Study On Diverse C-H Functionalization Of Thioamides And Their Novel Cascade Reaction With Carbenes

Heterocycles containing nitrogen and/or sulfur exist widely in medicines,pesticides,food additives and materials.The non-toxic,odorless,safe and easily available sulfur-containing starting materials are one of the bottlenecks for the construction of diverse poly-functional sulfur-containing heterocyclic compounds.In this paper,we synthesized N-alkyl-N-aryl thioamides bearing two ester functional groups at?-carbon of thiocarbonyl from safe and non-toxic reagents,and a series of novel reactions with N-alkyl-N-aryl thioamides as precursors of thioenals has been studied and developed.This paper consists of two parts.The first part is the study on switchable regio-and chemoselective intramolecular C-H functionalization reaction of N-alkyl-N-aryl thioamides,and the second part is the novel cascade reaction of N-alkyl-N-aryl thioamides with carbenes.In the first part,the swichable regio-and chemoselective intramolecular thioenolization/C-H thiolation and C(sp²)-H/C(sp³)-H dehydrogenative coupling of N-alkyl-N-aryl thioamides has been developed through the use of the same Co Br₂ catalyst by changing the temperature,oxidants and the use of base or not,providing 2-methylene-2,3-dihydrobenzo[d]thiazoles and thio-oxindoles efficiently with high chemoselectivities.Both mild transformations from the same precursors are step-and atom-economy with a wide range of substrates and good functional group tolerance.In addition,the mechanism for the two C-H functionalization has also been fully studied to explain the origin of high regio-and chemoselectivities.In the second part,a novel cascade reaction of N-alkyl-N-aryl thioamides bearing easters with N-tosylhydrazones was developed under the conditions of Pd(TFA)₂ as a catalyst,^tBu Xphos as a ligand,and Na O^tBu as base,and BF₃·Et₂O,providing poly-functional thiophene-3(2H)-ones with moderate to good yields.In this novel cascade reaction,metal carbene was generated in situ from the carbene precursor N-tosylhydrazones under the conditions of Pd(TFA)₂,^tBu Xphos,and Na O^tBu.BF₃·Et₂O or Pd(TFA)₂promotes the thioenolization of N-alkyl-N-aryl thioamides,then the generated thioenol intermediate attack the in situ generated metal carbene,followed by cyclization through the cascade addition-elimination of the BF₃·Et₂O-activated intramolecular ester groups,providing the desired poly-functional thiophene-3(2H)-ones with moderate to good yields.