Azines direct ring metallation

In the last year, a lot of attention has been paid to the efficient directing effects of 2-pyridyl groups to facilitate a number of useful synthetic transformations. Mongin and co-workers have examined 2-pyridyl groups to direct metalation of 2-phenylpyridines 37 <04JOC6766>. Under the kinetic conditions studied no nucleophilic addition to the azine ring was observed. Lithiation occurred cleanly at the 2 -position of the benzene ring, as shown in Scheme 16, to yield compounds 38. 

Since the positions of the Is,min are the locations, on the average, of the most easily removed electrons, these should also be the sites that are most reactive toward electrophilic attack. This has been fully confirmed for a group of monosubstituted benzene derivatives [10,21]. The Is,min correctly predict the ortho/para- or meta- directing tendencies of the substituents, even the rather unusual NH3+, which is a metal para director [22]. Furthermore, the magnitudes of the Is,min relative to that of unsubstituted benzene correctly indicate whether each substituent activates or deactivates the aromatic ring toward electrophiles. These analyses have been extended to other aromatic systems, including azines and azine N-oxides [18,23,24]. 

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