Wadsworth-Emmons homologation

The final steps of the synthesis are summarized in Scheme 34. After a sequence of protection-reduction-oxydation, 171 was transformed to aldehyde 172 which was directly submitted to a Horner-Wadsworth-Emmons homologation with the requisite stabilized reagent K under Ando conditions [115] to give the corresponding a,(3-unsaturated ester 173 (Z/E > 95/5) in 84% yield. Treatment of ester 173 with 1% HC1, EtOH led to (-)-pironetin after purification (89% yield). 

The 1,3-propanediol ester, thus prepared, was transformed readily into 7-(3, 4 -methylenedioxyphenyl)-6 -heptenal, and the latter homologated by Wadsworth-Emmons reaction with the ylid of triethyl-4-phosphonocrotonate to afford ethyl 11-(3, 4 -methylenedioxyphenyl)-2E,4E, 0E undecatrienoate. The latter was simply transformed by conventional methodology into the corresponding i-butylamide, pipercide. 

A Wadsworth-Emmons type reaction of diethyl t-butoxy(cyano)methyl-phosphonate (1) has been used for the homologation of aldehydes and ketones to acids, esters, and amides (Scheme 2). Clearly, the method is limited to compounds which are reasonably stable to both heat and Lewis acids. In addition, ketonic precursors must have at least three a-protons. Inside these limits, good yields are obtained (57—88%). 

A protocol for the two-carbon homologation of esters (350) to o,jS-un-saturated esters (352) has been described by Jamison and Webb. Application of multireactor allowed to cany out three-operations procedure involving the ester (350) reduction, phosphonate (351) deprotonation, and the Homer-Wadsworth-Emmons olefination (Scheme 119). ... 

An efficient access to (Z)-/l-fluoroallyl alcohols (382), based on the two carbon homologation of aromatic aldehydes by the Horner-Wadsworth-Emmons reaction with 2-(diethoxyphosphoryl)-2-fluoro-ethanethioic acid S-ethyl ester (381), followed by reduction with sodium borohydride, has been devepoped by Rolando and co-workers (Scheme 134). ... 

---