Cascade Radical Reactions via α-(Arylsulfanyl)imidoyl Radicals:  Competitive [4 + 2] and [4 + 1] Radical Annulations of Alkynyl Isothiocyanates with Aryl Radicals

Abstract

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.

Intermolecular Olefin Functionalisation Involving Aryl Radicals Generated from Arenediazonium Salts

“…[74] Cascade reactions leading to complex heterocycles that are based on an aryl radical attack on isothiocyanates and subsequent intramolecular cyclisations have also been reported recently. [75] Chlorine Starting with the first publication by Meerwein in 1939, [28] continuous efforts have been made to further improve the original protocol with regard to both yield and access to new product types. [29] Although remarkable progress has been reported in these fields, the exact mechanism of the Meerwein arylation is still not fully understood.…”

Pd‐Catalyzed [2+2+1] Coupling of Alkynes and Arenes: Phenol Diazonium Salts as Mechanistic Trapdoors

“…[45] Yet another reaction that has to be taken into account is the in situ formation of aryl radicals and their addition to alkynes. [46,47] Intrigued by this multifaceted reactivity and by the mechanistic ambiguity of the double carbopalladation initiated by Pd-s-aryl complexes (see Schemes 2 and 3), we investigated the reaction of alkynes and phenol diazonium salts under Pd 0 catalysis. In this contribution, we report the results obtained in the course of this study and discuss possible implications on the understanding of Pd-catalyzed formal [2+2+2] cycloaddition reactions involving aryl electrophiles and alkynes.…”

Base‐Promoted Aerobic Oxidation/Homolytic Aromatic Substitution Cascade toward the Synthesis of Phenanthridines

“…The reaction initiates by the interaction between the ligand phenanthroline (Phen) and KO t Bu to generate the radical anion 5 via an inner-sphere electron transfer process. [22] Herein, we report a transition metal-free aerobic oxidation of alcohol and direct condensation reaction with amine to form a CÀ N bond followed by a CÀ C coupling in a cascade sequence to achieve the targeted phenanthridine. Alternatively, in situ formed dimeric heterocyclic structures as electron donors, as suggested by Murphy, cannot be ruled out.…”