The development and synthetic studies of modified cinchona alkaloids as chiral organic catalysts for asymmetric nucleophile-electrophile reactions

We have developed the first highly enantioselective and general nonenzymatic catalytic method for the asymmetric alcoholysis of prochiral and meso cyclic anhydrides mediated by readily available monomeric and dimeric derivatives of cinchona alkaloids. This study also provides the first example of the remarkable effectiveness of readily available modified cinchona alkaloids as organic catalysts for asymmetric nucleophile-electrophile reactions.; We have developed a new catalytic method for the synthesis of optically active succinnate mono esters via a highly efficient parallel kinetic resolution process, which involves two simultaneous enantioselective and divergently regioselective alcoholyses of two enantiomers of the mono substituted succinnic anhydrides promoted by a common biscinchona alkaloid derivative. This is the first efficient catalytic parallel kinetic resolution of racemic bifunctional substrates mediated by a single organic catalyst.; A highly efficient, asymmetric synthetic route for the chiral quinol 3.69, an advanced intermediate towards the asymmetric synthesis of trichodimerol, was developed. The absolute stereoconfiguration of 3.69 is defined using the recently developed asymmetric cyanosilylation of α,α-dialkoxy ketones method.; We have developed the first general and highly enantioselective catalytic asymmetric 1,4-addition of thiols to cyclic enones with modified cinchona alkaloid. Enantiomeric excesses ranging from 92 to >99% was accomplished for 5- to 9-membered enones. These results also extend the scope of chiral Lewis base catalysis of modified cinchona alkaloid to a new class of important reaction.; In summary, modified cinchona alkaloids have been developed as highly effective and broadly useful organic catalysts for several important asymmetric nucleophile-electrophile reactions. These newly developed reactions could be used for asymmetric synthesis in both research and industrial scale. These developments contribute significantly to a major expansion of the already remarkably broad scope of asymmetric catalysis of cinchona alkaloids.