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

Mitsunobu反应是一种常用的利用二乙基二羧酸盐和三苯基膦氧化还原体系的烷基化反应，它的缺点是只能满意地应用于pK_u小于11的亲核试剂（HA）。为了克服这一限制，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cyanomethylenetrialkylphospane （CMBP， CMMP）能够介导各种pK_u大于11的HA的烷基化反应。在我们的研究中，CMMP被发现在c -烷基化中具有更广泛的用途：它介导pK_u【近似等于】23的酸（MT砜，苄基苯基砜，香叶基苯基砜等）的反应。利用这些新试剂的c -烷基化反应，我们开发了一种高效的方法来合成一些生物活性化合物或它们的类似物，包括信息素、角鲨烯合成酶抑制剂和吡啶生物碱。

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.