The zinc complex catalyzed hydration of alkyl isothiocyanates

Based upon our preceding studies of the hydration of CO 2 , COS and CS 2 , accelerated by the carbonic anhydrase (CA) using simplified [ZnL 3 OH] + complexes as model catalysts, we calculated the hydration mechanisms of both the uncatalyzed and the [ZnL 3 OH] + -catalyzed reactions (L = NH 3 ) of isothiocyanates RNCS on the B3LYP/6-311+G(d,p) level of theory. Interestingly, the transition state for the favored metal mediated reaction with the lowest Gibbs free energy is only slightly higher than in the case of CO 2 (depending on the attacking atom (N or S). Calculations under inclusion of solvent corrections show a reduction of the selectivity and a slight decrease of the Gibbs free energy in the rate-determining steps. The most plausible pathway prefers the mechanism via a Lindskog proton-shift transition state leading to the thermodynamically most stable product, the carbamatic-S-acid. Furthermore, powerful electron withdrawing substituents R of the cumulenic substrates influence the selectivity of the reaction to a significant extent. Especially the CF 3 -group in trifluoromethylisothiocyanate reverses the selectivity. This investigation demonstrates that reaction principles developed by nature can be translated to develop efficient catalytic methods, in this case presumably for the transformation of a wide variety of heterocumulenes aside from CO 2 , COS and CS 2 . Figure Competing transition structures for the [ZnL 3 OH] + -mediated activation of isothiocyanates