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

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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.