Intramolecular hydride transfer onto arynes: redox-neutral and transition metal-free C(sp³)–H functionalization of amines

Abstract

Novel intramolecular hydride transfer onto arynes is exploited in a redox-neutral intermolecular α-functionalization of amines with diverse pronucleophiles.

Redox-triggered dearomative [5 + 1] annulation of indoles with O-alkyl ortho-oxybenzaldehydes for the synthesis of spirochromanes

“…8a,11e At the outset, the Knoevenagel condensation occurs between 2-methylindolenine and N-alkyl ortho-aminobenzaldehydes in the presence of Sc(OTf ) 3 , furnishing the vinylogous imine III. Then the electrophilic vinylogous imine is activated by Sc(OTf ) 3 to initiate the [1,5]-hydride transfer to generate the zwitterionic intermediate IV. Finally, intermediate IV undergoes nucleophilic cyclization to form a new N-heterocycle.…”

“…4 Great progress has been made in the field of hydride transfer in recent years, and a series of appealing polycyclic compounds have been furnished by this strategy. [4][5][6][7][8] Very recently, the combination of the hydride transfer process with dearomatization reactions, 6 and multiple C(sp 3 )-H bond functionalization reactions 7 further pushed forward the application of this strategy for the construction of architecturally complex molecules. For instance, indoles and phenols have been reported to react with o-aminobenzaldehydes by in situ assembly via the [1,5]-hydride transfer/cyclization process to achieve dearomatization for the synthesis of highly functionalized spiroindolenines and spirocyclohexaketenes, respectively.…”

Aryne-Mediated Arylation of Hantzsch Esters: Access to Highly Substituted Aryl-dihydropyridines, Aryl-tetrahydropyridines and Spiro[benzocyclobutene-1,1′-(3′,4′-dihydropyridines)]

“…This tentatively suggested a concerted mechanism, as the postulated stepwise intermediate 18 (Scheme 6, b) would be expected to deprotonate the solvent (acetonitrile) in at least trace amounts. 16 Once again, DFT calculations (B3LYP-D3/def2-TZVP in acetonitrile) 21 offered good support to the experimental evidence. Analysis of HE 13a revealed an energy barrier of 9.7 kcal/mol for the ene reaction, whereas no TS for the stepwise process was found.…”

“…13,14 As a result of these advancements, a number of exciting new modes of reactivity have been discovered. 15 There is very little known about hydride transfer onto arynes; we recently developed the first examples of an intramolecular reaction, 16 but there are no reports of an intermolecular variant. Conversely, the general propensity for arynes to participate in ene reactions is well-documented, with a number of intramolecular 17 and intermolecular [18][19][20] processes having been described.…”

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

“…if the aryne was already substituted). [22][23][24] Owing to this, aryne chemistry has emerged as a very useful method for the synthesis of benzo-fused heterocycles. 25 Of particular relevance to this article is the use of aryne chemistry to synthesise indazoles, i.e.…”