Pergamon Tetrahedron Letters, Vol. 38, No. 34, pp. 6079-6082, 1997 © 1997 Elsevier Science Ltd All rights reserved. Printed in Great Britain PII: S0040-4039(97)01372-5 0o40-4039/97 $t7.0o + 0.00 Studies Towards Total Synthesis of Borrelidin, Regioselective Methylation of Bis- epoxides and Structure Determination Nizar Haddad*, Ashraf Brik and Michael Grishko Department of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel. Abstract: Regioselective methylation ofbis-epoxides 9 were examined. Two examples of high regioselectivity and yield were achieved. Structure determination of the four possible regioisomers provide useful information for structure determination of structurally related flexible molecules. © 1997Elsevier ScienceLtd. As part of our studies towards a total synthesis ofborrelidin (1), and interest in studying the relation between relative configuration of polysubstituted alkanes and the conformational distribution of such "flexible molecules with defined shape", 1 we have developed a versatile and highly stereoselective approach for the synthesis of (2) (C2-Ct 2 segment of borrelidin) and related isomers. 2 The synthesis based on enantioselective preparation of bis-epoxide 3 ( >99.2 %ee, 29% total yield of five steps starting from meso-diol 4), followed by regioselective methylation of the bis-epoxide. 2 Regioselective alkylation ofthreo-epoxides, derived from Eoallylic alcohols, that produce 1,2-diols, is a well documented reaction3. However, the regioselectivity and yields of these reactions could be strongly decreased 4 when applied in the alkylation of erythro-epoxy alcohols. Regioselective addition of methyl substituents to the bis-epoxide 3, structure determination of the four possible regioisomers and convenient method for the determination ofC 1 and C 1 ! positions in 2 and its related regioisomers are presented. OH CN Borrelidin 1 ~o OR 1 II, , ~ O R 3 °,,2 - R 2 C2-C12 segment R20 of borrelidin R20- , OR3 HO"~ A j~_ ~...~ .~ 'OH RO~'ORI~ ~,.~ T -~ ~,,,~ ~ef. 2 2 3 Scheme 1 .o o. 4 6079