New Mitsunobu reagents in the C-C bond formation. Application to natural product synthesis

Abstract

Two types of new mediators were developed to replace DEAD-TPP in Mitsunobu reaction. One is N,N,N′ ,N′ -tetrasubstituted azodicarboxamide (e.g. TMAD or DHTD)-TBP system, and the other cyanomethylenetrialkylphosphoranes (e.g. CMBP and CMMP). While all of them are more effective than DEAD-TPP in the N- and C-alkylation with primary alcohols, DHTD and the phosphorane reagents are excellent mediators for the reaction with secondary alcohols. Furthermore, the phosphoranes, especially CMMP, were found to be much more versatile in C-alkylation: they mediate the reaction of acids of pKa ≅ 23 (MT sulfone, benzyl phenyl sulfone, geranyl phenyl sulfone, etc.). Utilizing the C-alkylation reaction with these new mediators, some natural products or their analogs, including pheromones and pyridine alkaloids, were synthesized. © 1999 IUPAC.