Rates of competing fluoride elimination and iodination from a thiamin-derived Breslow intermediate.

Rates of fluoride elimination and iodination of the Breslow intermediate (BI) derived from 2-(1-hydroxy-2,2,2-trifluoroethyl)-thiamin provide a quantitative assessment of competing reactions at C2α of the BI. The competition probes the intrinsic reactivity of this important class of intermediates. Fluoride elimination, which occurs upon formation of the BI, produces 2-(2',2'-difluoroacetyl)-thiamin, while the rate of iodination of the same BI provides a basis for estimating the rate of the competing protonation. The results provide rates for reactions of the BI, the Brønsted β for its formation by deprotonation, and the pK_A of the conjugate acid of the BI at C2α. Comparison with reactions of 3-fluoropyruvate with enzymes that promote the decarboxylation of pyruvate (via the adduct of thiamin diphosphate) indicates that spontaneous fluoride elimination (k_el = 7.5 ± 0.3 s^-1) from the enzymic BI has a lower barrier than the reaction pathway that is normally promoted by the enzymes.