Sodium dithionite mediated one-pot, tandem chemoselective reduction/cyclization for the synthesis of pyrrole fused N-heterocycles

Abstract

A chemoselective reduction of nitro group in the presence of an aldehyde or ester group integrated with another synthetic transformation leading to the expedient synthesis of important heterocycles is the...

Metal- and Additive-Free Intramolecular Direct Amidation of Ester Functionality within a Nitroarene Framework: Facile Access to Azaheterocycles

“…Although Na 2 S 2 O 4 is the most sustainable alternative to conventional metal-based reduction, it has been underutilized for nitro reduction and other reductive transformations. , The key question is whether intramolecular direct amidation of esters with nitroarenes can be accomplished with Na 2 S 2 O 4 , enabling the preparation of diverse azaheterocycles. Recently, we reported Na 2 S 2 O 4 -mediated tandem chemoselective reduction/cyclization for the synthesis of pyrrole-fused N-heterocycles . Here, the in situ reduction of the nitro group followed by condensation with various aldehyde frameworks was largely explored, providing access to diverse pyrrolo­[1,2- a ]-quinoxalines and pyrrole-fused benzodiazepines.…”

Dithionite-Mediated Tandem Nitro Reduction/Imine Formation/Intramolecular Cyclization for the Synthesis of Dihydro-benzothiadiazine-1,1-dioxides

“…19 Previously, we reported Na 2 S 2 O 4 -mediated one-pot, tandem chemoselective reduction/cyclization for the synthesis of pyrrole-fused N-heterocycles. 20 Herein, we report a one-pot, tandem reductive annulation strategy involving 2-nitrobenzenesulfonamides and aromatic/aliphatic aldehydes to the synthesis of 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides utilizing Na 2 S 2 O 4 as the exclusive reagent under mild reaction conditions. Distinctly, the current method uses 2-nitrobenzenesulfonamides unlike 2-aminobenzenesulfonamides that are invariably used in the previous methods, which accounts for step economy (Scheme 1).…”

“…Thus, reaction of 1a and 2a under the optimized conditions however in the presence of 4 equiv of TEMPO did not yield 3a in a detectable quantity. Based on the control experiment and literature reports, 19,20 doublet; dt, triplet of doublet; t, triplet; m, multiplet. 13 C NMR spectra were recorded with complete proton decoupling.…”

“…Although Na 2 S 2 O 4 is historically used in the dye and textile industries, its use in organic transformations including nitro group reduction and subsequent transformations is underexplored . Previously, we reported Na 2 S 2 O 4 -mediated one-pot, tandem chemoselective reduction/cyclization for the synthesis of pyrrole-fused N -heterocycles . Herein, we report a one-pot, tandem reductive annulation strategy involving 2-nitrobenzenesulfonamides and aromatic/aliphatic aldehydes to the synthesis of 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides utilizing Na 2 S 2 O 4 as the exclusive reagent under mild reaction conditions.…”

“…Thus, reaction of 1a and 2a under the optimized conditions however in the presence of 4 equiv of TEMPO did not yield 3a in a detectable quantity. Based on the control experiment and literature reports, , a plausible reaction mechanism is depicted in Scheme b. Initially, a powerful single-electron reductant, sulfoxylate anion radical (SO 2 –• ), is generated by the homolytic cleavage of the dithionite anion (S 2 O 4 –• ), which transfers electrons to 1a to generate a nitroso intermediate 1a′ .…”