Carbohydrate Reaction Intermediates: Effect of Ring-Oxygen Protonation on the Structure and Conformation of Aldofuranosyl Rings

The effect of ring-oxygen protonation on the structure and conformational properties of a model deoxyaldofuranose, 2-deoxy-β- d - glycero -tetrofuranose 2, has been examined with the use of NMR spectroscopy and ab initio molecular orbital calculations conducted at the HF/6-31G* level of theory. The computational method was validated by comparing the conformational behavior of 2 derived from PSEUROT treatment of 3 J HH values measured in 2 ( 2 H 2 O solvent) with that predicted from the theoretical calculations. Coupling data indicate that 2 favors S forms in solution (∼89% 4 T 3, ∼11% E 2 ), while MO data indicated more comparable populations of the same or very similar N and S forms. Protonation of 2 at the ring oxygen (O4), yielding 1, gave two distinct protonated forms which differed in the orientation of the proton about O4. Both forms showed substantial changes in ring structure and conformation compared to 2 . Protonated forms almost exclusively prefer S forms (E 3 ), and energy barriers for N/S interconversion were found to be considerably higher than those for 2, leading to the conclusion that 1 is more conformationally constrained than 2 . Bond lengths in the vicinity of O4 changed significantly upon conversion of 2 to 1; for example, the C1−O4 bond length increases by ∼14%, the C1−H1 and C1−O1 bond lengths decrease by 1−5%, and the C4−O4 bond length increases by ∼5%. These results indicate that O4 protonation predisposes 2 toward ring opening by inducing specific structural and conformational modifications, thus providing a more concise explanation of the role of acid catalysis in furanose anomerization ( i.e., 1 resembles the transition state of the acid-catalyzed anomerization reaction more than 2 ). The molecular orbital data obtained in this investigation also provide evidence for a new structural factor (a 1,3-effect involving oxygen lone-pair orbitals) that influences bond lengths in carbohydrates.