A general synthesis of 2- or 3-alkyl substituted 5-hydroxymethyl-#delta#-valerolactones, precursors of 5-formyl-#delta#-valerolactones, via lithiated N-allyl(bisdimethylamino)-N-methylphosphoramide carbanions

摘要

A convenient strategy is reported for the synthesis of 2- or 3-alkylsubstituted 5-hydroxymethyl and 5-formyl-#delta#-valerolactones, which are very useful starting blocks for the total synthesis of leukotrienes and lactonic pheromones. It has been found that lithiated enephosphoramide ambident anions reacted exclusively in the #gamma# position with 2,3-O-isopropylidene glycerol triflate to give corresponding alkylated enephosphoramides by a C3-C3 backbone connection. Enephosphoramide group was further selectively hydrolyzed in the presence of isopropylidene function in mild acidic conditions and led to expected aldehydes in high yields. Oxidation of these aldehydes using silver oxide or potassium permanganate afforded corresponding acids. Further hydrolysis of the isopropylidene group led to unstable dihydroxyacids which directly lactonized. The latter were converted to 5-formyl-#delta#-valerolactones using PDC oxidant.