Herein,we report a switchable divergent strainrelease/rearrangement cascade of bicyclo[1.1.0]butanes(BCBs),enabled by monoatomic oxygen or nitrogen insertion.Four distinct molecular scaffolds are accessed via the cond...Herein,we report a switchable divergent strainrelease/rearrangement cascade of bicyclo[1.1.0]butanes(BCBs),enabled by monoatomic oxygen or nitrogen insertion.Four distinct molecular scaffolds are accessed via the condition-dependent cascades:oxygen insertion affordsβ-methylene carbonyls via oxa-bicyclo[1.1.1]pentane-mediated ring opening and decarbonylation,itaconate derivatives via Grob-type ring opening,and cis-cyclopropanes via ring contraction;nitrogen insertion,in contrast,triggers ring expansion to form 2,4-disubstituted pyrroles.This strategy rapidly delivers bioactive-like frameworks with broad functional group tolerance.Synthetic utility is demonstrated by modular synthesis of bioactive molecules such as Esonarimod,Ralfuranone,and Rubrolide E.Mechanistic studies reveal that the position of the leaving group,whether on the heteroatom itself,theβ-carbon,or theγ-carbon,within heteroatom-substituted cyclobutane intermediates dictates the divergent outcomes.These results establish a conceptually novel heteroatommediated strategy for programmable strain-release/rearrangement cascades,significantly expanding the reactivity profile of BCBs.展开更多
Herein,we report the synthesis of multifunctionalized trans-and cis-cyclobutane-basedγ-aminobutyric acid derivatives via diastereodivergent Cu(OTf)_(2)-catalyzed strain-release reactions of bicyclo[1.1.0]butanes with...Herein,we report the synthesis of multifunctionalized trans-and cis-cyclobutane-basedγ-aminobutyric acid derivatives via diastereodivergent Cu(OTf)_(2)-catalyzed strain-release reactions of bicyclo[1.1.0]butanes with amines.This protocol enables precise control of product configuration via ligand selection,providing a powerful tool for modulating the stereochemistry of the resulting compounds.In addition,the synthesized cyclobutane-basedγ-aminobutyric acid derivatives significantly expand substituent diversity,thereby greatly enhancing molecular complexity.The method proceeds under mild conditions and exhibits excellent tolerance toward a broad range of functional groups,making it a versatile platform for the development of novel drug candidates.展开更多
Strain-release ring-opening trifluoromethylthiolation to construct SCF3-substituted cyclic motifs was under-explored,and di-trifluoromethylthiolation is unachieved.Herein,we present the first trifluoromethylthiolation...Strain-release ring-opening trifluoromethylthiolation to construct SCF3-substituted cyclic motifs was under-explored,and di-trifluoromethylthiolation is unachieved.Herein,we present the first trifluoromethylthiolation of bicyclo[1.1.0]butane(BCB)and bicyclo[2.1.0]pentane.By employing different activators,both mono-and di-trifluoromethylthio substituted cyclobutane and cyclopentane derivatives were successfully obtained.展开更多
The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobut...The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobutyl amides with C(sp^(3))−H feedstocks is achieved in an atom-economic and photocatalyst-and light-free manner.This protocol follows a sequential C(sp^(3))–H/C(sp^(2))–H functionalization,providing an efficient route for diversity-oriented synthesis of functionalized 3-spirocyclobutyl oxindoles.In particular,a wide range of C(sp^(3))−H feedstocks,including ether,alcohol,amine,thioether,polychlorinated methane,silane,acetone,acetonitrile,toluene,and alkane are all suitable for the C(sp^(3))−H functionalization,demonstrating the broad applicability of this transformation.展开更多
Cyclobutane derivatives have been recognized as useful structural motifs in organic synthesis and drug design.With the revival of photochemistry,the enantioselective synthesis of cyclobutane derivatives using[2+2]-cyc...Cyclobutane derivatives have been recognized as useful structural motifs in organic synthesis and drug design.With the revival of photochemistry,the enantioselective synthesis of cyclobutane derivatives using[2+2]-cycloadditions has garnered numerous attentions.On the other hand,enantioselec-tive functionalization of preformed four-membered carbocycles is emerging as an important complementary approach to access chiral cyclobutane de-rivatives with versatile structural patterns.Herein,we summarize recent advances in this field from 2012.To avoid undesired C—C bond cleavage driv-en by strain-releasing,it is crucial to choose compatible methods for enantioselective functionalization and meanwhile preserving intact four-membered ring skeleton.Guided by calculated hydrogenation enthalpies,which are used to evaluate the strain energy of indicated C—C bond,a clear picture of the developed methodologies on functionalization of four-membered carbocycles combining the strain energy and enhanced reactivity is presented.展开更多
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(grant no.2022R01007)National Key Research and Development Program of China(grant no.2021YFA0804900)the Start-up Research Grant from Zhejiang Normal University.
