Enantioselective N-heterocyclic carbene-catalysed intermolecular crossed benzoin condensations: improved catalyst design and the role of in situ racemisation.

The enantioselective intermolecular crossed-benzoin condensation mediated by novel chiral N-heterocyclic carbenes derived from pyroglutamic acid has been investigated. A small library of chiral triazolium ions were synthesised. Each possessed a tertiary alcohol H-bond donor and a variable N-aryl substituent. It was found that increasing both the steric requirement and the electron-withdrawing characteristics of the N-aryl ring led to more chemoselective, efficient and enantioselective chemistry, however both quenching the reaction at different times and deuterium incorporation experiments involving the product revealed that this is complicated by product racemisation in situ (except in the case of benzoin itself), which explains the dependence of enantioselectivity on the electrophilicity of the reacting aldehydes common in the literature. Subsequent protocol optimisation, where one reacting partner was an o-substituted benzaldehyde, allowed a range of crossed-benzoins to be synthesised in moderate-good yields with moderate to excellent enantioselectivity.

Revisiting the Perfluorinated Trityl Cation.

Although ultimately not isolable for X-ray structural characterization, the free perfluorinated trityl cation was shown to be observable in neat triflic acid, which represents milder conditions than previous reports of this cation in "magic acid" or oleum. A triflate-bound species could be generated in organic solvents using stoichiometric amounts of triflic acid and was shown to be synthetically viable for hydride abstraction from Et3 SiH. It was demonstrated that the para-position on the -C6 F5 rings is the primary point of attack for decomposition of the cation.

Highly chemoselective intermolecular cross-benzoin reactions using an ad hoc designed novel N-heterocyclic carbene catalyst.

The design of a novel N-heterocyclic carbene catalyst incorporating a bulky yet highly electron-deficient N-aryl substituent has allowed the development of an efficient protocol for the first highly chemoselective intermolecular benzoin condensations between two non-identical aromatic aldehydes.

Aerobic oxidation of NHC-catalysed aldehyde esterifications with alcohols: benzoin, not the Breslow intermediate, undergoes oxidation.

Benzoin (and neither the Breslow intermediate nor the NHC-aldehyde tetrahedral adduct) has been unambiguously identified as the oxidised species in aerobic NHC-catalysed aldehyde esterifications.

NHC-catalysed aerobic aldehyde-esterifications with alcohols: no additives or cocatalysts required.

A highly efficient, broad scope, additive-free mild protocol for the oxidative carbene-catalysed esterification of aldehydes (including the related aqueous oxidation to acids) has been developed.