Development of new organocatalysts and their applications in organic synthesis.

摘要

The work described in this dissertation focuses on three relevant parts. The first part concerns about the covalent bond mediated catalysis. In this part, novel amine organocatalysts for catalytic asymmetric reactions were designed and explored. We used a "privileged" structure-based strategy to quickly identify the effective pyrrolidine sulfonamide organocatalysts. An efficient method for synthesis of this class of catalysts has been developed. (S)-Pyrrolidine trifluoromethanesulfonamide was identified to be the efficient and general promoter with highly catalytic activity for a variety of organic reactions. It has been demonstrated for promotions of aldol reactions of alpha,alpha-dialkyl aldehydes with aromatic aldehydes to produce quaternary carbon-containing beta-hydroxy carbonyl compounds and alpha-sulfenylation of aldehydes and ketones. Moreover, a covalent bond mediated catalysis is exploited for organocatalytic Mukaiyama-Michael addition of silyl enol ethers to alpha, beta-unsaturated aldehydes using chiral imidazolidinone.;The second part of my dissertation deals with the noncovalent bond mediated catalysis by using hydrogen-bonds as activation forces. We have developed enantioselective Michael addition reactions of thioacetic acid with enones and trans-beta-nitrostyrenes. These processes are promoted by bifunctional chiral amine thiourea organocatalysts. Furthermore, we also have explored the enantioselective Michael addition reactions of fluorine-containing nucleophiles to trans-beta-nitrostyrenes. These processes, catalyzed by noncovalent bond catalysts-cinchona alkaloid derivatives, produce biologically and medicinally important chiral fluorine-containing compounds.;Finally, through rational and novel design of reactions and substrates, we have developed novel organocatalytic enantioselective tandem Michael-aldol/Michael reactions. These processes provide the most efficient approach to biologically and medically significant chiral thiobenzopyrans, benzopyrans and hydroquinolines. These reactions are catalyzed by chiral diaiylpyrrolinol silyl ethers between achiral 2-substituted benzaidehydes and alpha, beta-unsaturated aldehydes involving formation of new C-S, C-O, C-N and C-C bonds. We also have successfully explored the strategy for developing a novel organocatalytic, enantioselective domino Michael-Michael process. The reactions of alpha, beta-unsaturated aldehydes with ethyl 4-mercapto-2-butenoate, promoted by chiral diphenylprolinol TMS ether, give chiral tetrahydrothiophenes with generation of 3 new stereogenic centers.