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

Richard S Massey,Jiayun Zhu,Andrew D Smith,Jacob Murray,Christopher J Collett,Annmarie C O'Donoghue

doi:10.1039/d0ob02207a

Abstract

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.

Highlights

N-Heterocyclic carbenes (NHCs) have made a major impact on the field of catalysis and are arguably one of the most versatile, efficient classes of organocatalyst
Initial rate data for 2a–f were fit to a steady-state rate equation (eqn (2)), derived for the Breslow intermediate IV in Scheme 2, with the assumption that the concentration of adduct ([intermediate formation from (III)]) was equal to that of catalyst ([I]). This assumption is validated by our previous kinetic NMR studies with stoichiometric aryl aldehyde and triazolium salt concentrations in the same triethylamine-buffered methanol medium, which showed that adduct (III) forms rapidly and reversibly from these reactants at 25 °C.6b These previous studies for a range of aryl aldehydes and triazolium catalysts included the stoichiometric kinetic analysis of 2a–d and benzaldehyde, permitting access to rate and equilibrium constants for formation of (III).6b Half-lives (t1/2) for adduct III formation at 25 °C could be calculated as ∼670 s and ∼16 s for the lowest and highest [PhCHO]0, which would be predicted to be a minimum of ∼10fold lower again at 50 °C, and significantly smaller than the kinetic experiment measurement times employed in the initial rate analysis (ESI, section S4†)
In our previous stoichiometric studies involving 1 : 1 triazolium : aldehyde, which were followed to high % product, we investigated the contribution of the reverse reaction for the 2,4,6-trichlorophenyltriazolium tetrafluoroborate salt.6b Using two representative substituted benzoins as starting material,

Summary

Introduction

N-Heterocyclic carbenes (NHCs) have made a major impact on the field of catalysis and are arguably one of the most versatile, efficient classes of organocatalyst.

Results

Conclusion