Development of an Efficient "Chiral Technology" Based on the Chiral Coordinating Agent Protocol

基于手性配位剂协议的高效“手性技术”的开发

• 批准号: 08555221
• 负责人: NAKAI Takeshi
• 金额: $ 4.35万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08555221/
• 关键词: Enantiocontrol; Chiral ligand; Carbanion reaction; Carbanion cyclization; [2,3] -Wittig rearrangement; [1,2] -Wittig rearrangement; 不斉合成; 不斉リチオ化

1. Enantioselective S_E2 Reaction of alpha-Methoxy Benzyllithium Generatedvia t-BuLi/Chiral Bisoxazoline System In recent years the extemal chiral ligand (ECL) -based asymmetric lithiation/S_E2 reaction has emerged as an efficient strategy for enantioselective C-C bond formations. While most of the successes so far have been made using (-) -sparteine as ECL,the development of other ECL's effective for different reactions is a significant challenge. We have developed the highly enantioselective S_E2 reactions of alpha-methoxy benzyllithium generated via the lithiation (deprotonation) with t-BuLi complexed with the chiral bisoxazoline, (S,S) -Box-i-Pr, as ECL (Lc^*). Of special interest is the reaction with the acetylenic aldehyde which affords the 1,2-diolmonomethyl ether with an extremely high % ee along with a relatively high anti diastereoselectivity.2. Carbanion Cyclization : Absolute Stereochemistry and Enantiocontrol The carbanion cyclization of 5-alkenyllithiums and their hetero … More analogues has emerged as an efficient method for stereoselective carbocyclization. We have investigated the absolute stereochemistry of the carbanion cyclization and the developed the its enantioselective version.Absolute Stereochemistry of Carbanion Cyclization : Treatment of enatiomerically defined (R) -alpha-alkenyloxystannanes with n-BuLi at -78ﾟC was found to afford the cyclization product (S) in high stereoselectivity. Tus the rearrangement is proved to proceeds with completely retention of configuration at the Li-bearing chiral center.Enantioselective Version of Carbanion Cyclization : Upon treatment with (-) -sparteine / s-BuLi, alkenylcarbamate gave cyclopentane in a high enatioselectivity, along with 6-phenylbicyclo [3.1.0] hexane. More significantly, a similar cyclization of the 4-silyloxy substrate (racemic) was found to afford the silyoxy cyclopentane and the 2-silyloxy bicyclohexane of which the absolute configurations are opposite each other.3. Enantioselective [2,3] -Wittig Rearrangement Induced by Asymmetric Lithiation with t-Butyllithium/Chiral Bisoxazoline System The [2,3] -Wittig rearrangement, particularly its asymmetric version using enantio-enriched substrates, enjoys wide spread application in many facets of organic synthesis. However, only a few examples have been reported of the enantioselective version that permit direct access to an enantio-enriched product from an achiral substrate. In view of the recent progress in the asymmetric lithiation protocol, we became intriguted by the exploration of enantioselective [2,3] -Wittig variants induced by the ECL-based asymmetric lithiation protocol. Now we have developed the highly enantioselective [2,3] Wittig rearrangement using the chiral bisoxazoline ((S,S) -Box-i-Pr) / t-BuLi system. This is the first example of the utilization of a chiral bisoxazoline as ECL for the enantioselective [2,3] -Wittig rearrangement. Less

