Cobalt-Catalyzed C-H Activation And Carbonylation Or Isocyanide Insertion For The Synthesis Of Amide Derivatives

Amides are one of the most typical and common functional groups,which are found in many pharmaceuticals,natural products,and bioactive molecules.Therefore,the development of green,efficient and highly atomic economical methods for amides synthesis is of great significance to biology,pharmacology and medicine.Transition-metal-catalyzed carbonylation has become one of the most efficient and straightforward methods for the synthesis of amide derivatives,which has made outstanding contributions to the construction of the frameworks of pharmaceuticals.In addition,Isocyanide insertion reaction has emerged as a facile method for the synthesis of amide derivatives in recent years,while limited examples have been reported.This thesis focuses on C-H activation and carbonylation or Isocyanide insertion to access amide derivatives:A Cobalt-catalyzed C-H activation and carbonylation of N-（2-vinylphenyl）-picolinamides has been developed for the construction of（NH）-quinolin-2（1H）-one scaffolds.In this reaction,various free（NH）-quinolin-2（1H）-ones were produced in good yields（up to 92%）by employing Benzene-1,3,5-triyltriformate（TFBen）as the CO source and Picolinamide as the traceless directing group.Moreover,several modifications of（NH）-quinolin-2（1H）-ones were performed.A Cobalt-catalyzed C-H activation and carbonylation of Tryptamine derivatives has been developed for the synthesis of free（NH）-tetrahydro-β-carbolinones.This reaction employed a Cobalt（II）salt as the non-noble catalyst with TFBen as the CO source,and a variety of free（NH）-tetrahydro-β-carbolinones were produced in good yields using a traceless directing group strategy.Furthermore,late-stage modifications of several bioactive molecules（Sorbic acid,Probenecid,and Febuxostat）could also be realized.In addition,silver carbonate as the oxidant could be recycled and reused.A Cobalt-catalyzed C-H activation and isocyanide insertion of Tryptamine derivatives has been developed for the construction of 1H-indole-2-carboxamide scaffolds.This reaction employed a Cobalt（II）salt as the non-noble catalyst and Ag₂CO₃as the oxidant,producing a variety of free 1H-indole-2-carboxamides rapidly and efficiently.Moreover,several modifications of 1H-indole-2-carboxamides were performed.In addition,the mechanistic experiments showed the Cobalt（III）complex was the active species in this catalytic cycle.