Stereoselective Carbon-carbon Bond Forming Reactions Using Chiral Environment Designed from Carbohydrates

利用碳水化合物设计的手性环境进行立体选择性碳-碳键形成反应

• 批准号: 09650965
• 负责人: TADANO Kin-ichi
• 金额: $ 2.11万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09650965/
• 关键词: Carbohydrates; Chiral Environment; Chiral Auxiliary; Asymmetric Synthesis; 1,4-Conjugate Additions; Radical Additions; Diels-Alder reactions; ディールス-アルダー反応; β(ベータ)位置換ブタン酸; 環状糖質構造; 不斉誘導; 分子内アルドール反応; 1、4-共役付加反応

The following subjects were explored for verification of the effectiveness of hexofuranoses and hexopyranoses as stereocontroller for diastereoselective carbon-carbon bond forming reactions.1. The orthoester Claisen rearrangement of (Z)-3-deoxy-3-C-[(hydroxymethyl)methylene]-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranose with 1,1-dimethoxycyclohexane provided a 3.3:1 diasteromeric mixture of the rearrangement products. The Claisen rearrangement with 3,3-dimethoxycyclohexene provided a single product. Hydride additions and 1,4-conjugate additions for these rearrangement products were investigated, and some of the additions proceeded highly stereoselectively.2. The conjugate additions of a variety of organocopper reagents or dimethyl malonate anion to a spirocyclic cyclopent-2-enone connecting a 1,2:5,6-di-O-isopropylidene-α-D-glucofuranosyl ring as a constituent of the spirocyclic structure proceeded stereoselectively affording a variety of β-functionalized cyclopentanone derivatives … More . In addition, the thermal treatment of (1S,3R,4R,5S)-7-(hydroxymethyl)-3,4-(isopropylidenedioxy)1-[(1R)-1.2-(isopropylidenedioxy)ethyl]-2-oxaspiro[4.4]non-6-ene with triethyl orthoacetate afforded the Claisen rearrangement product with a high level of diastereoselectivity.3. The 1,4-conjugate additions of a variety of organocopper reagents to some 4-O-crotonyl derivatives of methyl α-D-glucopyranoside proceeded with exceptionally high levels of diastereochemical induction to provide the adducts carrying a β-vinylated (or alkylated) butanoic ester at the C-4 carbon atom. The 1,4-conjugate additions to a 6-O-crotonyl derivative aforded the adduct incorporating reverse configuration at the β-carbon to that obtained from the 4-O-crotonyl derivatives. Removal of the carbohydrate template from each adduct provided β-vinylated (or alkylated) butanoic acid in enantiopure or highly-enriched form. The conjugate addition of alkyl radicals to the above mentioned 4-O-crotonyl derivative proceeded with high stereoselectivity. The D-galactose-derived and D-mannose-derived 2-O-, 3-O-crotonyl esters also served as good stereocontrollers for 1,4-conjugate addition reactions and Diels-Alder reactions. Less

为了验证六氟脲糖和六吡喃糖作为非对映选择性碳-碳键形成反应的立体控制器的有效性，我们进行了以下实验。(Z)-3-脱氧-3- c -[（羟甲基）亚甲基]-1,2:5,6-二- o-异丙基-α- d -核糖-己糖与1,1-二甲氧基环己烷的正构酯Claisen重排得到了3.3:1的非对映体混合物。与3,3-二甲氧基环己烯的Claisen重排提供了一个单一的产物。对这些重排产物的氢化物加成和1,4-共轭加成进行了研究，其中一些加成进行了高度的立体选择性。将多种有机铜试剂或丙二酸二甲酯阴离子与螺环环戊-2-烯酮偶联加成，连接1,2:5,6-二- o -异丙基-α- d -葡萄糖脲基环，作为螺环结构的组成部分，进行立体选择性地产生各种β功能化的环戊酮衍生物。此外，(1S,3R,4R,5S)-7-（羟甲基）-3,4-（异丙基二氧基）1-[(1R)-1.2-（异丙基二氧基）乙基]-2- oxspio[4.4]非6-烯与正乙酸三乙酯热处理，得到了具有高非对映选择性的Claisen重排产物。在一些甲基α- d -葡萄糖吡喃苷的4-O-crotonyl衍生物上，各种有机铜试剂的1,4-共轭加成进行了异常高水平的非对映化学诱导，以提供在C-4碳原子上携带β-乙烯化（或烷基化）丁酸酯的加合物。6- o -巴豆基衍生物的1,4共轭加成使其在β-碳上的构型与4- o -巴豆基衍生物的构型相反。从每个加合物中去除碳水化合物模板，以对映纯或高富集形式提供β-乙烯化（或烷基化）丁酸。烷基自由基与上述4- o -巴豆基衍生物的共轭加成具有很高的立体选择性。d -半乳糖衍生和d -甘露糖衍生的2-O， 3- o -巴豆基酯也可作为1,4共轭加成反应和diols - alder反应的良好立体控制器。少

