Because of the widespread applications of optically active alkyl fluorides in medicinal and agro chem-icals,enantioselective and even stereodivergent construction of alkyl fluorides remains highly desirable but underd...Because of the widespread applications of optically active alkyl fluorides in medicinal and agro chem-icals,enantioselective and even stereodivergent construction of alkyl fluorides remains highly desirable but underdeveloped.Transition-metal-catalyzed asymmetric hydrofluoroalkylation of readily available di-enes represents a novel route to achieve this goal,yet receives scarce study.Here we report an intrigu-ing palladium-catalyzed enantioselective hydromonofluoroalkylation reaction of conjugated dienes.Both monosubstituted and internal dienes proceed well with the transformation and furnish alkyl fluorides in generally>80%yield and>90%ee.A stereodivergent hydromonofluoroalkylation protocol via Pd/Cu co-catalysis is also established for the access to all four stereoisomers of corresponding moieties bear-ing a fully-substituted F-stereogenic center and vicinal tertiary carbon center.In addition,asymmetric migratory hydromonofluoroalkylation of skipped dienes is developed to realize the direct allylic C-H flu-oroalkylation.A compound library of enantioenriched cyclic fluorides is thus built to highlight the trans-formation potential of present methodology.展开更多
Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process,herein,the authors present a novel strategy to allow trans-exo-selective aryla...Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process,herein,the authors present a novel strategy to allow trans-exo-selective arylative cyclization of 1,6-enynes.Through initiation of rhodium(III)-catalyzed C-H activation,a diverse range of N-heterocyclic directing groups,including pyridine,pyrazole,imidazo[1,2-a]pyridine,benzoxazole,benzothiazole,and purine,was feasible for the cascade transformation,exhibiting high efficiency(up to 92%yield),broad substrate scope,and excellent functional group compatibility.Moreover,the modification of natural products and pharmaceutical compounds was also demonstrated to showcase its synthetic utility.Based on density functional theory(DFT)calculations,a key three-membered ring intermediate through the insertion relay,rather than the direct E/Z isomerization of alkenyl rhodium species,controlled the stereochemical outcome for this trans-exo-selective cyclization.The subsequent ring-opening protonation of the more favored rotamer led to exclusive trans-exo-selectivity.展开更多
基金the National Natural Science Foundation of China(NSFC,No.22071262)Science and Technology Commission of Shanghai Municipality(No.22ZR1475200)+1 种基金Shanghai Rising-Star program(No.20QA1411300)CAS Key Laboratory of Synthetic Chemistry of Natural Substances,and Shanghai Institute of Organic Chemistry for financial support.
文摘Because of the widespread applications of optically active alkyl fluorides in medicinal and agro chem-icals,enantioselective and even stereodivergent construction of alkyl fluorides remains highly desirable but underdeveloped.Transition-metal-catalyzed asymmetric hydrofluoroalkylation of readily available di-enes represents a novel route to achieve this goal,yet receives scarce study.Here we report an intrigu-ing palladium-catalyzed enantioselective hydromonofluoroalkylation reaction of conjugated dienes.Both monosubstituted and internal dienes proceed well with the transformation and furnish alkyl fluorides in generally>80%yield and>90%ee.A stereodivergent hydromonofluoroalkylation protocol via Pd/Cu co-catalysis is also established for the access to all four stereoisomers of corresponding moieties bear-ing a fully-substituted F-stereogenic center and vicinal tertiary carbon center.In addition,asymmetric migratory hydromonofluoroalkylation of skipped dienes is developed to realize the direct allylic C-H flu-oroalkylation.A compound library of enantioenriched cyclic fluorides is thus built to highlight the trans-formation potential of present methodology.
基金Financial support was generously provided by the National Natural Science Foundation of China(nos.21871184,21871284,21702182,and 21873081),the Shanghai Municipal Education Commission(no.2019-01-07-00-10-E00072),the Science and Technology Commission of Shanghai Municipality(no.18401933500),the Strategic Priority Research Program of the Chinese Academy of Sciences(no.XDB 20020100),the Key Research Program of Frontier Science(no.QYZDYSSW-SLH026),the Fundamental Research Funds for the Central Universities(no.2019QNA3009),and the China Postdoctoral Science Foundation(no.2018M640546).Calculations were performed on the high-performance computing system at the Department of Chemistry,Zhejiang University.The authors thank Jie Sun(Shanghai Institute of Organic Chemistry)for X-ray crystallographic analysis.
文摘Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process,herein,the authors present a novel strategy to allow trans-exo-selective arylative cyclization of 1,6-enynes.Through initiation of rhodium(III)-catalyzed C-H activation,a diverse range of N-heterocyclic directing groups,including pyridine,pyrazole,imidazo[1,2-a]pyridine,benzoxazole,benzothiazole,and purine,was feasible for the cascade transformation,exhibiting high efficiency(up to 92%yield),broad substrate scope,and excellent functional group compatibility.Moreover,the modification of natural products and pharmaceutical compounds was also demonstrated to showcase its synthetic utility.Based on density functional theory(DFT)calculations,a key three-membered ring intermediate through the insertion relay,rather than the direct E/Z isomerization of alkenyl rhodium species,controlled the stereochemical outcome for this trans-exo-selective cyclization.The subsequent ring-opening protonation of the more favored rotamer led to exclusive trans-exo-selectivity.
