Development of New Versatile Reagents for Mitsunobu Reaction. -Utilization of Wittig Reagent as a New Mitsunobu Reagent-

光延反应新型多功能试剂的开发。

• 批准号: 09640653
• 负责人: TSUNODA Tetsuto
• 金额: $ 1.66万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09640653/
• 关键词: Mitsunobu reaction; Mitsunobu reagent; N,N,N', N'-Tetramethylazodicarboxamide (TMAD); 1,6-Dimethyl-1,5,7-hexahydro-1,4,6,7-tetrazocin-2,5-dione (DHTD); Cyanomethylenetributylphosphorane (CMBP); Cyanomethylenetrimethylphosphorane (CMMP); Phosuphorane

The Mitsunobu reaction, a popular alkylation reaction utilizing the redox system between diethyl azodicarboxylate and triphenylphosphine, has a shortcoming that it can only be applied satisfactorily to a nucleophile (HA) of PK_a 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_a than 11. Utilizing these reagents, the efficient alkylation of N-, C-, and O-nucleophiles, such as tosylamides, active methylene compounds, alcohols, and carboxylic acid was accomplished. The reaction was applied for the synthesis of biologically active compounds.

Mitsunobu反应是偶氮二甲酸二乙酯与三苯基膦之间的一种常用的氧化还原烷基化反应，但该反应仅适用于PK_a小于11的亲核试剂（HA）。为了克服这一缺点，我们引入了偶氮二甲酰胺（TIPA，ADDP，TMAD，DHTD）与三丁基膦的几种组合。在我们不断寻找新的通用试剂的过程中，我们发现氰基亚甲基三烷基正膦（CMBP，CMMP）能够介导PK_a大于11的各种HA的烷基化。利用这些试剂，实现了N-、C-和O-亲核试剂如甲苯磺酰胺、活性亚甲基化合物、醇和羧酸的有效烷基化。该反应被应用于生物活性化合物的合成。

项目成果

Tetsuto Tsunoda: "Mitsunobu-type Alkylation with Active Methine Compounds" Tetrahedron Letters. 37. 2459-2462 (1996)

Tetsuto Tsunoda：“活性次甲基化合物的 Mitsunobu 型烷基化”四面体字母。

Tetsuto Tsunoda: "Mitsunobu-type Alkylation of p-Toluenesulfonamide. A Convenient New Route to Primary and Secondary Amines." Tetrahedron Letters. 37. 2457-2458 (1996)

Tetsuto Tsunoda：“对甲苯磺酰胺的 Mitsunobu 型烷基化。一种便捷的伯胺和仲胺新路线。”

Tetsuto Tsunoda: "Formation of Heterocycles by the Mitsunobu Reaction.Stereoselective Sunthesis of (+)-α-Skytanthine." Tetrahedron Letters. 37. 2463-2466 (1996)

Tetsuto Tsunoda：“Mitsunobu 反应形成杂环。(+)-α-Skytanthine 的立体选择性合成。”37。2463-2466 (1996)

Tetsuto Tsunoda: "Mitsunobu Type C-N Bond Formation with 4,7-Dimethyl-3,5,7-hexahydro-1,2,4,7-tetrazocin-3,8-dione(DHTD),A New Cyclic Azodicarboxamide." Heterocycles. 47. 177-179 (1998)

Tetsuto Tsunoda：“与 4,7-二甲基-3,5,7-六氢-1,2,4,7-四唑星-3,8-二酮 (DHTD) 形成 Mitsunobu 型 C-N 键，一种新型环状偶氮二甲酰胺。”

T.Tsunoda, H.Yamamoto, K.Goda, and S.Ito: "Mitsunobu-type Alkylation of p-Toluenesulfonamide. A Convenient New Route to Primary and Secondary Amines." Tetrahedron Lett.37. 2457-2458 (1996)

T.Tsunoda、H.Yamamoto、K.Goda 和 S.Ito：“对甲苯磺酰胺的 Mitsunobu 型烷基化。一种便捷的伯胺和仲胺新路线。”