THE REGIOSPECIFIC C-3 LITHIATION OF 5-ETHYL-2-FUROIC ACID - AN APPROACH TO KEY NATURAL PRODUCT INTERMEDIATES

Treatment of 5-ethyl-2-furoic acid with n-butyl-lithium in tetrahydrof uran gave regiospecific C-3 lithiation, whereas treatment of the same acid with lithium di-isopropylamide (LDA) afforded only starting mater ial. The synthetic utility of di-lithiated 5-ethyl-2-furoic acid has b een demonstrated with the synthesis of two substituted 3-benzyl-5-ethy l-2-furoic acid derivatives which are key intermediates for the prepar ation of naturally occurring cytotoxic 2-ethylfuronaphthoquinones. Rea ction of the C-3 lithiated species with two equivalents of benzaldehyd e and subsequent reduction afforded the corresponding 3-benzyl-5-ethyl -2-furoic acids. An alternative route to 5-ethyl-2-furoic acid has bee n described allowing for a more convenient preparation of longer-chain 5-alkyl-2-furoic acids.