Easy Access to 1‐Amino and 1‐Carbon Substituted Isoquinolines via Cobalt‐Catalyzed CH/NO Bond Activation

Abstract

A green atom‐economical method for the synthesis of highly functionalized 1‐amino and 1‐carbon substituted isoquinolines from the reaction of N′‐hydroxybenzimidamides and aryl ketoximes, respectively, with alkynes via pentamethylcyclopentadienylcobalt(III)‐catalyzed CH/NO bond activation is described. The external oxidant‐free annulation reaction uses the =NOH moiety in N′‐hydroxybenzimidamides or N‐aromatic ketone oximes as the directing group and internal oxidant. This first row transition metal‐catalyzed annulation serves as an efficient alternative for the synthesis of isoquinolines, as water is the only by‐product and expensive noble metals such as rhodium(III), iridium(III), palladium(II), and ruthenium(II) are not required. The reaction proceeds via CH activation, alkyne insertion, reductive elimination, and NO activation.magnified image

Cobalt‐Catalyzed Annulation Reactions via C−H Bond Activation

“…The transition‐metal catalyzed synthesis of isoquinolines via redox‐neutral strategy is well documented in the literature and in that context, many noble metals have been used . Nonetheless, Co III ‐catalyzed redox‐neutral directed synthesis of isoquinolines was not reported and very recently, this was independently achieved by Kanai/Matsunaga, Ackermann, Sundararaju, and Cheng from the coupling of various oximes with alkynes. A variety of functional groups on oximes and different type of alkynes, including aliphatic alkynes, terminal alkynes were well tolerated, and excellent regioselectivity was observed with internal alkynes under these reaction conditions.…”

Synthesis of Isoquinoline Derivatives via Palladium‐Catalyzed C−H/C−N Bond Activation of N‐Acyl Hydrazones with α‐Substituted Vinyl Azides

“…Recently, transition-metal-catalyzed direct CÀ H functionalization has emerged as a novel strategy to construct isoquinoline skeleton by CÀ H/NÀ N bond activation or CÀ H/NÀ O bond activation with nitrogen-containing directing groups including aromatic hydrazines, imines, azines oximes, etc. [6][7][8][9] In most cases, internal nitrogen source of isoquinolines was also provided by directing groups.…”

Theoretical prediction on the synthesis of 2,3‐dihydropyridines through Co(III)‐catalysed reaction of unsaturated oximes with alkenes

“…So far, the majority of developed CH activation methods employ catalysts based on noble transition metals such as Ru, Rh, Pd, or Ir . More recently, earth‐abundant and cost‐efficient first‐row transition metals, especially Co, have emerged as attractive alternatives to the noble metals . Among them, the Cp*Co(III) catalysts not only emulate the known catalytic capabilities of Cp*Rh(III) efficiently, but also exhibit other unique reactivities .…”