文摘Herein,we report a switchable divergent strainrelease/rearrangement cascade of bicyclo[1.1.0]butanes(BCBs),enabled by monoatomic oxygen or nitrogen insertion.Four distinct molecular scaffolds are accessed via the condition-dependent cascades:oxygen insertion affordsβ-methylene carbonyls via oxa-bicyclo[1.1.1]pentane-mediated ring opening and decarbonylation,itaconate derivatives via Grob-type ring opening,and cis-cyclopropanes via ring contraction;nitrogen insertion,in contrast,triggers ring expansion to form 2,4-disubstituted pyrroles.This strategy rapidly delivers bioactive-like frameworks with broad functional group tolerance.Synthetic utility is demonstrated by modular synthesis of bioactive molecules such as Esonarimod,Ralfuranone,and Rubrolide E.Mechanistic studies reveal that the position of the leaving group,whether on the heteroatom itself,theβ-carbon,or theγ-carbon,within heteroatom-substituted cyclobutane intermediates dictates the divergent outcomes.These results establish a conceptually novel heteroatommediated strategy for programmable strain-release/rearrangement cascades,significantly expanding the reactivity profile of BCBs.
基金financial support from the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(2022R01007)the Start-up Research Grant from Zhejiang Normal University.
文摘Herein,we report the synthesis of multifunctionalized trans-and cis-cyclobutane-basedγ-aminobutyric acid derivatives via diastereodivergent Cu(OTf)_(2)-catalyzed strain-release reactions of bicyclo[1.1.0]butanes with amines.This protocol enables precise control of product configuration via ligand selection,providing a powerful tool for modulating the stereochemistry of the resulting compounds.In addition,the synthesized cyclobutane-basedγ-aminobutyric acid derivatives significantly expand substituent diversity,thereby greatly enhancing molecular complexity.The method proceeds under mild conditions and exhibits excellent tolerance toward a broad range of functional groups,making it a versatile platform for the development of novel drug candidates.
基金supported by the National Key Research and Development Program of China(2021YFF0701700)the NFSC(21925105 and 92156001)+1 种基金the Natural Science Foundation of Tianjin(grant no.24JCZDJC00700)the Haihe Laboratory of Sustainable Chemical Transformations,and the Fundamental Research Funds for the Central Universities.
文摘Strain-release ring-opening trifluoromethylthiolation to construct SCF3-substituted cyclic motifs was under-explored,and di-trifluoromethylthiolation is unachieved.Herein,we present the first trifluoromethylthiolation of bicyclo[1.1.0]butane(BCB)and bicyclo[2.1.0]pentane.By employing different activators,both mono-and di-trifluoromethylthio substituted cyclobutane and cyclopentane derivatives were successfully obtained.
基金funded by National Natural Science Foundation of China(No.22201070).
文摘The difunctionalization of bicyclo[1.1.0]butanes is an under-explored transformation that accesses to moieties that are otherwise difficult to prepare.Herein,a new oxidative radical alkylarylation of N-aryl bicyclobutyl amides with C(sp^(3))−H feedstocks is achieved in an atom-economic and photocatalyst-and light-free manner.This protocol follows a sequential C(sp^(3))–H/C(sp^(2))–H functionalization,providing an efficient route for diversity-oriented synthesis of functionalized 3-spirocyclobutyl oxindoles.In particular,a wide range of C(sp^(3))−H feedstocks,including ether,alcohol,amine,thioether,polychlorinated methane,silane,acetone,acetonitrile,toluene,and alkane are all suitable for the C(sp^(3))−H functionalization,demonstrating the broad applicability of this transformation.
基金We are grateful for the financial support from the National Natural Science Foundation of China(22071028,21772024,21921003 to P.L.21801044,22071122 to H.F.)We thank Dr.Huize Jing for her work on illustrations of rope acrobatics.
文摘Cyclobutane derivatives have been recognized as useful structural motifs in organic synthesis and drug design.With the revival of photochemistry,the enantioselective synthesis of cyclobutane derivatives using[2+2]-cycloadditions has garnered numerous attentions.On the other hand,enantioselec-tive functionalization of preformed four-membered carbocycles is emerging as an important complementary approach to access chiral cyclobutane de-rivatives with versatile structural patterns.Herein,we summarize recent advances in this field from 2012.To avoid undesired C—C bond cleavage driv-en by strain-releasing,it is crucial to choose compatible methods for enantioselective functionalization and meanwhile preserving intact four-membered ring skeleton.Guided by calculated hydrogenation enthalpies,which are used to evaluate the strain energy of indicated C—C bond,a clear picture of the developed methodologies on functionalization of four-membered carbocycles combining the strain energy and enhanced reactivity is presented.
