Cp*-Free Cobalt-Catalyzed C–H Activation/Annulations by Traceless N,O-Bidentate Directing Group: Access to Isoquinolines

Abstract

N,O-Bidentate directing-enabled, traceless heterocycle synthesis is described via Cp*-free cobalt-catalyzed C–H activation/annulation. The weakly coordinating nature of the carboxylic acid was employed for the preparation of isoquinolines. Meanwhile, the N–O bond of the α-imino-oxy acid can serve as an internal oxidant. Terminal as well as internal alkynes can be efficiently applied to the catalytic system. This operationally simple approach shows a broad substrate scope with the products obtained in good to excellent yields.

Traceless Directing Groups in Sustainable Metal-Catalyzed C–H Activation

“…Upon experimentation on the substrate scope, the authors found that o-arylanilines with neutral (105), electron-donating (106), or electron-withdrawing substituents (107) on the para position of the ortho-aryl ring provided the targeted products in 90%−97% yield. Regarding meta-substituted substrates, regioselectivity was observed and products were generated from carbonylation of the less sterically congested C-H bond (108). However, the reaction was not as competent against ortho-substituted substrates, where products were received in lower than 90% yields (109), due to steric effects.…”

“…Co-catalyzed, 2-hydrazinylpyridine-directed C-H alkenylation with alkynes and its application on a naturally-occurring substrate. Another protocol towards the Cp*-free, cobalt-catalyzed, TDG-assisted, synthesis of isoquinolines was reported by Song and co-workers in 2019 [108]. Substituted isoquinolines are important heterocyclic compounds found in chiral ligands and pharmaceuticals, amongst others.…”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…Under these reaction conditions wide range of α-imino-oxy acid and terminal as well as internal alkynes were reacted to obtain isoquinolines in good to excellent yields (Scheme 56). [84] Deshmukh et al reported the cobalt(III)-catalyzed annulations of azines 103 via CÀ H/NÀ N bond activation towards the synthesis of isoquinolines. This efficient approach explores the concept of atom economy for synthesizing wide range of isoquinolines.…”

“…Under these reaction conditions wide range of α‐imino‐oxy acid and terminal as well as internal alkynes were reacted to obtain isoquinolines in good to excellent yields (Scheme 56). [84] …”

N-Amino-7-azaindole as the N,N′-Bidentate Directing Group: Ruthenium-Catalyzed Oxidative Annulation of N-(7-Azaindole)benzamides with Alkynes via C–H Bond Activation

“…Directing group-assisted transition-metal-catalyzed C–H activation and annulation reaction has been utilized for the synthesis of numerous biologically important molecular scaffolds such as isoquinolines, isoquinolones, pyridines, and indoles, and so forth. Ever since the discovery of 8-aminoquinoline as a directing group for C–H activation reactions by Daugulis et al in the year 2005, it has become the most successful and widely used directing group for C–H activation reactions .…”