Tetrahedron Letters, zyxwvutsrqponmlkjihgfedcbaZYX Vol. 35. No 20, pp. 3361-3364, 1994 Elsevier Science Ltd Printed in Great Britain 00&I-4039/94 S6.00+0.00 0040-4039(94)E05 17-2 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLK Tetrahydropyran Derivatives from p and &Hexonolactones Juan C. Bstevez,a Antony J. Fairbanks,B Kenneth Y. H&a Peter Wardb and George W. J. Flee@ aDyson Pert-ins Laboratory, oxford University, Oxford Centre for Molecular Sciences, South Parks Road, Oxford OX1 3QY, UK, bGlaxo Group Research, Greenford Road, Greenford, Middlesex UB6 OHE Abstract: Both 6- and y-hexonolactones provide templates for the construction of bicyclic la&ones in which a new tetrahydropyran ring has been formed from overall elimination of water from the C-2 and C-6 hydroxyl grou s. Such studies may provide a strategy for the synthesis of C-glycosides from elimination oP water between C-2 and C-6 of heptonolactones. Carbohydrate lactones have provided relatively short and efficient routes to a wide range of complex targets.1 including carbocycles2 and nitrogen hetcrocycles. 3 Reactions of protected a-triflates of y-&ones with potassium carbonate in methanol give oxetanes in good yields.4 whereas under the same conditions a- tritlates of &&tones afford excellent yields of tetrahydrofurans. 5 Treatment of both a-triflates of T- and 6 &tones with methanol under acidic conditions induces the formation of tetrahydrofurans, usually in very high yields.6 The formation of oxetanes and tctrahydrofurans involves overall loss of water between the hydroxyl groups at C-2 and either C-4 or C-5 of the &ones; the loss of water between C-2 and C-6 of a lactone would give rise to a new tetrahydtopyran synthesis and in the case of seven carbon lactones would provide a method for the formation of C-glycoside derivatives. This paper reports studies in which loss of water from &lactones such as 1 and y-lactones such as 4 gives bicyclic lactones 2 and 5, which by subsequent ring opening reactions may be converted to the tetrahydropyrtm derivatives 3 and 6, respectively. Zb; -++o-t_...~~e 4 5 s The isopropylidene la7 and cyclohexylidene zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGF lb* Glactones [Scheme I] can be directly dehydrated to the bicyclic &tones 2a m.p. 190-192 Oc. [a]~*~ -46.0 (c, 0.88 in CHC13)a*tc and 2b** m-p. 204-205 Oc, [a]B20 -43.8 (c, 1.1 in CHC13) under Mitsunobu conditions [triphenylphosphine and diethyl axodicarboxylate in tetrahydrofuran] in yields of 60% and 69% respectively. The structure of the bicyclic lactones 2 were confirmed by the reduction of 2b by lithium borohydride in tetrahydrofuran to give the ketal 8b oil, [a]~20 +2 1.9 (c, 1.13 in CHC13), [93% yield]; removal of the cyclohexylidene protecting group in 8b 3361