Mechanochemical Ni‐Catalysed Arylation of ortho‐Hydroxyarylenaminones: Synthesis of Isoflavones

Abstract

This work describes two new synthetic methods for the preparation of isoflavones following the Nicatalysed domino arylation reactions of the vast range of ortho-hydroxyarylenaminones utilising aromatic bromides as well as carboxylic acids. The presented protocols tolerated significant variation of all coupling partners and enabled synthesis of isoflavone library of twenty-three representatives. This is the first communicated precedent where the mechanic energy was utilised in the synthesis of isoflavones following the domino cyclisation mode.

Introducing Trifluoromethoxyarenes as Halide Surrogates in Mechanochemical Realizations of Ni‐catalyzed Cross‐coupling Reactions

“…Encouraged by the results of our previous attempts to realize catalytical processes under mechanochemical conditions [41][42][43] we made our rule to extend any search for ORCs to include solid-phase conditions. The solid-phase reaction kinetics are governed by completely different rules.…”

Mechanochemical Defluorinative Acylation of ortho‐Hydroxyarylenaminones by CF3‐Compounds: Synthesis of 3‐Acylchromones

“…Continuing our ongoing research devoted to developing new strategies for the late‐stage functionalization of CF 3 ‐containing compounds, utilizing mechano‐milling conditions, we consider the utilization of the complex push‐pull nucleophiles like ortho ‐hydroxyarylenaminones 1 for the synthesis of 3‐acylchromones 3 following the domino cyclisation mode. Of note, very recently we have developed three synthetic methods utilizing mechano‐milling conditions that enabled the synthesis of aryl trifluoromethyl ethers from aromatic amines, [54] aromatic amides by defluorinative arylation of trifluoroacetamides [55] and the domino synthesis of isoflavones by Ni‐catalyzed direct arylation of ortho ‐hydroxyarylenaminones utilizing aromatic bromides or carboxylic acids as arylating reagents (Scheme 1c) [56] …”

“…Of note, very recently we have developed three synthetic methods utilizing mechano-milling conditions that enabled the synthesis of aryl trifluoromethyl ethers from aromatic amines, [54] aromatic amides by defluorinative arylation of trifluoroacetamides [55] and the domino synthesis of isoflavones by Ni-catalyzed direct arylation of ortho-hydroxyarylenaminones utilizing aromatic bromides or carboxylic acids as arylating reagents (Scheme 1c). [56]…”

Nanocellulose as Convenient Reaction Media for the FeCl3 Mediated Mechanochemical Synthesis of 3-Acylchromones

“…42,43 Very recently, we have developed an alternative strategy for the mechanochemical defluorinative acylation of ortho-hydroxyarylenaminones to synthesize 3-acylchromones using CF 3 − compounds via activation of the C−F bound of the trifluoromethyl group in the presence of Yb 2 O 3 (Scheme 1). 44 However, these methods still have limited pharmaceutical relevance because they use toxic and expensive transition-metal catalysts, ligands, and oxidants, along with the limited pool of expensive chromone substrates and prolonged reaction times. Thus, there is an urgent need to develop an environmentally benign and cost-effective protocol to access 3-acylchromones using readily available starting materials and nontoxic catalysts.…”

“…As a renewable natural material, nanocellulose is not only biodegradable, but also contains many hydroxyl groups exhibiting strong water absorption/scavenging properties . Nanocellulose also possesses a high specific surface area, high crystallinity and chirality, superior mechanical strength, and controllable surface chemistry. − Utilizing the aforementioned characteristics features of nanocellulose, and in continuation of our long-standing interest for the development of novel, efficient and concise routes toward the synthesis of 3-functionalized chromones, − we envisioned that 3-acylchromones may be mechanochemically synthesized via FeCl 3 catalyzed dehydrative coupling of ortho -hydroxyarylenaminones and carboxylic acids utilizing nanocellulose as nontoxic and biocompatible reaction media.…”