1,3‐Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4‐Dihydroisoquinoline toward Aryl Iso(thio)cyanates

Abstract

Unsubstitutedand 1-methyl-substituted 1,3,4,8btetrahydrodiazirino[3,1-a]isoquinolines (diaziridines 1 and 2) demonstrate different reactivities toward aryl isocyanates and aryl isothiocyanates. Diaziridine 1 reacts with aryl isocyanates as a nucleophile to afford novel 1,5,6,10btetrahydro[1,2,4]triazolo[5,1-a]isoquinolines. The addition of a Lewis or Brønsted acid switches the reaction pathway, producing seven-membered 2,3-benzodiazepines. In reactions of diaziridine 1 with aryl isothiocyanates, unusual zwitterionic compounds -2-thioxo-5,6-dihydro-2H-[1,2,4]triazolo[5,1a]isoquinolin-1-ium-3-ides -and products of the addition of two molecules of diaziridine 1 to one molecule of aryl isothiocyanate are obtained. However, in reactions with aryl iso(thio)cyanates under heating or acid catalysis, diaziridine 2 is first converted into an azomethine imine, the 1,3-dipolar cycloaddition of which to the dipolarophile produces substituted triazolo[5,1-a]isoquinolin-2(3H)-(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Brønsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts.

Access to pyrrolines and fused diaziridines by selective radical addition to homoallylic diazirines

“…These fused diaziridines might serve as versatile precursors for various N-heterocycles according to published approaches. 13 The reaction leading to fused diaziridines was initiated by the reductive quenching of excited fac -Ir(ppy) 3 with the Hantzsch ester to form an Ir( ii ) species. Its strong reduction potential ( E III/II 1/2 = −2.19 V vs. SCE) enables single-electron reduction of the N N bond of diazirine ( E RE 1/2 = −2.06 V vs. SCE) to an N-centered radical anion (for details, see the ESI ‡ ), and this is followed by a sequence of intramolecular cyclization, HAT and protonation.…”