STEREOCONTROL IN HORNER-WADSWORTH-EMMONS CONDENSATIONS OF ALPHA-PHOSPHONO LACTONES WITH ALDEHYDES - A SYNTHESIS OF INTEGERRINECIC ACID AND SENECIC ACID LACTONES

The Homer-Wadsworth-Emmons condensations of alpha-phosphono lactones were investigated under a variety of conditions. Upon treatment with KHMDS and 18-crown-6 in THF, condensations of the five-membered ring phosphono lactones 7a and 8 with propionaldehyde afforded the E olefins cleanly. In contrast, these phosphonates gave predominantly the Z olefins upon treatment with propionaldehyde, K2CO3, and 18-crown-6 in THF. A similar, though somewhat less-pronounced trend was observed with the six-membered ring phosphono lactone 9a. However, in its condensation with acetaldehyde the more functionalized phosphono lactone 4 gave the best E selectivity (ca. 9:1) when DBU/CH3CN was used, providing the methyl ester of integerrinecic acid lactone (5) in 77% isolated yield. When K2CO3/18-crown-6/toluene was employed in a parallel reaction, only slight selectivity for the Z isomer was observed, but the methyl ester of senecic acid lactone (6) still was obtained in 43-46% yield from the product mixture.