FULL PAPER DOI: 10.1002/ejoc.201403531 Iodine-Catalyzed Oxidative Amination of Sodium Sulfinates: A Convenient Approach to the Synthesis of Sulfonamides under Mild Conditions Chonchanok Buathongjan, [a] Danupat Beukeaw, [a,b] and Sirilata Yotphan* [a,b] Keywords: Iodine / Sulfonamides / Sodium sulfinates / Amines / Oxidative amination The iodine-catalyzed oxidative amination of sodium sulfin- ates in the presence of sodium percarbonate as the oxidant has been developed. The reaction shows good substrate scope and tolerates a wide range of functionalities in both amine and sodium sulfinate substrates. Aliphatic amines, heteroaromatic amines and hydrochloride salts of amines can Introduction Sulfonamides are a privileged class of pharmaceutical compounds with a broad spectrum of activities. [1] They are employed widely in medicinal chemistry as essential struc- tural motifs for the development of new therapeutic agents. Sulfonamide drugs have various clinical applications, in- cluding as antibacterials, diuretics, anticonvulsants, and HIV protease inhibitors. [2] Examples of important sulfon- amide drugs are azosemide (diureatic), piroxicam (anti-in- flammatory drug), sumatriptan (anti-migraine agent), and amprenavir (protease inhibitor for treatment of HIV infec- tion). Other applications of sulfonamides include their use as nitrogen protecting groups and incorporation into or- ganic dyes to improve stability and lubrication. [3] Because of their significance, a number of advancements in sulfon- amide synthesis have been developed, in order to provide the sulfonamide products in decent yields and with high selectivity and good functional group compatibility. [4] Ex- amples of effective methods for sulfonamide formation in- clude the traditional synthesis from sulfonyl chlorides and amino compounds, [5] catalytic cross-coupling of sulfon- amides with halides, [6] oxidation of sulfinamides, [7] and aminosulfonation of hydrocarbons. [8] Despite their poten- [a] Center of Excellence for Innovation in Chemistry (PERCH-CIC), Department of Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand http://www.perch-cic.org/index.php [b] Center of Catalysis, Department of Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand E-mail: sirilata.yot@mahidol.ac.th http://chemistry.sc.mahidol.ac.th/en Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201403531. Eur. J. Org. Chem. 2015, 1575–1582 © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1575 be employed as the amine sources in this transformation. Mechanistic studies indicated that a radical pathway might be involved in the reaction process. This transition-metal- free protocol offers an alternative and convenient approach for a preparation of a series of sulfonamides in moderate to good yields under mild conditions. tial utility, many of these methods have some limitations such as vigorous conditions, side reactions, tedious isolation procedures, poor functional group tolerance, difficulty in handling, and problems with long-term storage. Recently, Jiang and co-workers reported a new route to sulfonamide synthesis through Cu-catalyzed oxidative cou- pling of amines and the bench-stable, nonhygroscopic so- dium sulfinates. [9,10] This study offered a method for the preparation of sulfonamides in good yields and with excel- lent chemoselectivity; however, a high temperature is re- quired to facilitate product formation. Inspired by this work, we became interested in exploring the possibility of replacing the copper catalyst by employing the transition- metal-free catalyzed oxidative coupling strategy. In particu- lar, catalysis involving molecular iodine (I 2 ) and its salts attracted our attention, due to the ease of handling, low toxicity, commercial availability, and mild reactivity of the reagents. A number of recent studies have demonstrated the utility of iodine catalysis as an efficient and powerful tool for formation of carbon–carbon and carbon–heteroatom bonds. [11] The combination of catalytic amounts of iodine or iodide salts and oxidants such as tert-butyl hydroperox- ide (TBHP) or hydrogen peroxide (H 2 O 2 ) has proven to provide versatile oxidation conditions for many oxidative coupling transformations. [12] Herein we report a method for the formation of sulfon- amides by I 2 -catalyzed oxidative amination of sodium sulfi- nates. Readily available sodium percarbonate – Na 2 CO 3 · 1.5 H 2 O 2 , a solid carrier of hydrogen peroxide [13] – is an effective oxidant for this transformation. Our approach has several advantages, including being transition-metal-free, using bench-stable reagents, involving simple handling un- der mild and air-stable conditions, accommodating a broad scope of substrates, and avoiding the generation of toxic byproducts.