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 O-(2,3,4-tri-O-acetyl-5-thio-alpha-D-xylopyranosyl) trichloroacetimidate 3 with heterocyclic compounds such as furan, thiophene and 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-xylopyranosyl bromide 4 led also to these previously unknown compounds, the yields being either comparable (furan) or lower (thiophene) due to 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 ring-restricted tetrahydrothiophene derivatives which were unambiguously assigned based on crystal analysis of the 3(S),4(S)-diacetoxy-2(R)-[bis-(2-furanyl)methyl]tetrahydrothiophene 8. Therefore, these model reactions shed light on possible routes to unprecedented C-hetaryl 5-thio-D-xylopyranosides by an electrophilic coupling, the selectivity of which being controlled by a proper tuning of the reaction parameters, in particular temperature and reaction time. Under kinetic conditions, C-hetaryl 5-thio-alpha-D-xylopyranosides can be formed predominantly, in particular from the bromide 4, on treatment with zinc chloride. Otherwise, anomerization occurred as well as ring-restriction to produce, particularly when using thiophene, more complex reaction mixtures. (C) 1998 Elsevier Science Ltd. All rights reserved.