Organocatalytic Asymmetric Substitution Reaction And Cycloaddition Involving Ortho-Hydroxybenzyl Alcohols And 2?Indolylmethanols

In the first chapter,we introduced the recent background of catalytic asymmetric reactions of benzyl alcohols,and the goal and the contents of the research.In the second chapter,the first catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols with enamines was established,which afforded tetronic acid-derived diarylmethanes in considerable yields and good enantioselectivities?up to 89%yield,98:2 er?.This reaction not only provided an efficient method for the enantioselective synthesis of tetronic acid-derived diarylmethanes with biological relevance,but also fulfilled the task of developing catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols by using tetronic acid-derived enamines as competent nucleophiles.More importantly,the preliminary biological evaluation on some selected products revealed that this class of chiral tetronic acid-derived diarylmethanes exhibited strong cytotoxicity to HT-29,MCF-7 and TE-13 cancer cell lines.In the third chapter,the catalytic asymmetric[3+2]cycloaddition of 2-indolylmethanols with p-hydroxystyrenes was established in the presence of a chiral phosphoramide,and this reaction provided chiral cyclopenta[b]indole scaffolds in generally high yields and with good enantioselectivities?up to 98%yield,99:1 er?.The control experiments demonstrated that the dual hydrogen-bonding activation mode of the chiral catalyst toward the two substrates played an important role in the reaction.In addition,the large-scale reaction indicated that this catalytic asymmetric[3+2]cycloaddition could be scaled up for the synthesis of chiral cyclopenta[b]indole derivatives.In the fourth chapter,a catalytic aymmetric?-arylation of aldehydes using 2-indolylmethanols as arylation reagents has been established.This reaction was enabled by a cooperative catalytic system consisting of a gold complex,a Br?nsted acid and a chiral amine,which have a synergistic effect in the reaction process.By using this strategy,a series of?-arylation products of aldehydes were generated in overall acceptable yields and good enantioselectivities?up to 69%,91:9 er?.The control experiments demonstrated that the addition of PPh₃AuCl as a gold complex was helpful to improve the yield,and trifluoroacetic acid as a Br?nsted acid played a crucial role in the reaction by promoting the generation of carbocation and chiral enamine intermediates,which are two key intermediates of the aymmetric?-arylation reaction.In addition,the enantioselectivity of the reaction was mainly controlled by the chiral amine catalyst via forming a chiral enamine intermediate.This reaction has not only provided a useful protocol for catalytic aymmetric?-arylation of aldehydes,but also enriched the research contents of 2-indolymethanol-involved reactions and asymmetric cooperative catalysis.