Aryne [3 + 2] cycloaddition with N-sulfonylpyridinium imides and in situ generated N-sulfonylisoquinolinium imides: a potential route to pyrido[1,2-b]indazoles and indazolo[3,2-a]isoquinolines

Abstract

The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N'-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents.

1,3-Dipolar cycloadditions of azomethine imines

“…43 In the case of using arynes as dipolarophiles and pyridinium imides 148 with different electron-withdrawing groups on the imide nitrogen, it was found that the pyrido[1,2-b]indazoles 155 are obtained in high yields (Scheme 58) using the tosyl derivatives 154, whereas the benzoyl, pivaloyl, benzyloxycarbonyl, and tert-butyloxycarbonyl ones gave lower results. 90 This methodology has been also used with N-tosylisoquinolinium imides to afford indazolo[3,2-a]isoquinolines.…”

Nucleophilic Nitrenoids Through π‐Acid Catalysis: Providing a Common Basis for Rapid Access into Diverse Nitrogen Heterocycles

“…The reactivity of N-substituted pyridinium N-aminides through their interaction with a p-acid-activated alkyne also contrasts with the usual reactivity arising from their innate 1,3-C,N-dipolar character employed in av ariety of transformations. [42] Ar elated formal [3+ +2]-cycloaddition approachu sing acyl sulfonium ylides alongside alkynes under gold-catalysis was independently reported by the groups of Skrydstrup andM aulide. [43] Garzón and Davies established that the formal [3+ +2]-dipolar cycloaddition concept can be applied more widely to the formationo fo ther azoles.…”

Selective Synthesis of Indazolo[2,3‐a]quinolines via Rh(III)‐Catalyzed Oxidant‐Free [4+2] or [5+1] Annulation of 2‐Aryl‐2H‐indazoles with α‐Diazo Carbonyl Compounds

“…[3] In view of their importance, several synthetic methods have been developed. For example, indazolo[2,3-a]quinolines could be obtained through the aryne [3 + 2] dipolar cycloaddition reactions, [4] the PPh 3 -mediated reductive cyclization of 2-(o-nitrophenyl)quinolines, [5] and the Pd-catalyzed tandem cross-coupling of 2-(o-iodophenyl)-2H-indazole with organozinc reagents. [6] While the above methods are effective, they usually suffer from the use of complex starting materials, limited substrate scope or multistep operation.…”

“…J = 8 4. Hz, 1H);13 C NMR (CDCl 3 , 100 MHz) δ 13.8, 61.8, 117.1, 117.6, 117.9, 121.1, 121.7, 121.8, 123.3, 125.8, 126.3, 126.9, 128.0, 129.5, 129.8, 130.0, 131.2, 132.0, 133.3, 134.5, 149.6, 166.9.…”