Synthetic Studies in the 5-Thio-D-xylopyranose Series. Part 1. A Ready Access to C-Hetaryl 5-Thio-D-xylopyranosides by Electrophilic Substitution.

Abstract Reaction of O -(2,3,4-tri- O -acetyl-5-thio- α -D-xylopyranosyl) trichloroacetimidate 3 with heterocyclic compounds such as furan, thiophene and benzothiophene in the presence of boron trifluoride etherate at −78 °C for ∼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- α -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-α-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.