Transition Metal Catalyzed Thiocarbonyl-Assisted C-H Activated Amination Reaction

Organic sulfur compounds play an important role in life sciences,medicinal chemistry,materials science and other fields.Functional modification of sulfur-containing compounds can further enrich their types and expand their application fields.In the past ten years,transition metal-catalyzed C-H bond activation functionalization has developed rapidly.The construction of C-N bonds and C-X(X=C,S,P,etc.)by activating C-H bonds has become an important tool in organic synthetic chemistry.And directing group-assisted C-H functionalization is widely used in organic synthetic chemistry.Thiocarbonyl group-containing compounds have been less thoroughly investigated as directing groups due to sulfur’s ability to poison many transition-metal catalysts.With the help of C-H activation functionalization as a powerful synthetic tool,the amination modification of thiocarbonyl group-containing compounds and the direct amination modification of drug molecules and bioactive molecules in the late stage can provide an efficient strategy for the construction of potential bioactive molecular library and the exploration of new bioactive molecules.The content of this thesis is the transition metal catalyzed thiocarbonyl assisted C-H aminations,which consists of three parts as follows:Part Ⅰ:We summarized the functionalization reaction of sulfur-containing directing groups and the C-H amination reaction of different directing groups.Part Ⅱ:The Co(Ⅲ)-catalyzed C-H amination of N,N-dialkyl thiobenzamides with 3-phenyl1,4,2-dioxazol-5-one using thioamides as directing groups under mild conditions has been achieved.Deuteration kinetic experiments verified that C-H bond activation is the ratedetermining step of the reaction.And the developed methodology has been applied to the synthesis of the derivatives of adapalene,a drug for acne,which further expands the application of this reaction.Part Ⅲ:Rh(Ⅲ)-catalyzed C-H amination reaction of ferrocenes has been developed by using 3-phenyl-1,4,2-dioxazol-5-one as the amination reagent under the assistance of the thiocarbonyl group.The reaction proceeds with high functional group tolerance.The strategy was applied to the late-stage functionalization of the anti-inflammatory drug isoxepac,the drug probenecid for gout and hyperuricemia,and the drug gemfibrozil for hyperlipidemia,which provide a new way to explore new drugs.