1.t-BuLi/手性双恶唑啉体系生成的α-甲氧基苄基锂的不对称S_E_2反应近年来，基于外部手性配体的不对称锂/S_E_2反应已成为一种形成不对称C-C键的有效策略。虽然到目前为止，大多数的成功都是使用(-)-司马豆碱作为ECL，但开发其他有效的ECL对不同的反应是一个巨大的挑战。本文报道了α-甲氧基苄基锂与手性双恶唑啉络合物(S，S)-盒-I-Pr经锂(去质子化)反应生成的高对映选择性的β-甲氧基苄基锂(Lc^*)的S_E2反应。特别令人感兴趣的是与乙烯醛的反应，它提供了具有极高的ee%以及相对较高的反对映选择性的1，2-二烯基单甲醚。碳负离子环化：绝对立体化学和对映体控制5-烯基锂及其杂化…的碳负离子环化更多的类似物已成为立体选择性碳环化的有效方法。我们研究了碳负离子环化的绝对立体化学，并开发了它的对映选择性版本。碳负离子环化的绝对立体化学：在-78ﾟC用n-BuLi处理对映体定义的(R)-α-烯基氧杂环丁烷可以得到高立体选择性的环化产物(S)。该重排反应完全保持了含锂手性中心的构型。对映体选择性的碳负离子环化反应：在(-)-雀花碱/S-丁二酸锂作用下，氨基甲酸烯基酯与6-苯基双环[3.1.0]己烷一起得到了高对映选择性的环戊烷。更重要的是，4-硅氧基底物(外消旋)的类似环化反应得到了绝对构型相反的硅氧基环戊烷和2-硅氧基二环己烷。叔丁基锂/手性双恶唑啉体系不对称锂离子诱导的不对称[2，3]-Wittig重排反应[2，3]-Wittig重排反应在有机合成中有着广泛的应用，尤其是它的不对称重排反应。然而，只有几个例子报道了允许从非手性底物直接获得富含对映体的产物的对映体选择性版本。鉴于不对称锂离子交换协议的最新进展，我们对基于ECL的不对称锂离子交换协议诱导的对映体选择性[2，3]-Wittig变体的探索产生了兴趣。现在，我们利用手性双恶唑啉((S，S)-盒-i-Pr)/t-BuLi体系发展了高对映选择性的[2，3]Wittig重排反应。这是利用手性双恶唑啉作为ECL进行对映体选择性[2，3]-Wittig重排的第一个例子。较少

项目成果

中井 武: "Wittig Rearrangement of α-(Propargyloxy)-alkyllithiums:Periselectivity and Steric Course at the Lithium-bearing Terminus" Synlett. 1045-1049 (1997)

Takeshi Nakai：“α-(丙炔氧基)-烷基锂的维蒂格重排：含锂末端的近选择性和空间过程”Synlett 1045-1049 (1997)。

中井 武: "Asymmetric[2,3]-Wittig rearrangement as a general tool for asymmetric synthesis" Pure and Appl.Chem.69. 595-600 (1997)

Takeshi Nakai：“不对称[2,3]-Wittig重排作为不对称合成的通用工具”Pure and Appl.Chem.69 (1997)。

中井 武: "Cyclization of Enantio-Enriched α-(Homoallyloxy)Alkyllithiums:Evidence for Retention of Configuration at The Carbanion Center" Tetrahedron Lett.38. 8939-8942 (1997)

Takeshi Nakai：“对映体富集 α-(Homoallyloxy)Alkyllithiums 的环化：碳负离子中心构型保留的证据”Tetrahedron Lett.38 (1997)。

Katsuhiko Tomooka, Hiroshi Yamamoto, Takeshi Nakai: "A Highly Stereocontrolled Conversion of O-Glycosides to C-Glycosides" J.Am.Chem.Soc.118. 3317-3319 (1996)

Katsuhiko Tomooka、Hiroshi Yamamoto、Takeshi Nakai：“O-糖苷到 C-糖苷的高度立体控制转化”J.Am.Chem.Soc.118。

Katsuhiko Tomooka, Takeshi Nakai: "[1,2] -Wittig rearrangement : Stereochemical features and synthetic utilities" J.Synth.Org.Chem.Jpn.54. 1000-1008 (1996)

Katsuhiko Tomooka、Takeshi Nakai：“[1,2]-Wittig 重排：立体化学特征和合成实用程序”J.Synth.Org.Chem.Jpn.54。