Applications Of Metal Catalyzed C-H Bonds Activation In The Synthesis Of Pharmaceutically Active Units

Carbon-carbon bonds and carbon-heteroatom bonds formation reactions are one of themost important researches in the pharmaceutical synthesis. A novel highly efficient andselective new reaction and approach for forming C-C and C-X bonds will greatly improve theefficiency of the synthesis of the target products. So it can make a positive impact on thedevelopment of modern drug molecules synthesis, which is of great theoretical significanceand application value. Currently, the direct construction of the C-C bond and C-X bondthrough the transition metal catalyzed C-H bond activation has become a hot topic in organicsynthesis, due to their short steps, less waste emissions and atom economy properties.In this thesis, we foucus on the gold and iron-catalyzed sp3C-H activation reactions,which are greatly useful synthetic routes and have been used in the construction of someimportant active unites of biological activity. The protocols provide a simple, efficient pathfor the synthesis of drug molecules. Moreover, it also provides a theoretical basis for themetal-catalyzed asymmetric synthesis in the latter study. The research work of this thesisincludes:1. Gold-Catalyzed Direct Indolation of TetrahydroisoquinolinesIndoles are very important nitrogen-containing compounds. As a multifunctionalstructural unit, it plays an very important role in the synthesis some significant potentialbiological active compounds. Therefore, development of a novel, efficient, high selectivity,environmentally friendly methodology for the synthesis of indole derivatives has arousedgreat interest in recent yeas. In the paper, we have developed a mild, efficient strategy for theoxidative cross dehydrogentative coupling of indoles with N-aryl tetrahydroisoquinolinesusing NaAuCl4as catalyst and TBHP as oxidant. The reaction is compatible with a wide rangeof substituted indoles, to enable the formation of various alkylated heteroarenes under verymild reaction conditions. The advantages of this methodology are larger substrate scope, highregioselectivity, synthetic simplicity and moderate reaction conditions.2. Iron-catalyzed aerobic phosphonation of sp3C–H bondsPhosphorus-containing compounds, especially the-Aminophosphonates and thecorresponding a-aminophosphonic acids are the precursor of many biologically activemolecules. They have received much interest in organic and medicinal chemistry due to theirsimilar structure with natural and unnatural amino acids. In the paper, we developed anefficient cross-dehydrogenative-coupling (CDC) between sp3C-H bond adjacent to a nitrogenatom of tertiary amine and H-P bonds of dialkyl phosphites and some diaryl phosphates usingFeCl3as catalyst and Air as oxidant under mild reaction conditions. It has been found that asafe, convenient, environmental and efficient methods to synthesize a series of importantbioactive-aminophosphonates.