Organocatalytic Asymmetric Aldol Reaction Of Indole-3-carbaldehydes And Asymmetric Transfer Hydrogenation Of α-Keto Ketimines

Organocatalysis is a catalytic activation reaction strategy with metal-free organic molecules as catalysts.1970s, Hajos and Wiechert et al. first reported the proline-catalyzed intramolecular asymmetric aldol reaction. But after about 30 years, it has not attracted the concern of organic chemists. In 2000, Professor List published a research papers entitled "Proline-Catalyzed Direct Asymmetric Aldol Reactions", marking the revival of organcatalysis. In 2000, Professor Macmillan formally proposed the concept of "Organiccatalysis", it opened the golden age of Organiccatalysis. Organic asymmetric catalysis is uses the chiral small organic molecules as catalysts, and fast, efficiently and high enantioselectively achieve asymmetric synthesis of chiral organic chemistry transformation strategy. Compared with the metalcatalysis, organocatalysis possess some unique advantages such as nontoxic, inexpensive, mild reaction conditions, and insensitive to air and moisture.This dissertation focused on the studies of two chemical transformations of organic asymmetric catalysis, which included:1. Chiral Amino Acids-Catalyzed Asymmetric Aldol Reaction of Ketones with Indole-3-carbaldehydesWe rationally designed an efficient asymmetric aldol reaction of indole-3-carbaldehydes with ketones, catalyzed by O-TBS-protected L-threonine. All the products of the chiral 2-indolylmethanols and 3-indolylmethanols had good to excellent yields(28-96%), excellent enantioselectivities(92->99% ee), and good to excellent diastereoselectivities(54:46-98:2 dr). Hence, we established a new rout to synthesize chiral 3-substituted indoles.2. Chiral Brensted Acids-Catalyzed Asymmetric Transfer Hydrogenation of a-Keto KetiminesThe enantioenriched 1,2-amino alcohols structural motif is embedded in a vast array of biologically active molecules and key intermediates for synthesizing some Pharmaceuticals. Besides, enantioenriched 1,2-amino alcohols are usually used as chiral auxiliary groups, chiral ligands and resolving reagents in asymmetric synthesis. Perhaps the most straightforward means to produce enantioenriched 1,2-amino alcohols is the direct reduction of a-aminoketones. We rationally designed a reaction which is the benzothiazoline hydrogenation of a-Keto ketimines catalyzed by chiral BINOL-phosphoric acids. And this transformation to afford a-aminoketones in high yields(61-97%) with good to excellent enantioselectivities(90-96% ee). The reaction system is applied to the reductive amination of monoalkyl and 1,2-dialkyl-1,2-dione compound, and also to afford alkyl substituted a-aminoketones in high yields(67-93%) with good to excellent enantioselectivities(75-98% ee). Therefore, this work provided an efficient and straightforward route to synthetically chiral a-aminoketones and enantioenriched a, β-amino alcohols.