Multi-step radical spiro-cyclization of an alkynylaryl isothiocyanate

Abstract

Cyclohexyl radicals, generated by decomposition of dibenzoyl peroxide in cyclohexane, add to 2-(2-phenylethynyl)phenyl isothiocyanate to afford thioimidoyl radicals. Despite the unfavorable fragmentation equilibrium, these radicals give rise to a multi-step cyclization/H-translocation process yielding a spiranic polycondensed heterocyclic compound. An analogous spiranic dihydro-derivative is obtained by reaction of the corresponding alkynyl isonitrile with cyclohexanethiol under radical conditions.

Thiyl Radicals: Versatile Reactive Intermediates for Cyclization of Unsaturated Substrates

“…Analogous to those results by Rainer and co-workers, Minozzi et al published a similar radical cyclization of an alkynyl arylisonitrile 213 [98]. Interestingly, this proceeded as a multi-step cascade which resulted in the formation of quinoline 220 (Scheme 33, Insert A), as well as formation of spirocycles 218 and 219.…”

“…[95][96][97] Analogous to those results by Rainer and co-workers, Minozzi et al published a similar radical cyclization of an alkynyl arylisonitrile 213. [98] Interestingly, this proceeded as a multi-step cascade which resulted in the formation of quinoline 220 (Scheme 33, Insert A), as well as formation of spirocycles 218 and 219. The authors propose that the thioimidoyl radical 214 formed from thiyl addition to the isonitrile can cyclize onto the alkyne as previously shown, but a 1,5-hydorgen migration and cyclization then furnishes the observed spirocyclic compounds.…”

Reaction mechanisms : Part (i) Radical and radical ion reactions

“…Several other examples of so-called ''tandem'' or ''cascading'' rearrangements involving radicals and/or radical ions were reported in 2006. [93][94][95][96][97][98][99][100] Radical and radical ion rearrangements can be used in the context of kinetic and/ or mechanistic tools. For example, the cyclopropylcarbinylhomoallyl radical rearrangement was used to probe for the intermediacy of radicals in the Co- catalyzed, trimethylsilylmethylmagnesium-promoted alkenylation of alkyl halides (Scheme 28) 101 and the mechanism for the alkylation of phthalodinitrile radical anions.…”

Synthesis of 2-Alkoxy(aroxy)-3-substituted Quinolines by DABCO-Promoted Cyclization of o-Alkynylaryl Isocyanides

“…Having this idea in mind, we initiated the study with o -(phenylethynyl)phenyl isocyanide 2a and phenol 3a as substrates under various conditions as summarized in Table . Because o -alkynylaryl isocyanides are unstable especially at high concentration, they are used directly after dehydration of the corresponding N -formylamide and subsequent aqueous sodium bicarbonate workup . No desired cyclization product was observed by screening of inorganic (Na 2 CO 3 , NaH) and organic bases (pyridine, Et 3 N) (entries 1−4, Table ).…”