Para-Selective Dehydrogenative Phenothiazination of Hydroquinolines and Indolines

Abstract

Nitrogen-containing heterocyclic systems, such as hydroquinolines, indolines, and phenothiazines, are prevalent in pharmaceuticals, natural products, and organic materials. It is therefore important to develop novel reaction strategies that give access to such biologically relevant scaffolds. This report demonstrates a novel robust, para-selective C–N bond formation between phenothiazines and quinolines or indolines under extremely mild and user-friendly conditions. Furthermore, we bring forward a surprising discovery arising from the homocoupling of indolines through an unprecedented C5-H functionalization.

Iron-Mediated Selective Sulfonylmethylation of Aniline Derivatives with p-Toluenesulfonylmethyl Isocyanide (TosMIC)

“…On the basis of above discussion and previous literature reports, , a plausible reaction mechanism was proposed (Scheme ). Initially, Fe 2+ coordinated with isocyanide to form intermediate A .…”

“…Nevertheless, the general methodology for direct functionalization of anilines at the para position remains to be developed . In the case of indolines, only limited C5-functionalization has been reported, including difluoromethylation, nitration, chalcogenation, alkylation, olefination, and amination (Scheme c) …”

Photocatalyzed Chemo‐Selective Alkylation of Quinones and Phenothiazinones with Alkyl Amides: Photophysical and Cytotoxic Activity Studies

“…Phenothiazin‐5‐ones (PTZs), a non‐linear analog of phenothiazine, shows superior industrial and medicinal applications(Figure 1b) [7a–c] . Although PTZs shows characteristics such as excellent conjugation, redox activity, similar to quinones,there are only limited number of methods reported for C−H functionalization, [8a–d] and among which C−C bond forming approaches are only rare [9] . Furthermore, these methods have some shortcomings such as use of transition metal catalyst, [9a,b] expensive ligand, [9b] and pre‐functionalized starting materials [9d] .…”

Gold‐catalyzed C−H Functionalization of Phenothiazines with Aryldiazoacetates

“…[3] This radical formation can be easily induced by chemical oxidants, photoredox catalysis, or electrochemistry. [4] Owing to the nature of this radical reactivity, however, the majority of structural variations on the phenothiazine framework are limited to its N-functionalization (Scheme 1, 2). [4] Upon protection of the NÀ H group, it is possible for phenothiazines to undergo CÀ H functionalization on one of its flanking benzannellated rings via a similar radical mechanism (Scheme 1, 3), but examples of this pathway are scarce in literature.…”

“…[4] Owing to the nature of this radical reactivity, however, the majority of structural variations on the phenothiazine framework are limited to its N-functionalization (Scheme 1, 2). [4] Upon protection of the NÀ H group, it is possible for phenothiazines to undergo CÀ H functionalization on one of its flanking benzannellated rings via a similar radical mechanism (Scheme 1, 3), but examples of this pathway are scarce in literature. [5] The incorporation of a functional group on one of its flanking benzannellated rings can also be the chemical space constructed from the functionalization on their heteroatoms.…”