T-BuOCl Promoted Decarboxylation Coupling And The Addition Of Carboxylic Acids With Alkynes

In the past decades,a rapidly growing number of decarboxylation coupling and alkyne functionalization in the formation of C-C and C-heteroatom bonds have attracted increasing attention.This type of reaction is a powerful protocol for the synthesis of natural products and drug active molecules with the advantages of high atom economy,high step economy and available raw materials.However,the requirements for a noble catalyst and harsh reaction conditions will greatly restrict the application of these reactions.Therefore,developing a new type of decarboxylation coupling and alkyne functionalization reactions under transition-metal-free conditions is highly desired.In the first part,the decarboxylative arylation reaction of 2-picolinic acids with arenes has been achieved under transition-metal-free conditions.The wide availability and simplicity of the starting materials,the mild conditions,the experimental simplicity,and the absence of a transition-metal catalyst make the present methodology highly useful in organic synthesis,especially in drug molecule synthesis.Under the optimized conditions,various 2-arylpyridines could be obtained in 45%-87%yields.This reaction exhibited good functional group tolerance,such as methyl,methoxyl,aryl,halides(Cl,Br),esters and nitro group.The mechanism study showed that the decarboxylative arylation of 2-picolinic acids underwent N-chloro carbene intermediates and C-H bond cleavage was not involved in the rate-determining step.In the second part,the decarboxylative halogenation reaction of 2-picolinic acids was successfully developed using dihalomethane as halogen sources under transition-metal-free conditions.The decarboxylative halogenation of 2-picolinic acids proceeded smoothly to afford 2-halogen-substituted pyridines in 35%-92%yields under the optimized conditions.This reaction exhibited good compatibility for many functional groups,such as methyl,aryl,halides(Cl,Br),esters and nitro group.The mechanism study showed that the decarboxylative halogenation of 2-picolinic acids also underwent a N-chloro carbene intermediates.Intermolecular competition reaction between dichloromethane and dibromomethane indicated that decarboxylative chlorination proceeded much easier than decarboxylative bromination.Probably because the formation of C-Cl bond is more favorable than the formation of C-Br bond in thermodynamics.In the last part,three-component radical addition of terminal alkynes,carboxylic acids,and tert-butyl hypochlorite was described.Under the optimized conditions,the gem-dichloro esters were obtained in 48%-95%yields with various of carboxylic acids and terminal alkynes.This reaction showed good tolerance for methyl,methoxyl,tert-butyl,halides(F,Cl and Br),trifluoromethyl,cyano group,and nitro group.The mechanism study indicated that the reaction underwent vinyl esters intermediates,which provided a possibility for the synthesis of enol ester.The prevailing decarboxylation of acyloxyl radicals is avoided in this process,which provides a new alternative strategy for the addition of acyloxyl radical to alkynes.