Copper-catalyzed C-H/N-H Cross Dehydrogenative Coupling Between Amides And Simple Ethers

The construction of C-N bond is of great importance as nitrogen-containing compounds are found in numerous natural products,biological active compounds,organic synthetic intermediates and functional materials.In recent years,significant progress has been made towards the C?sp2?-N bond formation through transition-metal-catalyzed C-H activation.However,facile and efficient methods for formation of C?sp3?-N bonds were less developed.Cross dehydrogenative coupling?CDC?reaction has emerged as an useful tool for the atom-economical and step-economical construction of new C–C and C–heteroatom bonds between C-H and another C-H or X-H?X=O,S,N etc.?bond,which is in accord with the requirement of green chemistry.Ethers are common organic compounds and are often used as solvents.The cross dehydrogenative coupling reaction of the ether's ?-C-H bond with the amide N-H bond can efficiently construct the C?sp3?-N bond.In this thesis,an efficient copper-catalyzed ?-C-H amidation of simple ethers with N-?8-quinolyl?amides through C-H/N-H cross dehydrogenative coupling was developed.The reaction proceeded in the presence of Cu?OAc?₂?20 mol%?,4-methylpyridine?20 mol%?,TBHP?2.5 eq?in THF?2 m L?stirring under air at 65 ? for 8 h.Chelation assistance was employed for the formation of an active copper amide species which can couple with the ?-carbon-centered radical generated form simple ethers.This method was applicable to both alkyl and aryl amides as well as various cyclic and acyclic ethers.It also possessed the merit of air and moisture tolerance.A highly efficient copper-catalyzed C-H/N-H cross dehydrogenative coupling between picolinamides and simple ethers was also developed.The reaction was promoted by the chelation assistance and exhibited highest TON of 345 and highest TOF of 400?h-1?.The reaction proceeded in the presence of Cu?OAc?2?5 mol%?,4-methylpyridine?5 mol%?,TBHP?3.5 eq?in THF?2 m L?stirring under air at 25 ? for 8 h.This method was applicable to both N-aryl and alkyl picolinamides as well as various cyclic and acyclic ethers with good functional group compatibility.It also possessed the merit of air and moisture tolerance and easy operation.It will provide a novel and efficient route for the preparation of N-substituted amino alcohols,which can be easily transformed to other useful compounds.