On the Organocatalytic Activity of N-Heterocyclic Carbenes: Role of Sulfur in Thiamine

摘要

The reaction energy profiles of the benzoin condensation from threenaldehydes catalyzed by imidazol-2-ylidene, triazol-3-ylidene, and thiazol-2-ylidene havenbeen investigated computationally. The barriers for all steps of all investigated reactionsnhave been found to be low enough to indicate the viability of the mechanism proposed bynBreslow in the 1950s. The most remarkable difference in the catalytic cycles has been thenincreased stability of the Breslow intermediate in case of thiazol-2-ylidene (by ca. 10 kcalmol) compared to the other two carbenes, which results in lower energy for the couplingnof the second aldehyde molecule, thus, increasing the reversibility of the reaction. Since thenanalogous transketolase reaction, being involved in the carbohydrate metabolism of manynorganisms, requires an initial decouplinga reverse benzoin condensationthisndifference provides a reasonable explanation for the presence of a thiazolium ring innthiamine instead of the otherwise generally more available imidazole derivatives. Then“resting intermediate” found by Berkessel and co-workers for a triazole-based catalyst wasnfound more stable than the Breslow intermediate for all of the systems investigated. Then(gas phase) proton affinities of several carbenes were compared, the relative trends being in agreement with the available (innaqueous solution) data. The hydrolytic ring-opening reaction of the thiazole-based carbene was shown to be different from thatnof imidazole-2-ylidenes.