项目成果

戸谷希一郎(Kiichiro Totani): "Highly Stereoselective 1,4-Conjugate Addition of Organocopper Reagents to Methyl α-D-Glucopyranoside derivatives Tethering an Unsaturated Ester Moiety at C-4 or C-6"Organic Letters. 1(9). 1447-1450 (1999)

Kiichiro Totani：“有机铜试剂与甲基 α-D-吡喃葡萄糖苷衍生物的高度立体选择性加成，在 C-4 或 C-6 处束缚不饱和酯部分”有机快报 1(9)。 ）

高尾賢一他3名: "Stereoselective Carbon-carbon Bond Forming Reactions of Chiral Cyclopen-2-enone and Cyclopenete-1-methanol, Both Spiro-connecting a 1,2:5,6-di-O-isopropylidene-α-D-glucofuranosyl Ring"Tetrahedron: Asymmetry. 11. 453-464 (2000)

Kenichi Takao 和其他 3 人：“手性环戊二烯酮和环戊二烯-1-甲醇的立体选择性碳-碳键形成反应，两者均螺接 1,2:5,6-二-O-异亚丙基-α-D -呋喃葡萄糖基环”四面体：不对称性。11. 453-464 (2000)

村田毅他6名: "A Chiral Cyclohex-2-enone carrying a Hexofuranosyl Substituent Which Directs Highly Stereoselective 1,4-Congugate Additions"Tetrahedron: Asymmetry. 9. 4203-4217 (1998)

Takeshi Murata 和其他 6 人：“携带六呋喃糖基取代基的手性环己酮，可直接进行高度立体选择性 1,4-共轭加成”四面体：不对称性 9. 4203-4217 (1998)。

戸谷希一郎他4名: "Highly Stereoselective 1,4-Conjugate Addition of Organocopper Reagents to Methyl α-D-Glucopyranoside derivatives Tethering an Unsaturated Eater Moiety at C-4 or C-6"Organic Letters. 1. 1447-1450 (1999)

Kiichiro Toya 和其他 4 人：“有机铜试剂与甲基 α-D-吡喃葡萄糖苷衍生物的高度立体选择性 1,4-共轭加成，在 C-4 或 C-6 处束缚不饱和的吞噬部分”有机快报 1. 1447-1450 (1999) ）

Ken-ichi Takao, Hiroshi Saegusa, Gohshi Watanabe and Kin-ichi Tadano: "Stereoselective Carbon-carbon Bond Forming Reactions of Chrial Cyclopen-2-enone and Cyclopenete-1-methanol, Both Spiro-connecting a 1,2: 5,6-di-O-isopropylidene-α-D-glucofuranosyl Ring

Ken-ichi Takao、Hiroshi Saegusa、Gohshi Watanabe 和 Kin-ichi Tadano：“Chrial Cyclopen-2-enone 和 Cycopenete-1-methanol 的立体选择性碳-碳键形成反应，两者均通过螺环连接 1,2: 5,6 -二-O-异亚丙基-α-D-呋喃葡萄糖基环