Synthesis and kinetic evaluation of triazolium salt organocatalysts: towards the d1-deuteration of aldehydes

Abstract

Triazolyl precursors to N-heterocyclic carbenes (NHCs) have been recognized as versatile organo-catalysts for synthetic modifications. Recently, a kinetic evaluation for benzoin condensation in the presence of NHC suggested a possible pathway towards the d1-deteration of aldehydes.

Overall, seven N-aryl substituted triazolium salts have been prepared, and six mechanistic studies of the triazol-3-ylidene-catalyzed benzoin condensation has been performed. In situ 1H NMR spectroscopic studies of the reaction in triethylamine-buffered methanol-d4 solution at 25 °C suggest the 3-hydroxyaryl adduct to be the only intermediate which can be observed. The formation of Breslow intermediate could be proved by the trace of adduct deuteration.

Equilibrium constants, K1, M-1, for hydroxyaryl adduct formation were determined from the reaction of triazolium catalyst with aldehyde, clearly suggest the ortho-substituents on the N-aryl group of both catalysts and aldehydes increase K1. Our results suggest the dramatically decrease (1.2-fold) in K1 for the reaction of benzaldehyde in the order of increasing steric hindrance of aryl-substituents of catalysts (N-mesityl to N-triisopropyl). By contrast, the reaction of 2-methoxybenzaldehyde do shows the increases of K1 in the order N-phenyl (118) < N-mesityl (524) < N-triisopropyl (1738), which is caused by the larger variables in the decomposition rate constant of adduct, k-1 (s-1), than formation, k1 (M-1s-1). In order of the increased steric hindrance, k1 shows the values of N-phenyl (3.44 × 10-2) > N-mesityl (2.45 × 10-2) > N-isorpopyl (1.91 × 10-2), and k-1 of N-phenyl (2.92 × 10-4) > N-mesityl (4.67 × 10-5) > N-isorpopyl (1.10 × 10-5).

The trace of H/D-exchange of aldehyde at d1 position was evaluated under same condition. The further reaction of Breslow intermediate to benzoin, deuterated adduct and deuterated aldehyde was only observed for the reaction of benzaldehyde with N-mesityl and triisopropyl catalysts. 48 hours reaction suggest the slightly higher deuterium incorporation into adduct/aldehyde for N-mesityl than triisopropyl. For the reaction 2-methoxybenzaldehyde with N-mesityl and triisopropyl catalysts, the sluggish onwards reaction of adducts prevent the quantitative assessment, although we expect larger variations of reaction parameters. The highly reactive N-pentafluorophenyl triazolium catalyst breaks the threshold of benzoin product formation for 2-methoxybenzaldehyde, however, also results in the fast consumption of aldehyde to adduct. The rapid formation of deuterated adduct and deuterated benzoin product suggest the formation of d1-deuterated aldehyde while with extremely fast decay.

Finally, X-ray crystallography suggested the formation of a novel NHC adduct of N-pentafluorophenyl triazolium salts.