A facile route to 1H- and 2H-indazoles from readily accessible acyl hydrazides by exploiting a novel aryne-based molecular rearrangement

Abstract

Herein we report the transformation of readily synthesised acyl hydrazides into 2-hydrazobenzophenones via a novel molecular rearrangement pathway using aryne chemistry. The developed reaction protocol is performed under relatively mild conditions and is tolerant of a wide variety of functional groups, and the 2-hydrazobenzophenone products provide access to both 1H- and 2H-indazoles from a single intermediate.

Azabicyclic vinyl sulfones for residue-specific dual protein labelling

“…In another example, Gonçalves and co-workers reported dichlorotetrazine as a trivalent platform for conjugation to cysteine and showed dual labelling of albumin with a macrocyclic chelator for simultaneous nuclear imaging and a fluorescent probe for imaging 6. In addition, Chudasama, Caddick and co-workers have explored dibromopyridazinedione reagents that are able to site-specifically redbridge disulfide bonds and—at the same time—leave two click-reactive handles available for subsequent modifications with fluorophores, PEG derivatives or drugs through strain-promoted or copper-mediated azide–alkyne cycloaddition reactions 4,7,8. Water-soluble allyl sulfones were also shown by Weil and co-workers to rebridge disulfides whilst enabling dual protein functionalisation 9.…”

Synthesis of N‐Aryl‐ and N‐Alkenylhydrazides through C(sp2)−N Bond Construction

“…In 2018, Chudasama and co‐workers utilized N ‐acylhydrazides 162 as a hydrazine source to realize a novel aryne‐based molecular rearrangement with the formation of 2‐hydrazobenzophenones 163 (Scheme 41). [72] The whole process could be regarded as aromatic acyl and hydrazino nitrogen of 162 added to two sides of aryne. The use of tetrabutylammonium difluorotriphenylsilicate (TBAT) rendered the forging of 163 in 48–86 % yields.…”

Recent advances in metal-free aerobic C–H activation

“…Acyl hydrazides are extremely useful synthetic intermediates which have found use in the formation of many medicinally desirable entities (amides, indazoles, hydroxamic acids, etc.). [17][18][19][20][21][22] Both diethyl azodicarboxylate (DEAD) and diisopropyl azodicarboxylate (DIAD) were shown to be compatible with both aliphatic and aromatic aldehydes towards hydroacylation via aerobic C-H bond activation. The efficiency of the reaction was clearly demonstrated with excellent yields being attained even when utilising aldehydes as the limiting reagent.…”