Development of Carbon-Carbon Bond Forming Reaction Utilizing New Mitsunobu Reagents

利用新型 Mitsunobu 试剂开发碳-碳键形成反应

• 批准号: 13672244
• 负责人: TSUNODA Tetsuto
• 金额: $ 1.98万
• 依托单位: Tokushima Bunri University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672244/
• 关键词: Mitsunobu reaction; Cyanomethylenetrimethylphosphorane (CMMP); Phosuphoranes; carbon-carbon bond formation; active methylene; 炭素-炭素結合合成

The Mitsunobu reaction, a popular alkylation reaction utilizing the redox system between diethylazodicarboxylate and triphenylphosphine, has a shortcoming that it can only be applied satisfactorily to nucleophile (HA) of pK_u less than 11. In order to overcome the limitation, we introduced several combinations of azodicarboxamides (TIPA, ADDP, TMAD, and DHTD) and tributylphosphine. In our continual search for new versatile reagents, we found cyanomethylenetrialkylphosphorane (CMBP, CMMP) was capable of mediating the alkylation of various HA of larger pK_u than 11.In our investigation, CMMP was found to be much more versatile in C-alkylation : it mediated the reaction of acids of pK_u【approximately equal】 23 (MT sulfone, benzyl phenyl sulfone, geranyl phenyl sulfone, etc.). Utilizing the C-alkylation reaction with these new reagents, we developed an efficient methodology for the synthesis of some biologically active compounds or their analogs, including pheromones, squalene synthetase inhibitors, and pyridine alkaloids.

Mitsunobu反应是利用二乙基偶氮二甲酸酯和三苯基膦之间的氧化还原体系进行的一种常用的烷基化反应，但其缺点是只适用于pK_u小于11的亲核试剂。为了克服这一局限性，我们引入了几种偶氮二甲酰胺(TIPA、ADDP、TMAD和DHTD)与三丁基膦的组合。在我们不断寻找新的多功能试剂的过程中，我们发现氰亚甲基三烷基膦(CMBP，CMMP)能够催化pK_u大于11的各种HA的烷基化反应。在我们的研究中，发现CMMP在C-烷基化反应中的用途更广泛：它介导了pK_u[大致相当]23的酸的反应。利用这些新试剂的C-烷基化反应，我们开发了一种有效的方法来合成一些生物活性化合物或其类似物，包括信息素、角鲨烯合成酶抑制剂和吡啶生物碱。

项目成果

T. Tsunoda, Eds. By The Society of Synthetic Organic Chemistry: "New Redox System for the Mitsunobu Reaction, My Favorite Organic Synthesis"Japan, Kagaku-Dojin Publishing Co., Inc. Tokyo. 232--233 (2002)

T.角田编辑。

Tetsuto Tsunoda: "My Favorite Organic Synthesis"The Society of Synthetic Organic Chemistry, Japan Kagaku-Dojin Publishing Co., Inc. Tokyo. 232-233 (2002)

Tetsuto Tsunoda：“我最喜欢的有机合成”合成有机化学学会，日本化学同人出版公司，东京。

I. Sakamoto, H. Kaku, and T. Tsunoda: "Preparation of (Cyanomethylene)trimethylphosphorane as a New Mitsunobu-Type Reagent"Chem. Pharm. Bull.. 51(4), in press. (2003)

I. Sakamoto、H. Kaku 和 T. Tsunoda：“作为新型 Mitsunobu 型试剂的（氰亚甲基）三甲基正膦的制备”Chem。

Kaori Uemoto: "Prenyl and geranyl phenyl sulfone, A new carbon nucleophile for Mitsunobu-type alkylation"Tetrahedron Lett.. 42.5. 905-907 (2001)

Kaori Uemoto：“异戊二烯基和香叶基苯砜，一种用于 Mitsunobu 型烷基化的新型碳亲核试剂”Tetrahedron Lett.. 42.5。

K.Uemoto, A.Kawahito, N.Matsushita, I.Sakamoto, H.Kaku, and T.Tsunoda: "Prenyl and geranyl phenyl sulfone, A new carbon nucleophile for Mitsunobu-type alkylation."Tetrahedron Lett.. 42(5). 905-907 (2001)

K.Uemoto、A.Kawahito、N.Matsushita、I.Sakamoto、H.Kaku 和 T.Tsunoda：“异戊二烯基和香叶基苯砜，用于 Mitsunobu 型烷基化的新型碳亲核试剂。”Tetrahedron Lett.. 42(5