Research Of Enantioselective Synthesis Of Triarylmethanes By Biaxially Chiral Imidodiphosphoric Acids Catalyzed Friedel–Crafts Reactions

Enantioselective Friedel–Crafts reaction is one of the most important reactions on construction of enantioenrich aromatic derivatives. We have developed enantioselective synthesis of four different types of tertiary and quaternary carbon stereocentered triarylmethanes, which was accomplished by chiral imidodiphosphoric acids catalyzed Friedel–Crafts reaction of vinyliminium precursors with pyrroles and indoles. This dissertation consists of three chapters as follows:Chapter 1: This chapter firstly introduced recent development in the field of enantioselective Friedel–Crafts reaction. Secondly, the development of chiral Br?nsted acids was summarized and the design and development of chiral imidodiphosphoric acids(IDPAs) were introduced. At last, we described the enantioselective reactions on vinylogous iminium ions catalyzed by chiral Br?nsted acids.Chapter 2: Two parts were contained.Part 1, the wide application of triarylmethanes in pharmacueticals and materials was first introduced. In addition, previous work on enantioselective synthesis of triarylmethanes was also summarized. Second, enantioselective synthesis of tertiary carbon centered 1-aryl-1-indolyl-1-pyrrolylmethanes was elaborated, which was accomplished by enantioselective Friedel–Crafts reaction of trimethylsilyl-protected 3-arylindolylmethanols with pyrroles catalyzed by chiral IDPAs. At optimized conditions, 19 examples were completed with excellent chemo- and enantioselectivity(up to 99% yield, up to 96% ee) by utilizing low catalyst loadings(as low as 1 mol%). Additionally, this process was amenable to gram scale synthesis. It is of importance to utilize the trimethylsilyl protection group on 3-arylindolylmethanols.Part 2, enantioselective synthesis of tertiary carbon centered 1-aryl-1,1’-bisindolylmethanes was accomplished by enantioselective Friedel–Crafts reaction of trimethylsilyl-protected 3-arylindolylmethanols with N-methylindoles catalyzed by chiral IDPAs. At optimized conditions, 14 examples were completed with high yield(up to 99%) and excellent enantioselectivity(up to 95% ee) with 1 mol% catalyst. The absolute configuration was established to be R.Chapter 3: Two parts were contained.Part 1, bioactivity of 3,3-diaryloxindoles was first introduced. In addition, previous work on enantioselective synthesis of quaternary carbon centered triaylmethanes was also summarized. Second, enantioselective synthesis of quaternary carbon centered 3-indolyl-3-pyrrolyloxindoles has been elaborated, which was accomplished by Friedel–Crafts reaction of 3-hydroxy-3-indolyloxindoles with pyrroles catalyzed by chiral IDPAs. At optimized conditions, 14 examples were completed in excellent yield(up to >99%) with high enantioselectivity(up to 98% ee) by 2.5 mol% catalyst. The absolute configuration was established to be R. Although pyrroles contain several competitive nucleophilic sites and feature more difficult enantiofacial discrimination, highly enantioselective mono-alkylation of pyrroles has been realized.Part 2, enantioselective synthesis of quaternary carbon centered 3,3-bis(indol-3-yl)oxindoles has been accomplished by Friedel–Crafts reaction of 3-hydroxy-3-indolyloxindoles with N-methylindoles, which was catalyzed by chiral IDPAs. The substitutents bearing differently electronic properties at 5, 6 and 7-positions of oxindoles and indoles showed high adaptation under optimized conditions. At optimized conditions, 23 examples were completed in excellent yield(up to >99%) with high enantioselectivity(up to 98% ee) by low catalyst loadings(as low as 0.5 mol%). This process was amenable to gram scale synthesis. The absolute configuration was established to be S.