Heteroaromatic directed ortho metalation

Victor Snieckus is well known for having developed powerful methodological tools for the synthesis of polysubstituted aromatics, in particular heteroaromatic directed ortho-metalation. Thus, in his chapter (No. 10), prepared with his co-author Christian Hartung, directed ortho-metalation is taken as a starting point for new synthetic aromatic chemistry. 

Heteroaromatic Directed ortho Metalation (HetDoM) in synthetic methodology ... 

Anctil, E. J. G., Snieckus, V. The directed ortho metalation-cross coupling symbiosis. Regioselective methodologies for biaryls and heterobiaryls. Deployment in aromatic and heteroaromatic natural product synthesis. J. Organomet. Chem. 2002, 653,150-160. 

The nucleophilicity of an organocobalt(III) species was utilized by Hummel and Ellman to achieve condensation of an azobenzene and an aldehyde to afford an A/ -aryl-2//-indazole derivative (Scheme 10.13) [35]. A combination of a cationic Cp Co complex bearing a noncoordinating B(CgF5)4 anion and acetic acid promotes direct addition of the azobenzene to the aldehyde through azo-directed ortho-metalation and subsequent insertion of the C=0 bond into the aryl-Co bond. While these catalytic steps are likely reversible, intramolecular dehydrative condensation of the azo and the alcohol moieties in the aldehyde adduct serves as a driving force for the formation of the indazole product. The reaction shows a substrate scope comparable to that of the same reaction catalyzed by a Cp Rh catalyst [36] and is applicable to both symmetrical and unsymmetrical azobenzene derivatives and to aromatic, heteroaromatic, and aliphatic aldehydes. 

Heteroaromatics LDA (and LiTMP) are advantageous bases for the directed ortto-metalation chemistry of pyridines and, to a much lesser extent, pyrimidines.Several halopyridines can be lithiated ortho to the halo substituent and trapped with various electrophiles (eq 55). ... 

Secondary amides as ortho-directed metallation groups for arenes a useful construction way for polysubstituted aromatic and heteroaromatic systems 06COC1817. 

On the way to further extension of the scope of Cp Co "-catalyzed C-H functionalization, Glorius and coworkers developed a condensation reaction of 2-arylpyridine derivatives and diazoesters to form unique polycyclic heteroaromatics having 6//-pyrido[2,l-a]isoquinolin-6-one skeletons (Scheme 10.15) [38]. The reaction is achieved by the combination of a bench-stable Co precatalyst [Cp Co(CO)l2] [39], a silver salt (AgSbFg), and an acetate source (KOAc) in trifluoroethanol. The in situ-formed Cp Co catalyst is proposed to play a dual role in this condensation reaction. First, it promotes formal carbene insertion into the ortho C-H bond through pyridine-directed C-H metalation, cobalt-carbene formation, carbene insertion into the aryl-Co bond, and protodemetalation. Second, it acts as a Lewis acid to facilitate nucleophilic attack of the pyridine moiety to the ester group, which eventually leads to the product through aromatization and elimination of methanol. The thus-synthesized polycyclic heteroarenes exhibit bright and color-tunable fluorescence in solution and in the solid state. 

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