Expanding the Utility of Inexpensive Pyridine‐N‐oxide Directing Group for the Site‐selective sp2/sp3γ‐C−H and sp2δ‐C−H Functionalization of Carboxamides

Abstract

AbstractWe have shown our efforts toward expanding the utility of the relatively inexpensive pyridine‐N‐oxide directing group in the Pd(II)‐catalyzed site‐selective γ‐C(sp2)−H, γ‐C(sp3)−H and δ‐C(sp2)−H functionalization. The functionalization β−C−H bonds using bidentate directing group (DG) pyridine‐N‐oxide which operates through the N,O‐coordination mode has been well documented in the literature. However, there exist rare reports dealing with the functionalization of remote sp2/sp3 γ‐ and δ‐C−H bonds of carboxamides assisted by the bidentate directing groups operating via the N,O‐coordination. In this paper, the scope of pyridine‐N‐oxide DG was examined for accomplishing the site‐selective (mono) γ‐C(sp2)−H arylation in substrates containing competitive C(sp3)−H and C(sp2)−H bonds. The investigation has enabled to assemble a library of pyridine‐N‐oxide‐based biarylacetamides, heteroaryl‐based biaryl carboxamides, tricyclic quinolones, arylheteroarylmethanes, biaryl‐based aliphatic carboxamides and mono (ortho) arylated phenylglycine derivatives. In general, biaryl derivatives and in particular, arylacetamide, arylacetic acid derivatives and pyridine‐N‐oxide (2‐aminopyridyl) motifs are medicinally relevant classes of compounds. This work enabled the assembling of a library of the above‐mentioned types of compounds through the pyridine‐N‐oxide directing group‐aided site‐selective sp2/sp3 γ‐C−H and sp2 δ‐C−H functionalization of carboxamides.