One‐Pot Bimetallic Pd/Cu‐Catalyzed Synthesis of Sulfonamides from Boronic Acids, DABSO and O‐Benzoyl Hydroxylamines

Abstract

A practical and straightforward bimetallic Pd/Cu catalytic system has been developed. This system affords various sulfonamides in one pot from easy-to-handle and readily available boronic acids, sulfur dioxide surrogate DABSO and O-benzoyl hydroxylamines in high yields. Without additional ligands, the newly developed catalytic system revealed a broad substrate scope for both partners and tolerated a wide array of functional groups even at low catalyst loadings. Furthermore, based on control experiments, a plausible mechanism has been proposed, in which sodium sulfinate has been isolated and identified as the crucial intermediate for this transformation.

Recent developments in palladium-catalyzed C–S bond formation

“…A gram-scale reaction for the preparation of diverse pesticides was performed under the standard conditions, showing potential capabilities in agriculture and industrial process. Importantly, this approach also provides a rapid and straightforward channel for the assembly of drug and biologically active molecules such as the marketed drug Vismodegib (83) and antiinflammatory drug Firocoxib (84) through the developed thiomethylation reaction and further derivatizations.…”

“…In further investigation of this type of sulfonylation process, Tu group also reported an elegant one-pot bimetallic Pd/Cu-catalyzed three-component cascade sulfonylation reaction (Scheme 47). 84 With DABSO as the ideal sulfur source, various substituted arylboronic acids (122) were treated with cyclic and acyclic O-benzoylhydroxylamines (123) using Pd/Cu as the co-catalysts, and a series of structurally diverse sulfonamides (124) were obtained in good to excellent yields without additional ligands. Mechanistically, the authors also performed some control experiments to gain further insights into this synthetic strategy.…”

Ligand‐Free Pd/Cu‐Catalyzed Aminosulfonylation of Aryl Iodides for Direct Sulfonamide Syntheses

“…By combining all of the aformentioned data and our previous study, [13,14] ap ossible mechanism was proposed (Scheme 4). Initially,t he Pd 0 species, generated in situ from Pd(OAc) 2 , [4,12] reacts with the aryl halides by oxidative addition to form Pd II intermediate A.S ubsequently, A undergoes the insertion of SO 2 to afford the Pd II species B.…”

“…[13] In combination with the ligand-free Pd-catalyzd sulfination of aryl boronic acids leading to sulfinates, [8] we have successfully extended this strategy to ab imetal-catalyzed sulfinationo fa ryl boronic acids leading to ad irect synthesis of sulfonamides with DABSOa nd O-benzoyl hydroxylamines in one pot (Scheme 1d). [14] It is noteworthy that Cu I active speciesg enerated from CuBr 2 in situ may be responsible for the electrophilic aminationo fs ulfinates.I nl ight of the two possible redox transformationsb etween Cu II/I and Pd 0/II involved, [15] we believed this ligand-free bimetal catalytic system may also be applied to the direct sulfonylation of aryl halides without the assistanceofligands and additional redox reagents.…”

“…In addition, other organic bases, including N,N-diisopropylethylamine (DIPEA), 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,4-diaza[2.2.2]bicyclooctane (DABCO) also resulted in decreasedy ields of product 3 (Table1,e ntries [11][12][13]. When other Pd II or Pd 0 precurors, including PdCl 2 ,P d(PhCN) 2 Cl 2 , [Pd(allyl)Cl] 2 and Pd 2 (dba) 3 were used, slightly lower yields were attained (Table 1, entries [14][15][16][17].…”