Iodine‐Promoted Synthesis of Dipyrazolo/Diuracil‐Fused Pyridines and o‐Amino Diheteroaryl ketones via Oxidative Domino Annulation of 2/4‐Methylazaarenes

Abstract

The iodine‐promoted oxidative domino annulation and carbonylation process has been developed for the synthesis of biologically important azaarene‐substituted bis‐pyrazolo[3,4‐b:4′,3′‐e]pyridines (BPPs), diuracilpyridines and o‐amino diheteroaryl ketones. The domino procedure proceeded with easily available methyl azaarenes, 5‐aminouracils and substituted 5‐aminopyrazoles. This protocol is a simple and metal‐free approach which exhibits high functional group compatibility and broad substrates scope. Moreover, this transformation can be applied for the preparation of dipyrazolo/diuracil‐fused pyridines on a gram scale.

Electrochemical synthesis of dipyrazolo/dipyrimidine-fused pyridines via oxidative domino cyclization of C(sp3)–H bonds

“…From the above control experiments and previous reports, [4][5][6]13 a possible reaction mechanism was proposed using 2-methylquinoline (1a) and 3-methyl-1-phenyl-1Hpyrazol-5-amine (2a) as an example (Scheme 7). Initially, the electrogenerated molecular iodine reacts with the isomer 2-methylquinoline 1a′ to give 2-(iodomethyl)quinoline 8.…”

“…2 Consequently, continuous efforts have been focused towards constructing various dipyrazolo-fused pyridines. [3][4][5][6] Traditionally, the dipyrazolo-fused pyridines were constructed from pyrazol-5-amines and aromatic aldehydes via a three component reaction. 3 Nevertheless, high temperature was required to achieve efficient transformations.…”

“…During the preparation of this paper, an iodine-promoted reaction of methyl azaarenes with 6-aminopyrimidine-2,4-diones and pyrazol-5-amines for the synthesis of dipyrazolo/dipyrimidine-fused pyridines was also reported by Zhu and co-workers (Scheme 1c). 6 However, most of the reactions required the employment of metals or stoichiometric amounts of oxidants, leading to poor atom economy and undesirable wastes. Moreover, the substrate scope was usually restricted to methyl ketones or methyl azaarenes, hindering the practical application of these developed approaches.…”

Copper-Mediated C4-Benzylations of 5-Aminopyrazoles with 3-Indoleacetic Acids

“…Many bioactive 5-aminopyrazoles have a C4 substituent, and research has focused on developing synthetic methods for C4-functionalization of these compounds. However, the reported methods mainly involved the oxidative couplings with heteroatomic nucleophiles, which have considerable limitations . To our knowledge, a C4-benzylation of 5-aminopyrazoles has not yet been explored.…”

Generation of azaarene nitrile oxides from methyl azaarenes and t-BuONO enabling the synthesis of furoxans and 1,2,4-oxadiazoles

“…11 But, the method for furoxan and 1,2,4-oxadiazole synthesis using tert -butyl nitrite (TBN) as the NO source to assemble with methyl azaarenes has not been developed. Inspired by our ongoing interest in methyl azaarene sp 3 C–H functionalization, 12 herein we reported a novel and efficient dimerization reaction involving multiple molecules of methyl azaarenes for the synthesis of furoxans and 1,2,4-oxadiazoles using TBN as the nitrogen and oxygen source.…”