Enantioselective modification of sulfonamides and sulfonamide-containing drugs via carbene organic catalysis

Abstract

A carbene-catalyzed method for highly enantioselective modification of sulfonamides is disclosed. The reaction proceeds under mild conditions with broad substrate scope, wide functional group tolerance, and good to excellent yields....

Access to Planar Chiral Ferrocenes via N-Heterocyclic Carbene-Catalyzed Enantioselective Desymmetrization Reactions

“…Noteworthily, reducing the amount of the dialdehyde substrate 1a resulted in an obvious drop in the yield of 3a , with the nonchiral diester byproduct afforded in 10% to 30% yields in these cases (entries 13 to 14). In contrast to our previous studies with o -phthaladehyde substrates, no formation of the lactol acylation products was observed. This is probably because the formation of the monoesterificated product 3a is both kinetically and thermodynamically favored.…”

N-Heterocyclic Carbene-Catalyzed Facile Synthesis of Phthalidyl Sulfonohydrazones: Density Functional Theory Mechanistic Insights and Docking Interactions

“…Intermediate II converts into the acyl azolium intermediate III , with liberation of the hydroperoxy anion (oxidative path). The intermediate III further undergoes nucleophilic attack by deprotonated N -tosyl hydrazone, followed by O–C coupling to give intermediate IV through intramolecular annulation . The intermediate IV upon fragmentation may yield a phthalidyl sulfonohydrazone as the final product along with the regeneration of the active catalyst.…”

“…The intermediate III further undergoes nucleophilic attack by deprotonated N -tosyl hydrazone, followed by O–C coupling to give intermediate IV through intramolecular annulation. 14 The intermediate IV upon fragmentation may yield a phthalidyl sulfonohydrazone as the final product along with the regeneration of the active catalyst. In the following sections, we will discuss the detailed reaction mechanisms, including the formation of the Breslow intermediate, aerial oxidation of the Breslow intermediate, nucleophilic attack of deprotonated N -tosyl hydrazone, O–C coupling, and dissociation of the NHC catalyst.…”

A novel bioresponsive self-immolative spacer based on aza-quinone methide reactivity for the controlled release of thiols, phenols, amines, sulfonamides or amides

“…The p K a value of sulfonamides, which is between 9 and 10, prevents their self-immolative release from molecular adaptors based on aza-quinone methide chemistry ( p -toluenesulfonamide 22, p K a ≂ 10.2). Consequently, the development of sulfonamide-modified prodrugs has been limited to molecules that can only temporarily improve the physicochemical properties by converting the sulphonamide into the corresponding N -acyloxyalkyl, 28 N -acyl, N -phthalyl 29 or N -phosphoramidic acid derivatives. 30 However, all these types of functional groups lead to products that are not particularly stable in physiological fluids and are not suitable for targeted or stimuli-sensitive delivery.…”