SYNTHETIC STUDIES IN THE 5-THIO-D-XYLOPYRANOSE SERIES PART-1 - A READY ACCESS TO C-HETARYL 5-THIO-D-XYLOPYRANOSIDES BY ELECTROPHILIC SUBSTITUTION

Reaction of -(2,3,4-tri-O-acetyl-5-thio-alpha-D-xylopyranosyl) trichlo roacetimidate 3 with heterocyclic compounds such as furan, thiophene a nd benzothiophene in the presence of boron trifluoride etherate at -78 degrees C for similar to 0.5 h leads to the corresponding C-hetaryl 5 -thio-D-xylopyranosides as anomeric mixtures obtained in 73, 79 and 64 % yield, respectively. Use of the 2,3,4-tri-O-acetyl-5-thio-alpha-D-x ylopyranosyl bromide 4 led also to these previously unknown compounds, the yields being either comparable (furan) or lower (thiophene) due t o the formation of tetrahydrothiophene derivatives. A mechanism based on the acid-catalyzed cleavage of the 2'-acetoxy group and/or a sulfur transannular participation is proposed to account for the observed ri ng-restricted tetrahydrothiophene derivatives which were unambiguously assigned based on crystal analysis of the xy-2(R)-[bis-(2-furanyl)met hyl]tetrahydrothiophene 8. Therefore, these model reactions shed light on possible routes to unprecedented C-hetaryl 5-thio-D-xylopyranoside s by an electrophilic coupling, the selectivity of which being control led by a proper tuning of the reaction parameters, in particular tempe rature and reaction time. Under kinetic conditions, C-hetaryl 5-thio-a lpha-D-xylopyranosides can be formed predominantly, in particular from the bromide 4, on treatment with zinc chloride. Otherwise, anomerizat ion occurred as well as ring-restriction to produce, particularly when using thiophene, more complex reaction mixtures. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.