Cycloaddition Reactions Of Indolyl Benzylic Alcohols With Indolyl Acrylic Esters Catalyzed By Chiral Phosphoric Acids

Pyrrolo[1,2-a]indoles bearing three rings represent the important structural feature of biologically active natural products and pharmaceutical compounds. The challenging structural and stereochemical features as well as their interesting biological activities of these compounds have aroused the interesting of many researchers toward the synthesis of pyrrolo[1,2-a]indoles. In the dissertation, the [6+2] cycloaddition reactions between indolyl benzylic alcohols and indolyl acrylic esters, catalyzed by chiral phosphoric acids, were studied; The derivatives of pyrrolo[1,2-a]indoles were synthesized in a highly regio-and stereoselective manner, providing a new method for the preparation of this kind of chiral compounds.This thesis consists of three chapters. The first chapter is a review, which is mainly about the research progress for the synthese of indole derivatives and applications of chiral phosphoric acids in asymmetric synthesis.In the first section of the second chapter, the syntheses of several chiral phosphoric acids were described, and they were used as catalysts in the following reaction; the preparations of the substrates, the secondary benzylic alcohols bearing indolyls and the indolyl acrylic esters, were described in the second section.In the third chapter, we explored the cycloaddition reaction between an indolyl benzylic alcohols and an indolyl acrylic ester catalyzed by chiral phosphoric acid, and found the [6+2] cycloaddition reaction occurred leading to the formation of pyrrolo[1,2-a]indoles with generation of three contiguous stereocenters. The reaction of a phenyl methanol bearing3-methyl indolyl (7a) and ethyl3-(1H-indol-3-yl)-acrylic acid ester (11a) was used to optimize the reaction conditions, and the best result was obtained when the reaction proceeded in toluene at0℃catalyzed by the chiral phosphoric acid1d, while the reaction gave high yield (90%) and stereoselctivity (dr≥20:1, ee≥91%). Then, under this optimized conditions, the reactions of the secondary alcohol7a (or7b) with several α, β-unsaturated esters (lla-llf) catalyzed by chiral phosphoric acid Id were studied. The moderate to high yields(59％～91％)and stereoselctivities(dr9:1～20:1,ee68％～93％) were obtained...