Reactions of C-metallated Diazines

Typically, lithium tetramethylpiperidide has been used for the kinetically-controlled metallation of substituted diazines in some cases the use of a somewhat higher temperature allows equilibration to a thermodynamic anion. 

Lithiopyrimidines, -pyrazines, and -pyridazines have been converted by exchange with zinc chloride into the more stable zinc compounds for use in palladium-catalysed couplings (section 11.5.2). Magnesium derivatives have been prepared by reaction of 5-bromopyrimidines with n-butylmagnesium bromide and cerium compounds (which give better results than lithiopyrimidines in reactions with enolisable ketones) can be prepared from either bromo- or lithiopyrimidine.  

Palladium- (and nickel-) -catalysed coupling reactions proceed normally on halodiazines and the equivalent triflates, the most significant feature being the enhanced reactivity relative to chlorobenzenes of chlorine at position a and 7 to a nitrogen, just as in pyridine chemistry. In some particularly activated caes, this extra activation is sufficient to overcome the normally higher reactivity of bromine, but not 

Palladium- (and nickel-) catalysed coupling reactions proceed normally on halo-diazines, the most significant feature, as with pyridines, being the enhanced reactivity, relative to chlorobenzene, of chlorine at positions a and y to a nitrogen, but it is important to recognise that this activation does not overcome the higher intrinsic reactivity of bromine and iodine at any position.  

In diazine chemistry, tin derivatives have normally been used for coupling reactions and have the particular advantage that they can be prepared without the use of organolithium intermediates. Boronic acids have been used occasionally, but as a general rule they are difficult to prepare at positions a to azine nitrogens - a major disadvantage in diazine chemistry. 

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