The reactivity of allenes in transition-metal-catalyzed C-H activation chemistry is governed by the formation of either alkenyl-metal (M-alkenyl) or metal-π-allyl intermediates. Although either protonation or a β-hydride elimination is feasible with a M-alkenyl intermediate, cyclization has remained unexplored to date. Furthermore, due to the increased steric hindrance, the regioselectivity for the intramolecular cyclization of the metal-π-allyl intermediate was hampered towards the more substituted side. To address these issues, a unified approach to synthesize a diverse array of biologically and pharmaceutically relevant heterocyclic moieties by cobalt-catalyzed directed C-H functionalization was envisioned. Upon successful implementation, the present strategy led to the regioselective formation of dihydroisoquinolin-1(2H)-ones, isoquinolin-1(2H)-ones, dihydropyridones, and pyridones.

A convergent strategy for the synthesis of biologically relevant C4-substituted indole scaffolds was demonstrated using Pd(II)-catalyzed remote CÀH functionalization of indoles and azaindoles. The reaction displays high regioselectivity for the C4-position of indole-3-carbaldehydes using glycine as an inexpensive transient directing group. Notable features of this transformation include the selective formation of six-membered palladacyle and excellent functional group tolerance.

A bidentate chelation-assisted cobalt-catalyzed C­(sp2)–H activation and annulation of benzamides and alkylidenecyclopropanes (ACPs) has been realized. The unique reactivity of organocobalt species led to selective migratory insertion across the more electron-rich CC bond of the ACP followed by faster reductive elimination from the seven-membered cobaltacycle leading to spiro-dihydroisoquinoline derivatives with conservation of the cyclopropyl ring. The operationally simple reaction conditions allowed the C–H activation of both aryl and heteroaryl amides at room temperature.

An efficient cobalt-catalyzed [4 + 2] annulation of hydrazones and 1,3-diynes has been developed for the synthesis of 3-alkynylated isoquinolines engaging 2-aminopyridine as a traceless bidentate directing group. The strategy has been successfully extended for the synthesis of 3,3′-biisoquinoline moieties via both one-pot as well as sequential approaches. The utilization of a traceless bidentate directing group with an inexpensive and earth-abundant cobalt-catalyst under operationally simple reaction conditions makes the present transformation more valuable and appealing.

The development of a rational strategy for achieving site-selective C4−H halogenation of indoles is an appealing yet challenging task. Herein, we disclose a Pd(II)-catalyzed transient directing group (TDG)-assisted methodology for realizing C4 chlorination/bromination of indoles employing glycine as the TDG and NFSI as a bystanding oxidant. The use of inexpensive and commercially available CuX 2 as the halide source is the key highlight of this protocol. Furthermore, the TDG methodology was also extended to accessing C4 acetoxylated indoles employing acetic acid as the acetate source and 1-fluoro-2,4,6trimethylpyridinium triflate as the oxidant.