Development of Highly Efficient and Selective Chirality Transfer Reaction

高效选择性手性转移反应的进展

• 批准号: 63570990
• 负责人: IBUKA Toshiro
• 金额: $ 1.41万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570990/
• 关键词: Organocopper; Transition Metal; Lewis Acid; Asymmetric Synthesis; Quaternary Carbon; 1,3-Chirality Transfer; S_N2' Reaction; Organocopper-Lewis Acid Complex; S_N2'反応; キラリティ; 不斉転位反応; 有機銅ールイス酸複合剤; 立体選択的合成

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

发展的合成方法，提供现成的手性碳中心的区域，化学和立体控制以及高水平的化学和光学产率代表了当代的挑战，合成有机化学家。最近，在酯及其同系物的α-烷基化中，通过手性金属烯醇化物、手性恶唑啉、环内和环外手性转移反应、不对称氢化、酶催化反应、σ-转移重排（如Ireland-Claisen重排）和α，β-烯酸酯的光去缀合，在对映体或非对映体选择性反应中取得了很大进展。带有（E）-双键的γ-烯酸酯是合成天然产物的有希望的中间体，因为受保护的（E）-烯丙醇和酯官能团可用于进一步的化学操作。然而，与上述有据可查的方法相反， ...更多信息 γ-甲磺酰氧基-（E）-或（Z）-α，β-烯酸酯与Me_2Cu（CN）Li_2·BF_3（制备的）反应，由MeLi-LiI的乙醚溶液制得）、MeCu（CN）Li·BF_3（由MeLi-LiBr的乙醚溶液制得）和RCu（CN）Li·BF_3（R = Et、n-Pr、n-Bu）在四氢呋喃或包括四氢呋喃的混合溶剂中在-78 ℃下反应，导致合成上有用的α-烷基-（E）-β，γ-烯酸酯的形成，这些化合物不容易通过其它方法获得。在所有情况下，化学产率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季碳中心。此外，还发展了一条以L-和D-酒石酸为原料，通过有机氰铜-三氟化硼配合物介导的1，3-手性转移反应合成保护的纯手性二乙烯基甲醇的有效路线。已发现化学产率和光学纯度非常高。产物的（E）-几何结构与起始物料的几何结构无关。在有机铜试剂中加入BF_3.Et_2O对1，3-手性转移是至关重要的。其他必要的因素，如反应溶剂，有机铜试剂的类型，和γ-含氧离去基团的性质进行了讨论。烷基化产物的β，γ-双键的（E）-几何结构可以通过使用手性位移试剂的^1H NMR光谱来确定。目前的1，3-手性转移策略是一个潜在的有用的方法，用于合成生物重要的化合物，如信息素，电子等静压，和抗生素。少

项目成果

山本嘉則: J.Am.Chem.Soc.,. 110. 617-618 (1988)

山本义典：J.Am.Chem.Soc.，110。617-618（1988）

山本嘉則、井深俊郎: "Recent Progress in Asymmertric Synthesis via Organocopper Compounds." GIT Fachz.Lab.32. 961-972 (1988)

Yoshinori Yamamoto、Toshiro Ibuka：“通过有机铜化合物进行不对称合成的最新进展。”GIT Fachz.Lab.32 (1988)。

井深俊郎,西井真二,山本嘉則: "A Convenient Synthesis of Four Stereoisomeric Methyl 2-Hydroxy-3-tert-Butyldimethylsiloxybutanoates from L-and D-Threonines.Versatile Chiral Building Blocks." Chemistry Express. 3. 53-56 (1988)

Toshiro Ibuka、Shinji Nishii、Yoshinori Yamamoto：“从 L-和 D-苏氨酸中方便地合成四种立体异构甲基 2-羟基-3-叔丁基甲硅烷氧基丁酸酯。多功能手性构建模块”3. 53-56（1988 年）。 ）

井深俊郎,斉藤真子,多賀徹,西井真二,新宮徹朗,山本嘉則: "New Stereoselective Synthesis of 20S and 20R Steroidal Side Chains.Remarkable Stereoselectivity Differences between Saturated and α,β-Unsaturated Steroidal Esters." J.Org.Chem.53. 3947-3952 (1988)

Toshiro Ibuka、Mako Saito、Toru Taga、Shinji Nishii、Tetsuro Shingu、Yoshinori Yamamoto：“20S 和 20R 甾体侧链的新型立体选择性合成。饱和和 α,β-不饱和甾体酯之间的显着立体选择性差异。” .53.3947-3952（1988）

Toshiro Ibuka, Tooru Taga, Tetsuro Shingu, Masako Saito, Shinji Nishii, and Yoshinori Yamamoto: "New Stereoselective Synthesis of 20S and 20R Steroidal Side Chains. Remarkable Stereoselectivity Differences between Saturated and alpha,beta-Unsaturated Ster

Toshiro Ibuka、Tooru Taga、Tetsuro Shingu、Masako Saito、Shinji Nishii 和 Yoshinori Yamamoto：“20S 和 20R 甾体侧链的新立体选择性合成。饱和和 α,β-不饱和立体之间显着的立体选择性差异