Merging C–H Bond Functionalization with Amide Alcoholysis: En Route to 2-Aminopyridines

Abstract

A new route for the synthesis of 2-aminopyridines has been developed that merges C–H functionalization with amide alcoholysis. The key component of this method is the ability of a quinazolinone to template the chemo- and regioselective construction of a latent pyridine ring via site-selective olefinic C–H bond functionalization under Ru­(II) catalysis. Thus, highly substituted 2-aminopyridines were prepared in good yield. Mechanistic studies provide insight into the mechanism of the key oxidative C–H activation/annulation process.

Cobalt(III)‐Catalyzed Synthesis of Fused Quinazolinones by C–H/N–H Annulation of 2‐Arylquinazolinones with Alkynes

“…Based on the reported metal‐catalyzed directing group assisted C–H bond activation, and exposure in C–H and N–H bond formation reactions, a suitable mechanism is proposed to account for the present cobalt‐catalyzed reaction (Scheme ). The catalytic reaction likely starts with the removing of iodide ligand/followed by Cu(OAc) 2 ligand exchanges from the Co III complex with aid of AgSbF 6 salt.…”

“…In this context, Ru II ‐catalyzed annulation of quinazolones with alkynes has been demonstrated by Peng et al in 2014 . Later on, Cook and co‐workers developed a Ru II ‐catalyzed solvent controlled selective synthesis of 2‐aminopyridines and 3H ‐quinazolin‐4‐ones by C–H/N–H annulation strategy (Scheme a) . Nagaiah and co‐workers reported a ruthenium‐catalyzed cyclization of dihydroquinazolinones with alkynes .…”

Well-Defined Pre-Catalysts in Amide and Ester Bond Activation

“…Transition metal-catalyzed cross-coupling reactions to form C–C and C–N bonds are a mainstay of organic synthesis for a wide range of academic and industrial applications [1,2,3,4,5,6]. Due to their wide applicability, these reactions have become a critical arsenal for synthetic chemists and have clearly changed retrosynthetic analysis of complex targets.…”

Associative Covalent Relay: An Oxadiazolone Strategy for Rhodium(III)‐Catalyzed Synthesis of Primary Pyridinylamines

“…[7] Indeed as expected, virtually all of the pyridine synthesis protocols developed thus far focused exclusively on the construction of six-membered ring skeleton (Scheme 2b,l eft). [9] Thec umbersome reaction system for the tandem approach, however, translates directly to several inevitable drawbacks:1 )bulky substituent left intact on the amino group,2 )synthetic restriction to secondary amine, 3) required use of an external oxidant, and 4) not being step and atom economic.T he plight calls for ar evamping of the synthetic scheme and oxadiazolone proves to be the ideal choice for addressing the issues,w hich allows for efficient synthesis of primary pyridinylamines. [9] Thec umbersome reaction system for the tandem approach, however, translates directly to several inevitable drawbacks:1 )bulky substituent left intact on the amino group,2 )synthetic restriction to secondary amine, 3) required use of an external oxidant, and 4) not being step and atom economic.T he plight calls for ar evamping of the synthetic scheme and oxadiazolone proves to be the ideal choice for addressing the issues,w hich allows for efficient synthesis of primary pyridinylamines.…”