Development of Highly Efficient and Selective Chirality Transfer Reaction

开发具有高水平的区域、化学和立体控制以及高化学和光学产率的手性碳中心的合成方法是合成有机化学家面临的当代挑战。近年来，通过手性金属烯醇酸酯、手性唑啉、环内和环外手性转移反应、不对称氢化反应、酶催化反应、异位重排（如爱尔兰-克莱森重排）和光解偶联，酯及其同族物在对映或非对映选择性反应中的烷基化反应取得了很大进展。手性取代的带(E)-双键的δ -氧合β， -烯酸盐是合成天然产物的有前途的中间体，因为保护(E)-烯丙醇和酯功能都可用于进一步的化学处理。然而，与上述文献记载的方法相反，更多的手性合成这样的-烷基-(E)- β， γ -烯酸盐仍然是一个挑战。-甲氧基-(E)-或(Z)- α， β -enoates与Me_2Cu(CN)Li_2的反应。BF_3(准备。源自MeLi-LiI in ether), MeCu(CN)Li。BF_3（由MeLi-LiBr在醚中制备）和RCu(CN)Li。BF_3 （R = Et, n-Pr, n-Bu）在四氢呋喃或含有四氢呋喃的混合溶剂中，在- 78℃的温度下生成合成有用的α -烷基-(E)- β， γ -烯酸酯，这些化合物不易通过其他方法获得。在所有情况下，化学和光学产量都非常高。该方法可用于合成光学纯度很高的手性季碳中心。此外，还建立了以L-酒石酸盐和d -酒石酸盐为原料，以三氟化铜-三氟化硼配合物介导1,3-手性转移反应合成保护型二乙烯基甲醇的高效途径。化学收率和光学纯度均很高。产品的(E)几何形状与原料的几何形状无关。添加BF_3。Et_2O到有机铜试剂对1,3-手性的干净转移至关重要。讨论了反应溶剂、有机铜试剂类型、氧化离去基性质等因素。烷基化产物的β， γ -双键的(E)几何结构可以用手性移位试剂的^1H NMR谱测定。目前的1,3-手性转移策略是一种潜在的有用的方法，用于合成生物学上重要的化合物，如信息素，等糖和抗生素。少

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