Still-Gennari modified HWE

The mechanism of the HWE olefination is not fully understood. In the Still-Gennari modified HWE olefination the phosphorous has two electron-withdrawing trifluoroalkoxy groups. In this case the rearrangement from the chelated adduct to form the oxaphosphetane is favored and the elimination step is faster than the initial addition which essentially becomes irreversible (unlike in the case of the regular HWE olefination). As a result the formation of the (Z)-stereoisomer is predominant. 

In C.J. Forsyth s total synthesis of phorboxazole A, the intramolecular version of the Still-Gennari modified HWE olefination was used to affect the macrocyclization of a complex it>/s(trifluoroethoxy) phosphonate-aldehyde precursor. The precursor was dissolved in toluene and was exposed to K2CO3 in the presence of 18-crown-6. The desired C1-C3 (Z)-acrylate moiety was formed in 77% yield with a 4 1 (Z ) ratio. Interestingly, when the same cyclization was carried out with the regular /)/s(dimethoxy) phosphonate, the macrocyclization was markedly slower, but the stereoselectivity was the same (4 1). 

Fig. 5 Still-Gennari modified HWE olefination for polyene synthesis...

---