Studies On The Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis Of Compounds Containing Chiral C–X Bonds

Asymmetric catalysis has emerged as a robust and meaningful frontier in the field of organic chemistry,one of the main tasks in this area is the synthesis and application of the catalysts.Along with the development in this area,emerged a series of small molecule organocatalysts.Among which,a critical branch of asymmetric organocatalysis,more and more people began to pay attention to Br?nsted acid catalysis.Chiral phosphoric acids,based on its high catalytic activity,extensive scope of application and low cost,has been extensively studied and widely used in different types of asymmetric catalysis reactions.This dissertation is mainly focused on the synthesis of different types of chiral phosphoric acids and their applications in asymmetric catalysis.The enantioselective hydrogenation of 3-aryl-1,4-benzoxazines and 2-aryl quinolines have been developed employing SPINOL-derived phosphoric acid.The products 3-aryl-dihydro-2H-1,4-benzoxazines and tetrahydroquinolines were obtained in high yields(up to 99%)and enantioselectivities(up to >99%).The asymmetric hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-ones has been developed employing SPINOL-derived phosphoric acid.Under the optimal reaction conditions of 9-anthracenyl substituted SPINOL-derived phosphoric acid,tbutyl substituted hansztch ester,toluene,50 ?,the products 3-aryl-isoindolin-1-ones were obtained in high yields(up to 98%)and enantioselectivities(up to 93%).The enantioselective reduction of ?-hydroxy ketones with catecholborane has been developed employing a 1,1?-bi-2-naphthol(BINOL)-derived ion-pair organocatalyst.The products aromatic 1,2-diols were obtained in high yields(up to 90%)and enantioselectivities(up to 97%).The absolute configuration of the product was confirmed to be S by comparing the optical rotation with the literature.On the basis of experimental results and previous reports,a possible mechanism was proposed.The asymmetric catalytic insertion of ?-diazoesters into the O–H bond has been developed employing a rhodium(II)/chiral phosphoric acid system.Using 9-anthracenyl substituted BINOL-derived phosphoric acid as catalsyst,the products generated from O–H insertion of carboxylic acids were obtained in high yields(up to 85%)and enantioselectivities(up to 95%).Using 9-phenanthrenyl substituted BINOL-derived phosphoric acid as catalyst,the products generated from O–H insertion of alcohols were obtained in high yields(up to 87%)and enantioselectivities(up to 90%).Using 1-naphthyl substituted SPINOL-derived phosphoric acid as catalyst,the products generated from O–H insertion of phenols were obtained in high yields(up to 96%)and enantioselectivities(up to 97%).The absolute configuration of the products was confirmed to be S by X-ray single-crystal analysis.To further disclose the mechanism of asymmetric O–H insertion of carboxylic acid,we performed the density functional theory(DFT)calculations.The reaction pathway affording the product with S configuration is more favorable both dynamiclly and thermodynamiclly.This is in consistent with our results of X-ray single-crystal analysis.The synthesis and resolution of 2,2'-dihydroxy-4,4'-dimethyl-3,3'-bipyridine has also been developed.The racemic 2,2'-dimethoxy-4,4'-di methyl-3,3'-bipyridine was prepared in three steps from 2-chloro-3-amino-4-methylpyridine via methoxylation,Sandmeyer bromination and Ullmann reaction,with an overall yield of 25%.Then it was resolved by(+)-dibenzoyltartaric acid,the resulting(R)-2,2'-dimethoxy-4,4'-dimethyl-3,3'-bipyridine could be obtaind in 99% ee.