Aryl radical generation from the corresponding aryl halides using an electron donor and subsequent intramolecular cyclization with arenes could be an important advancement in contemporary biaryl synthesis. A green and practically useful synthetic protocol to access diverse six- and seven-membered biarylsultams especially with a free NH group including demonstration of a gram-scale synthesis is reported herein. The sulfoxylate anion radical (SO2-•), generated in situ from the reagents rongalite or sodium dithionite (Na2S2O4), was found to be the key single electron transfer agent forming aryl radicals from aryl halides, which upon intramolecular arylation gives biarylsultams with good to excellent yields. The approach features generation of aryl radicals that remained underexplored, use of a cheap and readily available industrial reagents, and transition metal-free, mild, and green reaction conditions.

Sulfoxylate Anion Radical-Induced Aryl Radical Generation and Intramolecular Arylation for the Synthesis of Biarylsultams.

By merging transition metal and heterogeneous photocatalyst, a metal-photoredox system has attracted more attention for cross-coupling of various dual photoredox catalysis. However, there is a grand challenge for the attenuated nucleophilicity of sulfonamides relative to alkyl amines. Herein, an integrated dual catalytic system of porous carbon nitride nanosheet with nitrogen vacancies (N V -P-C 3 N 4 ) as a conjugated polymer semiconductor host in combination with transition-metal nickel (Ni) was constructed by a defect and morphology regulation strategy toward visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides. The excellent nickel/photoredox-catalyzed C–N coupling reaction performance is ascribed to the large specific surface area, abundant active sites, long carrier lifetime, and efficient transfer and separation of photoexcited electrons and holes. This work highlights the opportunity to cooperate with heterogeneous catalysts and active metal sites for challenging cross-coupling reactions. • Dual catalytic system of photoredox and transition metal • Carbon nitride with defect and morphology characteristics • C–N cross-coupling • Heterogeneous catalysts are used for sulfonamidation reactions For the fine chemical and pharmaceutical synthesis communities, it is crucial to determine the formation of anilines through C–N bond transformation approach. Considerable progress has been reported on dual catalytic systems of homogeneous photocatalysts combined with transition metals. However, the progress of heterogeneous catalysts for dual catalysis has not been satisfactory. Carbon nitride (C 3 N 4 ) is a class of metal-free conjugated polymer semiconductor with great potential for photoredox/Ni dual catalytic cross-couplings due to its thermal and chemical stability, facile fabrication, and cheapness. Herein, porous carbon nitride nanosheets with nitrogen vacancies (N V -P-C 3 N 4 ) were fabricated by a defect and morphology regulation strategy for visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides. This work highlights the opportunity to cooperate with heterogeneous catalysts and active metal sites for challenging cross-coupling reactions. An integrated dual catalytic system of N V -P-C 3 N 4 in combination with transition-metal Ni was constructed toward visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides. This work not only realizes the sulfonamidation reaction in a heterogeneous catalytic system for the first time but also demonstrates that defect engineering and morphology strategies are effective for enhancing photoredox dual catalytic performance. 

Integrated nickel/polymer dual catalytic system for visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides

Nickel-Catalyzed Denitrogenative Cyclization of 1,2,3,4-Benzothiatriazin-1,1(2H)-dioxides with Arynes To Synthesize Biaryl Sultams.

Six- or seven-membered dibenzosultams were synthesized upon treatment of N-aryl- or N-benzyl-2-halobenzenesulfonamides with HCOONa·2H2O in DMSO without using additional measures and additives, such as light irradiation, electrochemical apparatus, transition metals, and oxidants. Further functionalization of the free NH group of the resultant dibenzosultams demonstrates the synthetic practicability of this method. 

Intramolecular Arylation of 2‐Bromobenzenesulfonamides Using DMSO/HCOONa·2H2O System: An Access To Dibenzosultams

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2-5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.

Design, Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.

Rafael Hortigüela

Papers

Design, Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.