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反应是利用偶氮二甲酸二乙酯和三苯基膦之间的氧化还原体系的一种流行的烷基化反应，其缺点是只能令人满意地应用于PK_a小于11的亲核试剂(HA)，为了克服该限制，我们引入了几种偶氮二甲酰胺（TIPA、ADDP、TMAD 和 DHTD）和三丁基膦的组合。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，可以实现 N-、C- 和 O-亲核试剂的有效烷基化，例如甲苯磺酰胺、活性亚甲基化合物、醇和羧酸。该反应用于生物活性化合物的合成。

项目成果

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。”

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 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: "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: "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：“Mitsunobu 型 C-N 键与 4,7-二甲基-3,5,7-六氢-1,2,4,7-tetrazocin-3,8-dione (DHTD) 形成，一种新的环状偶氮二甲酰胺”杂环。