Conformational Analysis of Sulfur-Containing 6-Deoxy-l-hexose Derivatives by Molecular Modeling and NMR Spectroscopy. A Theoretical Study and Experimental Evidence of Intramolecular Nonbonded Interactions between Sulfur and Oxygen

6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-di-O-acetyl-2-S-phenyl-1,2-dithio-6-deoxy-β-l-glucopyranoside (9) and 3,4-di-O-acetyl-2,5-anhydro-6-deoxy-l-glucose diphenyldithioacetal (10) upon treatment with acetyl chloride, while 6-deoxy-l-mannose ethylenedithioacetal (3) yielded (4aR,6S,7S,8R,8aS)-7,8-diacetyloxy-6-methylhexahydro-4aH-[1,4]dithiino[2,3b]pyran (11), whose structure was further confirmed by X-ray diffraction, and
3,4-di-O-acetyl-2,5-anhydro-l-rhamnose ethylenedithioacetal (12). The geometry of the four rearranged products as well as that of 1-thio-6-deoxy-l-mannopyranosides 5 and 7 and their acetyl
derivatives 6 and 8 was studied by density functional theory (B3LYP/6-31G*) molecular models,
in combination with a Karplus-type analysis of the NMR vicinal coupling constants, revealing that
the six-membered ring of pyranosides 5−9 and 11 exists in a slightly distorted chair conformation
(6−13% distortion) and that the conformational behavior of the 2,5-anhydro-6-deoxy-l-glucose
dithioacetals 10 and 12 is strongly influenced by the presence of stabilizing intramolecular
nonbonded sulfur−oxygen 1,4- and 1,5-interactions. Compounds 9−12 were formed by a molecular
rearrangement via sulfonium ion intermediates followed by stereoselective intramolecular cyclizations as formulated by the quantum chemical calculations performed in the present study.