of α-fluoro α-azaaryl γ-butyrolactones via cooperative copper and iridium catalysis

Stereodivergent synthesis of α-fluoro α-azaaryl γ-butyrolactones via cooperative copper and iridium catalysis

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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.

Asymmetric catalysisα-Fluoro γ-butyrolactonesSynergistic catalysisCascade reactionStereodivergent synthesis

Kui Tian、Xin Chang、Lu Xiao、Xiu-Qin Dong、Chun-Jiang Wang

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College of Chemistry and Molecular Sciences,Engineering Research Center of Organosilicon Compounds & Materials,Ministry of Education,Wuhan University,Wuhan 430072,China

State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Shanghai 230021,China

Suzhou Institute of Wuhan University,Suzhou 215123,China

国家重点研发计划国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金湖北省自然科学基金湖北省自然科学基金江苏省自然科学基金中国博士后科学基金National Youth Talent Support Program,and Fundamental Research Funds for the Central Universities

2023YFA150670022071186220711872210121622271226223712162020CFA0362021CFA069BK201902132021M7025142042022kf1180

2024

10.1016/j.fmre.2022.07.008

自然科学基础研究(英文)

自然科学基础研究(英文)

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年,卷(期)：2024.(1)
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