Kinetic and structure-activity studies of the triazolium ion-catalysed benzoin condensation.

Steady-state kinetic and structure-activity studies of a series of six triazolium-ion pre-catalysts 2a-2f were investigated for the benzoin condensation. These data provide quantitative insight into the role of triazolium N-aryl substitution under synthetically relevant catalytic conditions in a polar solvent environment. Kinetic behaviour was significantly different to that previously reported for a related thiazolium-ion pre-catalyst 1, with the observed levelling of initial rate constants to νmax at high aldehyde concentrations for all triazolium catalysts. Values for νmax for 2a-2f increase with electron withdrawing N-aryl substituents, in agreement with reported optimal synthetic outcomes under catalytic conditions, and vary by 75-fold across the series. The levelling of rate constants supports a change in rate-limiting step and evidence supports the assignment of the Breslow-intermediate forming step to the plateau region. Correlation of νmax reaction data yielded a positive Hammett ρ-value (ρ = +1.66) supporting the build up of electron density adjacent to the triazolium N-Ar in the rate-limiting step favoured by electron withdrawing N-aryl substituents. At lower concentrations of aldehyde, both Breslow-intermediate and benzoin formation are partially rate-limiting.

A Mechanistically and Operationally Simple Route to Metal-N-Heterocyclic Carbene (NHC) Complexes.

We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal-N-heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base-assisted concerted process that does not require free NHC formation. The synthetic protocol was found applicable to a number of transition-metal- and main-group-centered NHC compounds and could become the synthetic route of choice to form M-NHC bonds.

Rate and equilibrium constants for the addition of N-heterocyclic carbenes into benzaldehydes: a remarkable 2-substituent effect.

Rate and equilibrium constants for the reaction between N-aryl triazolium N-heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3-(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2-substituent in these reactions and provide insight into the chemoselectivity of cross-benzoin reactions.

Rate and Equilibrium Constants for the Addition of N-Heterocyclic Carbenes into Benzaldehydes: A Remarkable 2-Substituent Effect.

Rate and equilibrium constants for the reaction between N-aryl triazolium N-heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3-(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2-substituent in these reactions and provide insight into the chemoselectivity of cross-benzoin reactions.

Stereospecific asymmetric N-heterocyclic carbene (NHC)-catalyzed redox synthesis of trifluoromethyl dihydropyranones and mechanistic insights.

N-heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels-Alder reactions of α-aroyloxyaldehydes with ß-trifluoromethyl enones generates synthetically useful dihydropyranones containing a stereogenic trifluoromethyl substituent in good yields (up to 81%) and excellent diastereoselectivity and enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific, with use of either (E)- or (Z)-ß-trifluoromethyl enones forming syn- or anti-dihydropyranone products, respectively. Mechanistic studies through in situ kinetic analysis of the reaction reveal key differences in reactivity between chiral NHC precursor 1 and an achiral NHC precursor.

Proton transfer reactions of triazol-3-ylidenes: kinetic acidities and carbon acid pKa values for twenty triazolium salts in aqueous solution.

Second-order rate constants have been determined for deuteroxide ion-catalyzed exchange of the C(3)-proton for deuterium, k(DO) (M(-1) s(-1)), of a series of 20 triazolium salts in aqueous solution at 25 °C and ionic strength I = 1.0 (KCl). Evidence is presented that the rate constant for the reverse protonation of the triazol-3-ylidenes by solvent water is close to that for dielectric relaxation of solvent (10(11) s(-1)). These data enabled the calculation of carbon acid pK(a) values in the range 16.5-18.5 for the 20 triazolium salts. pD rate profiles for deuterium exchange of the triazolium salts reveal that protonation at nitrogen to give dicationic triazolium species occurs under acidic conditions, with estimates of pK(a)(N1) = -0.2 to 0.5.

Organic base effects in NHC promoted O- to C-carboxyl transfer; chemoselectivity profiles, mechanistic studies and domino catalysis.

The O- to C-carboxyl transfer of oxazolyl carbonates promoted by triazolinylidenes, generated in situ with NEt(3), shows a markedly different rate and chemoselectivity profile to the same reaction promoted by triazolinylidenes generated using KHMDS. The mechanism of these pathways has been probed through extensive crossover studies to understand this process. The use of NEt(3) as a base allows domino multi-step reaction sequences to be developed, although chiral NHCs only generate modest levels of asymmetric induction (<15% ee) in these domino reaction processes.