Synthesis of Thiosulfonates via CuI‐Catalyzed Reductive Coupling of Arenesulfonyl Chlorides Using Na₂SO₃ or NaHSO₃ as Reductants

Abstract

Am ild and efficient methodf or the synthesis of thiosulfonates has been developed through aC uI-catalyzed reductivec oupling of arenesulfonyl chlorides using Na 2 SO 3 or NaHSO 3 as the terminal reductantu nder an itrogen atmosphere at room temperature. Ab road scope of thiosulfonates was obtained in high to excellent yields via this simple, practical and economical transformation.T he ease of handling, the use of low-costa nd readily available reaction materials at room temperature,a nd the efficiency on al arge scale, make this method attractive in both organic synthesis and industrial applications.Thiosulfonate derivatives have shown ab road spectrum of biological activities [1] and widespreada pplications in both polymer production and photographic processes. [2] Furthermore, they are powerful sulfenylating agentsi ns ynthetic organic chemistry. [3] As sulfenylating agents, they are more stable and easier to handle than sulfinyl chlorides, and reactf aster and are more efficient than disulfides. Although the synthetic importanceo ft hiosulfonates is known,t hey have not been extensively applied in organic synthesis and have been seldom used in industrial processes as sulfenylating agentsb ecause there had not been very economical and practical methods for synthesizing them.Many synthetic chemists devoted continuous efforts to explore synthetic strategies for the preparation of thiosulfonates, therefore an umber of methods have been established (Scheme 1). These included:( i) the direct oxidation of thiols or disulfides, [4] (ii)the coupling of disulfides or thiols with sodium sulfonate, [5,6] (iii)the reduction of sulfonyl chlorides, [7,8] and (iv) the reactiono fs ulfonyl halides with other thiols or thiolates. [9] Sulfonylc hlorides are an important class of organic compounds that have long been used as inexpensive and commercially available startingm aterials in organic synthesis, materials science, and medicinal chemistry. [10] Severale ffective methodsh ave been developed for the synthesis of symmetrical thiosulfonates by reducing sulfonyl chlorides with N,N-dimethyl hydrazine, [7a] potassium iodide in anhydrous acetone/ pyridine, [7b] acetyl-chloride-activated zinc, [7c] samarium powder in DMF, [7d] and tetrabutylammoniumi odide. [8] Although these strategies provided useful accesst os ubstituted symmetrical thiosulfonates, there are noticeable drawbacks associated with them, such as relatively strict andh arsh reactionc onditions, expensive and sensitive reductants,e xcessive requirementsf or acid or base additives and tediousw ork-up procedures. In the case of reactions involving reductantsa nd bases, such as the KI/acetone/pyridine system, anhydrous acetone, as well as large quantities of the KI reductant and pyridine, are needed, with the latter requiring 2.5 equiv (1 mL, 12.5 mmol) rather than ac atalytic amount, as reported in literature. [7b] Owing to the toxicityo fp yridine, its use as ab ase is no longerf avored in organic synthesis. Therefore, the development of mild, economic,env...

Synthesis of Symmetrical and Unsymmetrical Thiosulfonates from Disulfides through Electrochemically Induced Disulfide Bond Metathesis and Site‐Selective Oxidation

“…Due to the significance of this substance class, many synthetic strategies have been developed during the past decades [15] . Symmetrical thiosulfonates can be prepared by oxidative dimerization of thiols, [16–21] oxidation of disulfides, [16,22–26] reduction of sulfonyl chlorides [27–32] or the decomposition of sulfonyl hydrazines [22,33,34] . The generation of unsymmetrical thiosulfonates is more challenging and can be accomplished for example by cross‐coupling of sodium sulfinates with thiols, [35,36] disulfides [37–40] or N ‐arylthiosuccinimides [41,42] .…”

Nickel-Catalyzed Difunctionalization of Alkynyl Bromides with Thiosulfonates and N-Arylthio Succinimides: A Convenient Synthesis of 1,2-Thiosulfonylethenes and 1,1-Dithioethenes

“…In accordance to known procedure the S-phenyl benzenesulfonothioate (2a) [6] was prepared by oxidation of corresponding diaryl disulfides. The symmetrical thiosulfonates (2bf,n) [7] were prepared from corresponding sulfonyl chlorides using known procedure. The unsymmetrical thiosulfonates (2g-l) [8] were prepared from corresponding diaryl disulfides with sodium sulfinate salts using reported procedure.…”

“…Organosulfur compounds 5 containing sulfone and thioether are attractive functional groups in organic synthesis 6 as well as pharmaceutical interest. 7 Recently, thiosulfonates (RS-SO2R 1 ) [8][9][10] have been revolutionized to install two distinct C S bonds Scheme 1. Representative vicinal thiosulfonylation through atom transfer radical addition (ATRA).…”

“…The use of 5 mol% of NiCl2.6H2O afforded the thiosulfonylated product 3aa in 81% yield with excellent stereoselectivity (entry 6). Inspired by these results, we have screened various Nicatalysts that were not beneficial to improve the yield (entries [7][8][9][10]. Lowering the amount of Cs2CO3 or elevated temperature or under aerobic conditions were unsuccessful to give a better outcome (entries [11][12][13].…”

Temperature‐Controlled Chemoselective Synthesis of Thiosulfonates and Thiocyanates: Novel Reactivity of KXCN (X=S, Se) towards Organosulfonyl Chlorides

“…In 2016, Huang delineated the reduction of sulfonyl chlorides with tetrabutylammonium iodide in acetonitrile/acetone (5 : 1) at room temperature [9a] . In 2017, Zhang reported the synthesis of thiosulfonates through CuI‐catalyzed reductive coupling of arenesulfonyl chlorides using Na 2 SO 3 or NaHSO 3 as the reductant [10] …”