Expanding the Utility of Inexpensive Pyridine‐<i>N</i>‐oxide Directing Group for the Site‐selective sp²/sp³<i>γ</i>‐C−H and sp²<i>δ</i>‐C−H Functionalization of Carboxamides

Abstract

Abstract We 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(sp 2 )−H, γ ‐C(sp 3 )−H and δ ‐C(sp 2 )−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 sp 2 /sp 3 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(sp 2 )−H arylation in substrates containing competitive C(sp 3 )−H and C(sp 2 )−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 sp 2 /sp 3 γ‐ C−H and sp 2 δ‐ C−H functionalization of carboxamides.