Unsymmetrical Disulfides Synthesis via Sulfenium Ion

Abstract

An umpolunga pproachf or the synthesis of unsymmetrical disulfides via sulfenium ion is reported.I ns itu generated electrophilic sulfeniumi on from electron-rich thiols reacted with second thiols to yield unsymmetrical disulfides. Using an iodine catalysta nd 4-dimethylaminopyridine (DMAP)/water as promoter,t he target syntheses were achieved in one pot under aerobic condition.Organicd isulfides are important functional moieties found in variousm arine natural products, [1] pharmaceuticals, [2] materials [3] and polymers. [4] Disulfides are also known for their odors especially in kitchen items, like in onions and garlics. [5] Pharmaceutically active disulfides are known to have anti-inflammatory, [6] antitumour, [7] antioxidants [8] and antiulcer [9] activities. Chemically,o rgano-disulfides are being used in catalyst, [10] in ligand designing, [11] towards producing fine chemicals andi n functional group protections. [12] In addition, the concept of constitutional dynamic chemistry (CDC) [13] and dynamic combinatorial chemistry (DCC) [14] is documented using the chemistry of disulfides. Due to the reversibility nature of the disulfide bond, formation of many products could be possible when more than one thiol building blocks present in equilibrium. [15] Therefore, it's always challengingt os ynthesize selectively any unsymmetrical disulfides from mixtureo ft hiols in one pot. [16] In Figure 1a,f ew examples of either pharmaceutically important or naturallyo ccurring molecules containing disulfides functionalities are shown. [16b] The known approaches for the synthesis of disulfides are mainly based on using molecular oxygen, [17] transition metals, [18] phosphine-free cationic rhodium(I) complex catalyst, [19] Cu I -phenanthroline catalyst, [20] base catalyzed, [21] non-transition metals, [22] oxidants, [23] sodium perborate, [24] metal organicf rame works (MOFs), [25] microwavea ssisted, [26] electrochemical methods, [27] etc. Recently Dethe and co-workersd eveloped synthesis of unsymmetrical disulfides using fac-Ir(ppy) 3 as photocatalyst and visible light from white LED (Figure 1b). [28] Similarly,u nsymmetrical disulfide synthesis is also reported using O 2 as the oxidant and cobalt(II)phthalocyanine-tetra-sodium sulfonate as the catalyst (Figure 1b). [29] Herein, we reporto ne pot synthesis of unsymmetrical organodisulfides ( Figure 1c)v ia umpolung approach in ethanol sol-

1,3‐Diisopropylcarbodiimide‐Mediated Synthesis of Disulfides from Thiols

“…After stirring for 6 h at that temperature (Figure C), the conversion was essentially complete, and a novel by‐product containing the i Pr‐NH moiety was observed at 5.51 (br d, J =7.7 Hz), 3.64 (dp, J 1 =7.6 Hz, J 2 =6.4 Hz) and 1.00 (d, J =6.4 Hz) ppm that accounted for nearly 70 % of the i Pr by integration area. This by‐product was identified as diisopropylurea 9 …”

An Overview of Recent Advances in the Synthesis of Organic Unsymmetrical Disulfides

“…Mal and coworkers described the synthesis of unsymmetrical disulfides through sulfenium ion by aerobic oxidation using iodine as a catalyst and DMAP/Water as a promoter ( Scheme 48). [61] The unsymmetrical diaryl disulfides were obtained in good to excellent yields and only a small amount of symmetrical disulfide was detected. The symmetrical disulfides were observed as the major product in the absence of DMAP.…”

Noncovalent Interactions in C–S Bond Formation Reactions

“…39 Thus, as expected, iodine reagents can also form a CT complex with aryl thiols for the generation of sulfenium ions. 40 1.8.1. Iodine(III) in Aromatic C−H Sulfenylation.…”

“…Acidic iodine reagents form a strong CT complex with the basic amines . Thus, as expected, iodine reagents can also form a CT complex with aryl thiols for the generation of sulfenium ions …”