Reactions of C-metallated 1,2-azoles

Complementarily, the lithiation of a SEM protected 2-phenylsulfonylimidazole takes place at C-4. Metal-halogen exchange of 4(5)-bromoimidazole is possible without protection.  

Although oxazoles follow the pattern and lithiate at C-2, 4-substituted products are produced with some electrophiles this is interpreted by a ring opening of the anion, to produce an enolate, which after C-electrophilic attack, recloses. An estimate by NMR spectroscopy showed the ring cleaved tautomer to dominate the equilibrium. The open enolates can be trapped by reaction with chlorotrimethylsi-lane the open, enol trimethylsilyl ether will undergo a thermal rearrangement to form a 2-trimethylsilyloxazole.  

The ring opening of oxazoles can be avoided by transmetallation, or by first forming a borane complex which is then lithiated as shown below.  

Oxazolylzinc compounds and oxazolyl tin compounds take part in coupling processes (see also below) without problems over ring opening. 

The palladium(0)-catalysed coupling of A-protected imidazoles has been extensively utilised, as illustrated by the examples below. The coupling of 4,5-diiodoimidazole protected with trimethylsilylethoxymethyl on A-1, was completely selective for the 5-halogen.  

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