Direct Thioamination of Cyclohexanones via Difunctionalization with Thiophenol and Aniline

Abstract

A synthetic method of o-sulfanylanilines from cyclohexanones, amines, and thiophenols under transition-metal-free conditions is disclosed. This is the first report on the direct thioamination of cyclohexanones via N-iodosuccinimide (NIS) promoted oxidative dehydroaromatization. Non-aromatic cyclohexanones were smoothly dehydrogenated, and acted as an aryl source using oxygen as a green oxidant. The capacity of the resultant o-sulfanylanilines for synthesis of N-arylphenothiazines has been further demonstrated.

Reductive thiolation and oxidative dehydroaromatization of cyclohexanones with primary amines and sodium sulfinates to access o-sulfanylanilines

“…Our continuous interest 9 in aminothiolation reactions led us to envision whether a dehydroaromatizing thioamination of cyclohexanones with primary amines and sodium sulfinates would provide a direct and concise pathway to access significant 1,2-aminothiolated arenes, which are ubiquitous in several pharmaceuticals and bioactive molecules (Scheme 1A). 10 However, this multi-component cascade reaction is a conceptual and underexplored challenge. (1) A compatibility issue exists between deoxygenative thiolation requiring reductive reaction conditions and dehydroaromatization requiring oxidative reaction conditions.…”

Substrate‐Dependent Divergent Oxyamination of beta‐Tetralones Enabling Modular Synthesis of 2‐Amino‐para‐Iminonaphthoquinones and 4‐Amino‐1,2‐Naphthoquinone Derivatives

“…In recent years, the research of our group and others has revealed that cyclohexanones and β-tetralones could be coupled with a variety of nucleophiles, including amines, for the synthesis of poly-substituted aromatics and heterocycles via dehydroaromatization. [10,11] Among them, a handful of metalfree difunctionalization of these substrates with various amines were developed with assistance of elemental sulfur and/or iodine, providing o-arylenendiamines, [12] o-sulfanylanilines, [13] phenothiazine, and phenazine derivatives, [14] respectively. However, the multi-functionalization of cyclohexanones and beta-tetralones has so far remained challenging and intriguing.…”

Aminoselenation and Dehydroaromatization of Cyclohexanones with Anilines and Diselenides

“…While numerous groundbreaking achievements have been made, most dehydrogenative functionalizations of cyclohexanone are predominantly focused on the introduction of new functional groups at the carbonyl α- or ipso- positions. In recent years, the dehydrogenation difunctionalization reaction strategy between cyclohexanone and two nucleophilic reagents has been used in the preparation of ortho-disubstituted arenes . As far as we know, a three-component deoxygenation difunctionalization reaction between cyclohexanone, nucleophilic reagents, and electrophilic reagents for preparing ortho-disubstituted arenes has not been achieved.…”