Cascade radical reactions via alpha-(arylsulfanyl)imidoyl radicals: competitive [4 + 2] and [4 + 1] radical annulations of alkynyl isothiocyanates with aryl radicals

Aryl radicals react with 2-(2-phenylethynyl)phenyl isothiocyanate through a novel radical cascade reaction entailing formation of alpha-(arylsulfanyl)imidoyl radicals and affording a new class of compounds, i.e. thiochromeno[2,3-b]indoles. These derivatives are formed as mixtures of substituted analogues arising from competitive [4 + 2] and [4 + 1] radical annulations. The isomer ratio is strongly dependent on the aryl substituent and is correlated to its capability to delocalize spin density. The presence of a methylsulfanyl group in the ortho-position of the initial aryl radical results in complete regioselectivity and better yields, as the consequence of both strong spin-delocalization effect, which promotes exclusive [4 + 1] annulation, and good radical leaving-group ability, which facilitates aromatization of the final cyclohexadienyl radical. Theoretical calculations support the hypothesis of competitive, independent [4 + 2] and [4 + 1] annulation pathways. They also suggest that rearrangement onto the sulfur atom of the [4 + 1] intermediate does not occur via a sulfuranyl radical but rather through either a transition state or a sulfur-centered (thioamidyl) radical; the latter is possibly the preferred route in the presence of an o-methylsulfanyl moiety that can act as a leaving group in the final ipso-cyclization process.