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

A convenient strategy is reported for the synthesis of 2- or 3-alkylsubstit uted 5-hydroxymethyl and 5-formyl-delta-valerolactones, which are very usef ul starting blocks for the total synthesis of leukotrienes and lactonic phe romones, It has been found that lithiated enephosphoramide ambident anions reacted exclusively in the gamma position with 2,3-O-isopropylidene glycero l triflate to give corresponding alkylated enephosphoramides by a C3-C3 bac kbone connection. Enephosphoramide group was further selectively hydrolyzed in the presence of isopropylidene function in mild acidic conditions and l ed to expected aldehydes in high yields. Oxidation of these aldehydes using silver oxide or potassium permanganate afforded corresponding acids. Furth er hydrolysis of the isopropylidene group led to unstable dihydroxyacids wh ich directly lactonized. The latter were converted to 5-formyl-delta-valero lactones using PDC oxidant. (C) 1999 Elsevier Science S.A. All rights reser ved.