114 1,2-Azoles and 1,3-Azoles
Highly hindered analogues of these products, which have become known as ‘N-heterocyclic carbenes’ (NHCs), are
important ligands for transition metals, especially in catalytic processes. Isolable, crystalline carbenes can be derived,
via C-2-H deprotonation, even from a salt as simple as 1,3,4,5-tetramethylimidazolium. The NHC that has been most
utilized, in stabilizing both high and low valency states of metals, is the 1,3-bis(2,4,6-trimethylphenyl)-substituted imi-
dazole carbene (1,3-dimesitylimidazol-2-ylidene, usually represented as IMes). The pKaH values for NHCs, in the range
of 22–24, show them to be amongst the most basic, non-ionic compounds; they are strongly nucleophilic.
NHC–metal complexes for catalysis are usually generated in situ from the imidazolium salt and a base, but can be
prepared separately.
Reductions
There is little to say about oxidative manipulations of azoles, however there are some signifi cant reductive processes.
The N-O bond of isoxazoles, or isoxazolones is, like all N-O bonds, subject to hydrogenolysis over a noble metal
catalyst; this reveals 1,3-difunctionalised compounds that can fi nd various uses, not the least, in the synthesis of other
heterocyclic compounds.
A thiazolium ring can be fully reduced (without hydrogenolysis of sulfur) using a hydride reagent. This is central to a
general route for the synthesis of 2-hydroxyaldehydes, which is illustrated below.
Pericyclic reactions
Cycloaddition reactions of azoles as 4 components are important only for the 1,3-azoles, and amongst these, oxazole
reactions have been the most studied, for example reactions with alkynes, benzyne, singlet oxygen and with typical
alkene dienophiles are known. One use that can be made of alkyne adducts is to carry out the reaction at such a tem-
perature that a subsequent retro-Diels–Alder loss of a nitrile produces a furan.