Comprehensive Summary A visible light photocatalytic[3+2]cycloaddition of alkynes with readily accessible organic iodides as the C3 synthon is developed herein.By merging halogen atom transfer(XAT)and hydrogen atom tr...Comprehensive Summary A visible light photocatalytic[3+2]cycloaddition of alkynes with readily accessible organic iodides as the C3 synthon is developed herein.By merging halogen atom transfer(XAT)and hydrogen atom transfer(HAT),alkyl/aryl iodides serve as a formal diradical precursor and add across C-C triple bonds to deliver a number of functionalized cyclopentanes in moderate to high yields with exceptional regio-and diastereoselectivity.A reductive radical-polar crossover mechanism,involving the cascade XAT,radical addition,1,5-HAT,polar effect-promoted 5-endo annulation,single electron transfer(SET)reduction,and protonation,may account for this unprecedented dehalogenative[3+2]cycloaddition.This work not only expands the repertoire of the traditional RATC methodology,but also provides a robust platform for the expedient assembly of cyclopentanes,a valuable structural motif in the realms of medicinal chemistry and material sciences.展开更多
Compared to well-established 1,5-HAT of N-centered radicals,the synthetic applications of 1,2-HAT process were scarce due to the high barrier and constrained three-membered transition state.Here,we have developed a no...Compared to well-established 1,5-HAT of N-centered radicals,the synthetic applications of 1,2-HAT process were scarce due to the high barrier and constrained three-membered transition state.Here,we have developed a novel C(sp')-H gem-difluoroallylation via a base assisted formal 1,2-HAT of amidyl radicals with the reductive quenching cycle of photocatalyst.This transformation enables the efficient formation ofα-aminoalkyl radicals via 1,2-HAT and showcases good functional group tolerance.Our preliminary mechanistic experiments,along withDensity Functional Theory(DFT)calculations demonstrate thefeasibility of 1,2-HAT of amidyl radicals,especially when assisted by a base.Furthermore,our method also succeeds in the Giese addition of electron-deficient alkenes as well as styrene.展开更多
α-Fluoroalkyl (Rf) alcohols are privileged motifs in drugs and pharmaceutically active compounds.As such,it is highly desirable to develop efficient methods for assembling these scaffolds.Herein,a visible-light-induc...α-Fluoroalkyl (Rf) alcohols are privileged motifs in drugs and pharmaceutically active compounds.As such,it is highly desirable to develop efficient methods for assembling these scaffolds.Herein,a visible-light-induced cascade radical cyclization of alkenyl fluoroalkyl ketones is developed,producing a variety of decorate α-Rf cycloalkanols in promising yields with up to >20 : 1 dr selectivity.A radical chain mechanism involving an intramolecular radical addition to the α-Rf carbonyl group and a subsequent intermolecular hydrogen atom transfer (HAT) has been proposed.Density functional theory (DFT) calculations indicate that a fluorine effect contributes to the radical addition to carbonyls by lowering the π* (C=O) orbital energy of CORf and energy barrier of the HAT between alkoxy radicals and THF,which may be valuable for controllable transformations of fluorinated molecules.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(LZ20B020001 and LY23B020004)the Ten Thousand Talents Plan of Zhejiang Province(2020R52021)+1 种基金the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Province(2022R01007)the National Natural Science Foundation of China(22371262,22071218,and 22203076).
文摘Comprehensive Summary A visible light photocatalytic[3+2]cycloaddition of alkynes with readily accessible organic iodides as the C3 synthon is developed herein.By merging halogen atom transfer(XAT)and hydrogen atom transfer(HAT),alkyl/aryl iodides serve as a formal diradical precursor and add across C-C triple bonds to deliver a number of functionalized cyclopentanes in moderate to high yields with exceptional regio-and diastereoselectivity.A reductive radical-polar crossover mechanism,involving the cascade XAT,radical addition,1,5-HAT,polar effect-promoted 5-endo annulation,single electron transfer(SET)reduction,and protonation,may account for this unprecedented dehalogenative[3+2]cycloaddition.This work not only expands the repertoire of the traditional RATC methodology,but also provides a robust platform for the expedient assembly of cyclopentanes,a valuable structural motif in the realms of medicinal chemistry and material sciences.
基金We thank the National Natural Science Foundation of China(22001233)Zhejiang Provincial Ten Thousand Talent Program(2020R52021)and Zhejiang Normal University for financial support.
文摘Compared to well-established 1,5-HAT of N-centered radicals,the synthetic applications of 1,2-HAT process were scarce due to the high barrier and constrained three-membered transition state.Here,we have developed a novel C(sp')-H gem-difluoroallylation via a base assisted formal 1,2-HAT of amidyl radicals with the reductive quenching cycle of photocatalyst.This transformation enables the efficient formation ofα-aminoalkyl radicals via 1,2-HAT and showcases good functional group tolerance.Our preliminary mechanistic experiments,along withDensity Functional Theory(DFT)calculations demonstrate thefeasibility of 1,2-HAT of amidyl radicals,especially when assisted by a base.Furthermore,our method also succeeds in the Giese addition of electron-deficient alkenes as well as styrene.
基金The authors gratefully acknowledge the financial support from National Natural Science Foundation of China （Nos. 21625206, 21632009, 21572258, 21572259, 21421002, 21772098） and the Strategic Priority Research Program of the Chinese Academy of Sciences （No. XDB20000000） for financial support.
基金supported by the National Natural Science Foundation of China(22071218 and 22203076)the Natural Science Foundation of Zhejiang Province(LZ20B020001 and LY23B020004)+2 种基金the Ten Thousand Talents Plan of Zhejiang Province(2020R52021)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Province(2022R01007)Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province.
文摘α-Fluoroalkyl (Rf) alcohols are privileged motifs in drugs and pharmaceutically active compounds.As such,it is highly desirable to develop efficient methods for assembling these scaffolds.Herein,a visible-light-induced cascade radical cyclization of alkenyl fluoroalkyl ketones is developed,producing a variety of decorate α-Rf cycloalkanols in promising yields with up to >20 : 1 dr selectivity.A radical chain mechanism involving an intramolecular radical addition to the α-Rf carbonyl group and a subsequent intermolecular hydrogen atom transfer (HAT) has been proposed.Density functional theory (DFT) calculations indicate that a fluorine effect contributes to the radical addition to carbonyls by lowering the π* (C=O) orbital energy of CORf and energy barrier of the HAT between alkoxy radicals and THF,which may be valuable for controllable transformations of fluorinated molecules.
