Transition-Metal-Catalyzed Cross-Coupling Reactions Of Epoxides And Gem-Difluorinated Cyclopropanes

Transition-metal-catalyzed cross-coupling reactions for the construction of C(sp3)-C(sp3)/C(sp3)-B bonds has occupied a significant position in modern organic synthesis.Furthermore,it also plays vital role on C-F bond activation,and thus established newly developed synthetic methodologies for the construction of complex molecules.In the first chapter,we reviewed the history of the previously studies and the current status of transition-metal-catalyzed cross-coupling of simple epoxides and vinyl epoxides.In particular,ring-opening reaction of epoxides with carbon nucleophiles under catalytic conditions of various transition metals have been emphasized.In addition,borylative ring-opening of epoxide substrates have been involved in this chapter,and particular the obviously role of copper catalyst on this transformation is described.Furthermore,the cross-coupling reaction of fluorinated substituents,specially gem-difluorides and gem-difluorinated cyclopropanes have been illustrated.In general,the employment of transition metal in the cross-coupling reaction exhibited developed and practical strategies for the generation of C-C,C-B and C-X(X=N,O)as valuable compounds with generality of the reaction applications and clearly envision of reaction mechanism.Screening the pervious cross-coupling transformations of alkyl electrophiles(alkyl halides and pseudohalides),classic epoxides and gem-difluorinated cyclopropane as well,assumed the newly development methodologies utilizing copper and palladium catalysts.gem-diborylalkane reagents and epoxide substrates are considered as suitable compounds,which can be synthesized from inexpensive and commercially available reagents.In addition,epoxides are class of electrophile compounds which can be ring-opened with nucleophilic carbon to form new C-C bond compounds.Thus,in the second chapter,we realized copper-catalyzed opening reaction of epoxides with gem-diborylmethane.Aliphatic,aromatic epoxides as well as aziridines are converted to the corresponding y-pinacolboronate alcohols or amines in moderate to excellent yields.This new reaction provides beneficial application for classic epoxide substrates as well as interesting gem-diborylalkane reagents.Our new methodology has good functional group compatibility,which a large number of synthetic valuable functional groups could be tolerated and thus provided an efficient strategy under mild reaction conditions for the construction of complex structures.For instance,it includes a series of aliphatic and aromatic epoxides,which were converted to secondary or tertiary corresponding y-hydroxyl boronic esters.In addition,N-sulfonyl aziridines were also reacted in this transformation to afford the corresponding y-amino boronic esters.In the third chapter,we realized the first copper-catalyzed/mediated borylative ring opening reaction of epoxides.This process represents a direct borylative ring-opening of terminal epoxide substrates with readily available diboron reagents(B2pin2,B2neop2).A broad range of epoxide substrates with different functional groups were involved,and were subsequently converted to the corresponding ?-hydroxyl boronic esters.In addition,chiral epoxides were suitable substrates,which were then provided chiral retention 1,2-diols via additional oxidation step.The obtained product of ?-hydroxyl boronic esters have more applications in the organic reactions,e.g.the Suzuki-Miyaura cross-coupling was performed with aryl halides to give a variety of aryl-substituted secondary alcohols.And Chan-Lam-Evans cross-coupling reaction was also conducted with our products to afford arylated amine alcohols.Thus,the developed strategy proved that the ring-opening products(?-pinacol boronate alcohols)provided further beneficial approach for the formation of C-C and C-N bonds scaffolds.Palladium-catalyzed C-F bond activation of gem-difluorinated compounds via C-F bond cleavage are become appropriate approach to produce monofluorinated derivatives with excellent functional group compatibility.In the fourth chapter,we reported Pd-catalyzed regioselective activation of gem-difluorinated cyclopropanes induced by C-C bond cleavage.This protocol provides a general and efficient access to a variety of 2-fluoroallylic amines,ethers,esters,and alkylation products in high Z-selectivity,which are important skeletons in many biologically active molecules.This newly developed strategy was also useful in the synthesis of highly complex biologically relevant skeletons.In addition,the transformation represents the first general application of gem-difluorinated cyclopropanes as reaction partners in transition-metal-catalyzed cross-coupling reactions.Employment of 'copper&palladium catalysts' are introduced novel catalytic system in cross-coupling reaction.Moreover,they expanded the cross-coupling to involve ring-opening reaction of classic epoxides via C-C,C-B coupling reaction as well.Besides,they represented the first general application of ge/m-difluorinated cyclopropanes.Hence,these recently studies in our lab explained some difficult problems in traditional cross-coupling reactions of terminal epoxides and gem-difluorinated cyclopropane substrates that consider effecient efforts for new synthetic methods in modern organic chemistry.However,challenges remain,for instance,copper-catalyzed cross-coupling reaction of epoxides did not succeed to involve 1,2-substituation of epoxides and more substituted of bis(boronates),for construction useful compounds of quaternary carbon center.Therefore,our lab would devote further efforts to overcome these research complications.