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反应是一种流行的烷基化反应，利用偶氮二甲酸二乙酯和三苯基膦之间的氧化还原体系，其缺点是只能令人满意地应用于pK_u小于11的亲核试剂（HA）。为了克服该限制，我们引入了几种组合偶氮二甲酰胺（TIPA、ADDP、TMAD 和 DHTD）和三丁基膦。通过不断寻找新的多功能试剂，我们发现氰基亚甲基三烷基正膦（CMBP、CMMP）能够介导 pK_u 大于 11 的各种 HA 的烷基化。在我们的研究中，发现 CMMP 在 C-烷基化中具有更多用途：它介导pK_u【约等于】23的酸的反应（MT砜、苄基苯砜、利用这些新试剂的C-烷基化反应，我们开发了一种有效的合成一些生物活性化合物或其类似物的方法，包括信息素、角鲨烯合成酶抑制剂和吡啶生物碱。

项目成果

Izumi Sakamoto: "Preparation of (Cyanomethylene)trimerhylphosphorane as a New Mitsunobu-Type Reagent"Chemical & Pharmaceutical Bulletin. 51・4. (2003)

坂本泉：“作为新型光延型试剂的(氰基亚甲基)三甲基正膦的制备”化学与制药通报51・4。

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。

Sho Ito: "New Mitsunobu Reagents in C-C Bond Formation. Application to Natural Product Synthesis"Pure & Appl.Chem.. 71・6. 1053-1057 (1999)

伊藤翔：“C-C键形成中的新Mitsunobu试剂。在天然产物合成中的应用”Pure & Appl.Chem. 71・6（1999）

Izumi Sakamoto: "Preparation of (Cyanomethylene) trimethylphosphorane as a New Mitsunobu-Type Reagent"Chemical & Pharmaceutical Bulletin. 51・4(In press). (2003)

坂本泉：“作为新型光信型试剂的（氰基亚甲基）三甲基正膦的制备”《化学与制药通报》51・4（出版中）。