Difluoroalkylation Via Visible-Light Photoredox Catalysis

The incorporation of difluorinated functional groups into organic molecules has been widely recognized as a general strategy in pharmaceutical research and drug development. For these reasons, substantial effort has been devoted to the development of synthetic methods for the assembly of difluorinated small molecules. However, methods for the synthesis of difluoroalkylation remain limited. Since they often require higher reaction temperature, overload base or alkali metal, there are some defects in the compatibility of substrates, as well as the inconvenience in making use of these methods. In the meantime, visible light catalysis, as a safe, cheap and renewable source of chemical energy, has emerged recently as a powerful theme in organic chemistry. Herein, we speculated methods in view of visible-light-driven difluoroalkylation using BrF2COOEt as the CF2 radical source, which provides a facile approach to potential biological difluorinated heterocyclic.This thesis includes two parts:In the first part, we have developed a highly efficient and practical approach for the preparation of CF2-containing 3,4-disubstituted dihydroquinolin-2(1H)-one derivatives as well as l-azaspiro[4.5]-decanes by visible-light-induced difluoromethylation of an N-arylcinnamamide reaction with Br2COOEt under mild conditions. The method described represents one of the most powerful routes for its operational simplicity, low catalyst loading, and less additives, and further extends the application of photochemistry in the realm of organic synthesis.In the second part, tandem difluoroalkylation and C-C coupling via Visible-Light Photoredox Catalysis were further studied. We have developed the method to construct the core framework of azaspiro and chromone with medium yields and general chemoselectivities. And also, we expanded the range of substrates, and investigated the influence of electrical and other factors on the reactions. This reaction is practical and useful in the synthesis of nature products and drug analogues.