Cu(OTf)₂-mediated acylation and direct N-transacylation of sulfonamides

Abstract

Metal triflate-catalyzed acylation of sulfonamides and direct transacylation of N-acylsulfonamides have been investigated. The acylation of sulfonamides proceeds efficiently in the presence of a catalytic amount of Cu(OTf)₂ (0.001 equiv) using either carboxylic anhydrides or acyl chlorides as the acylating agents. Alternative catalysts suitable for this transformation include Al(OTf)₃, Fe(OTf)₃, Ga(OTf)₃, In(OTf)₃, and Er(OTf)₃. In the presence of Cu(OTf)₂ (0.2 equiv), N-acylsulfonamides undergo direct transacylation in excess acyl chlorides (10 equiv) to furnish new N-acylsulfonamides through exchange of N-acyl groups. Ga(OTf)₃, Fe(OTf)₃, and In(OTf)₃ are similarly reactive in catalyzing such transacylation transformations. The reaction conditions are mild and operationally convenient. A variety of functional groups including halogeno, keto, nitro, cyano, ether, and carboxylic ester are tolerated, providing the corresponding monoacylated N-acylsulfonamides in good to excellent yields.

GRAPHICAL ABSTRACT

KEYWORDS:

• Acylation
• direct transacylation
• N-acylsulfonamide
• Lewis acid
• cupric triflate

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Department of Science and Technology of Hubei Province [grant number 2023AFB1089] and the Hubei Provincial Key Laboratory of Drug Synthesis and Optimization [grant number ZD202303].