Development of Highly Efficient and Selective Chirality Transfer Reaction

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Development of synthetic methods which provide ready access to chiral carbon centers with a high level of regio-, chemo-, and stereo-control as well as high chemical and optical yields represents a contemporary challenge for synthetic organic chemists. Recently, great advances have been made in the alpha-alkylation of esters and their congeners in enantio- or diastereoselective reactions via chiral metal enolates, chiral oxazolines, intra- and extraannular chirality transfer reactions, asymmetric hydrogenations, enzyme-catalyzed reactions, sigmatropic rearrangements such as the Ireland-Claisen rearrangement, and photodeconjugation of alpha,beta-enoates.Chiral alpha-substituted delta-oxygenated beta,gamma-enoates bearing an (E)-double bond are promising intermediates for the synthesis of natural products since both protected (E)-allylic alcohol and ester functions are available for further chemical manipulation. However, in contrast to the well documented methodologies mentioned above, … More chiral syntheses of such a- alkyl-(E)-beta,gamma-enoates remain a challenge.Reaction of gamma-mesyloxy-(E)- or (Z)-alpha, beta-enoates with Me_2Cu(CN)Li_2.BF_3 (prepared. from MeLi-LiI in ether), MeCu(CN)Li.BF_3 (prepared from MeLi-LiBr in ether), and RCu(CN)Li.BF_3 (R = Et, n-Pr, n-Bu) in tetrahydrofuran or mixed solvents involving tetrahydrofuran at - 78ﾟC results in the formation of synthetically useful alpha-alkyl-(E)-beta,gamma-enoates, compounds that are not easily accessible by other means. In all cases the chemical and optical yields are very high. The method can be applied to the synthesis of chiral quatemary carbon center with very high optical purity. Furthermore, an efficient synthetic route of protected homochiral divinylmethanols from L- and D-tartrates with organocyanocopper-boron trifluoride complexes mediated 1,3-chirality transfer reaction has been developed. The chemical yield and optical purity have been found to be unformly very high. The (E)-geometry of the product is not related to the geometry of the starting material. Addition of BF_3.Et_2O to the organocopper reagent is critical to the clean 1,3-chirality transfer. Other essential factors such as reaction solvent, type of organocopper reagent, and nature of the gamma-oxygenated leaving group are discussed. The (E)-geometry of the beta,gamma-double bond of the alkylation products could be determined by ^1H NMR spectroscopy using a chiral shift reagent. The present 1,3-chirality transfer strategy is a potentially useful method for the synthesis of biologically important compounds such as pheromones, isostares, and antibiotics. Less