Development of Highly Efficient and Selective Chirality Transfer Reaction

开发具有高区域、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、手性恶唑啉、环内外手性转移反应、不对称氢化反应、酶催化反应、异型重排反应(如爱尔兰-克莱森重排)和α，β-烯酸酯的光去共轭反应，酯及其同系物的α-烷基化反应取得了很大进展。由于受保护的(E)-烯丙醇和酯功能都可用于进一步的化学操作，手性α-取代的含(E)-双键的β，γ-烯酸酯类化合物是合成天然产物的有希望的中间体。然而，与上面提到的有据可查的方法不同，…α-甲氧基-(E)-或(Z)-α，β-烯酸酯与Me_2Cu(CN)Li_2·BF_3的反应。在四氢呋喃或含四氢呋喃的混合溶剂中，在-78ﾟC时，可生成合成有用的α-烷基-(E)-β，γ-烯酸酯类化合物。在所有情况下，化学和光学产率都非常高。该方法可用于合成光学纯度很高的手性四元碳中心。此外，还开发了一条由L和D-酒石酸酯与有机铜-三氟化硼络合物催化的1，3-手性转移反应合成受保护的同手性二乙烯基甲醇的有效路线。化学产率和光学纯度都被发现异常高。产物的(E)几何构型与原料的几何构型无关。在有机铜试剂中加入BF_3、Et_2O是清洁的1，3-手性转移的关键。此外，还讨论了反应溶剂、有机铜试剂的种类和伽马氧基离开基团的性质等基本因素。烷基化产物的β，伽马双键的(E)几何构型可以通过使用手性位移试剂的~1H核磁共振波谱来确定。目前的1，3-手性转移策略是合成信息素、异构体和抗生素等生物重要化合物的一种潜在有用的方法。较少

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