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

Abstract

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 (SO 2 −• ), generated in situ from the reagents rongalite or sodium dithionite (Na 2 S 2 O 4 ), 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.

Rongalite-Mediated Transition Metal- and Hydride-Free Chemoselective Reduction of α-Keto Esters and α-Keto Amides

“…Based on the control experiments and previous literature reports, a plausible mechanism is proposed in Scheme . Initially, the reductant rongalite dissociates itself into formaldehyde and HSO 2 – .…”

“…Sodium hydroxymethanesulfinate dihydrate (SHM), commonly known as rongalite, is a commercially inexpensive (0.03$/1 g) industrial product, and Kotha and co-workers widely used rongalite in organic synthesis. , It acts as a super-electron donor, a source of C1 unit, and a sulfoxylate dianion (SO 2 2– ) . In continuation of our efforts to explore the synthetic utility of rongalite as an electron source and in hydride-free reduction, herein, we report a chemoselective transition metal- and hydride-free protocol to prepare α-hydroxy esters/amides from the respective α-keto esters/amides by exploring the super-electron-donating nature of rongalite.…”

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C−H Bonds

“…Phenanthridin ( 6 ) [ 57 ]: A stock solution was prepared by dropwise addition of concentrated sulfuric acid (1 mL) to reagent-grade methanol (5 mL) in a scintillation vial (20 mL in volume). The stock solution was stirred for 5 min, and then the solution was cooled to room temperature.…”

Recent Developments in Rongalite Chemistry: A Critical Review

“…Keeping the importance of cyclic sulfonamide framework i. e. biarylsultam – a privileged scaffold in “drug discovery & drug‐like pharmaceuticals” in mind, very recently Laha et al ., have developed a simple, greener & practical method to assemble a variety of biarylsultams through SO 2 − ⋅ (generated in situ from cheap & commercially available industrial reagents, namely, rongalite) promoted intramolecular C( sp 2 )−H arylation from the inexpensive & commercially available 2‐bromo‐arylsulfonamides (scheme 16). [34] Interestingly, by using this versatile strategy, diverse 6‐ & 7‐membered biarylsultams (with free NH‐group – amenable to the further functionalization) were successfully prepared in excellent yields. The utility of this procedure was demonstrated by exploring the broad substrates scope in addition to a gram‐scale synthesis under green condition without involving any transition metal.…”