Generation of benzyne from aryl benziodoxaborole triflate under aqueous conditions and its reactions with alkyl aryl sulfides

Mesityl benziodoxaborole triflate is a unique benzyne precursor under aqueous conditions in the presence of NaHCO 3 at room temperature. Reactions of alkyl aryl sulfides with benzyne generated under these conditions selectively afford the corresponding sulfonium salts. In contrast, the previously reported reactions of alkyl aryl sulfides with common benzyne precursors under strongly basic anhydrous conditions lead to various products of cyclization, rearrangement


Introduction
In 1990, A. R. Katritzky and co-workers published a ground-breaking structural study on the cyclic structure of 2-iodosyl and 2-iodylbenzoic acids and their derivatives. 13][4][5] Structures of these compounds are characterized by the presence of a planar iodoxol ring with the I-O distance varying in a broad range: 2.18-2.55Å for cyclic and 2.55-3.00Å for pseudocyclic benziodoxoles. 5n the course of our search for new five-membered hypervalent iodine heterocycles, in 2017 we reported the preparation of pseudocyclic arylbenziodoxaboroles 3 in two steps from commercial 2iodoboronic acids 1 via acetoxybenziodoxaboroles 2 (Scheme 1).The pseudocyclic structure of arylbenziodoxaboroles with 2.69-2.71Å I-O bond distance was confirmed by single crystal X-ray analysis. 8urthermore, we have reported unique reactivity of arylbenziodoxaborole 3b as a benzyne precursor that can be triggered under neutral or slightly acidic conditions in aqueous solutions at room temperature. 8It should be noted that the previously known, common benzyne precursors, 9,10 such as: aryl halides, [11][12][13] arenediazonium-2-carboxylates, 14-16 1,2,3-benzothiadiazole 1,1-dioxides, 17 1-aminobenzotriazole, 18,19 ortho-silylaryl triflates (Kobayashi's reagent), 20 diaryliodonium salts, 21 and ortho-silyl phenyl iodonium triflate (Kitamura's reagent), 21,22 require activation by applying heat, irradiation, strong base (NaNH2, BuLi, RMgBr, LiHMDS, etc.), or the anhydrous fluoride anion, which is also a strong base and requires special handling to avoid moisture.In contrast, compound 3b can generate the corresponding aryne species by stirring its solution in a dichloromethane/water (9:1) mixture at room temperature. 8,23The generated in aqueous solution arynes can be effectively trapped in the presence of dienes, 8 azides, 8 or organic sulfides. 23We have also confirmed the formation of aryne from precursor 3b in these reactions by labelling and kinetics experiments. 23The nonfluorinated precursor 3a has demonstrated lower reactivity compared to 3b and required the presence of NaHCO3 to activate the reaction. 23heme 1. Preparation of pseudocyclic arylbenziodoxaboroles 3.
In the present paper, we describe the reactions of benzyne precursor 3a with organic sulfides triggered by water in the presence of NaHCO3 at room temperature and leading to selective formation of various sulfonium salts.This result is sharply different from the previously reported reactions of common benzyne precursors with organic sulfides under anhydrous basic conditions generally leading to various products of cyclization, rearrangement, or elimination but not to sulfonium salts. 24,25

Results and Discussion
Reagent 3a was prepared in gram-scale by a modified, combined procedure based on our previous works. 8,26cetoxybenziodoxaborole 2a was prepared by the hypochlorite oxidation in acetic acid (Scheme 1) and used without purification for conversion to mesityl benziodoxaborole triflate 3a by treatment with mesitylene in the presence of triflic acid (Scheme 1).Compound 3a was isolated in 80% overall yield after 2 steps as a stable colourless solid that can be stored for long time in a refrigerator in the absence of moisture.
We have investigated reactions of various alkyl aryl sulfides 4a-f with reagent 3a in a dichloromethane/water (9:1) mixture in the presence of NaHCO3 at room temperature.All reactions were complete in 3 hours and after simple work-up afforded analytically pure alkyl aryl sulfonium salts 5a-f in excellent yields (Scheme 2).The procedure worked well for the preparation of alkyl sulfonium salts from alkyl phenyl sulfides 4a-d with methyl, ethyl, isopropyl, and cyclopropyl groups, as well as from dibutyl sulfide 4e and tetrahydrothiophene 4f.Noteworthy, the reaction of ethyl phenyl sulfide 4b with aryne generated from reagent 3a in aqueous solution produced sulfonium salt 5b in 84% yield.For comparison, the previously reported similar reaction of ethyl phenyl sulfide with benzyne generated from benzenediazonium-2carboxylate under anhydrous conditions proceeded with elimination of ethylene leading to the corresponding diphenyl sulfide (Ph2S) in 92% yield. 27heme 2. Reactions of reagent 3a with organic sulfides.
It is important to note that the reactions of diphenyl sulfide 4g and dibenzothiophene 4h with reagent 3a at room temperature in aqueous solution afforded the corresponding triaryl sulfonium salts 5g and 5h.][30][31] Preparation of triaryl sulfonium salts in moderate yields using the Kobayashi aryne precursor in acetonitrile (25 °C, 36 h) in the presence of CsF under dry conditions has recently been reported. 32Based on the labeling experiments, the authors assumed that the molecule of acetonitrile acted as the source of protons in this reaction. 32he reactions of reagent 3a can be further extended to organic selenides.Reagent 3a reacts with diphenyl selenide 6 in CH2Cl2-H2O (9:1) in the presence of NaHCO3 to give the corresponding triphenyl selenonium salt 7 in good yield (Scheme 3).Previously reported synthesis of selenonium salt 7 required heating of diphenyl selenide with diphenyliodonium triflate in a chloroform solution in a thick-walled glass tube sealed with a Teflon screwcap maintained at 120 °C for 24 h. 30heme 3. Reaction of reagent 3a with diphenyl selenide.Based on our previously published studies, 8,23 we propose a two-step mechanism for the reactions of reagent 3a with organic sulfides and selenide (Scheme 4).At the first step, benzyne is generated by nucleophilic addition of a hydroxide anion (present in the aqueous solution of NaHCO3) to the boron atom of reagent 3a, followed by immediate elimination of boronic acid and mesityl iodide.Mesityl iodide (MesI), formed as a by-product in this step, was detected by NMR in the reaction mixture.This step is facilitated by the oxophilic character of the -B(OH)2 group and by the hypernucleofugic properties of the MesI + moiety in the iodonium salt 3a.At the second step, the addition of sulfide to the benzyne followed by protonation by water molecule gives the final product 5 or 7. Scheme 4. Mechanism of reactions of reagent 3a with organic sulfides and selenide.

Conclusions
In summary, we have demonstrated that mesityl benziodoxaborole triflate 3a is a unique benzyne precursor under aqueous conditions in the presence of NaHCO3 at room temperature.Reactions of alkyl aryl sulfides with benzyne generated under these conditions selectively afford the corresponding sulfonium salts, which is in contrast with the previously reported non-selective reactions of sulfides with common benzyne precursors under strongly basic anhydrous conditions.This very mild procedure works well for the preparation of sulfonium salts from alkyl aryl sulfides, diaryl sulfides, cyclopropyl phenyl sulfide, dialkyl sulfides, cyclic alkyl and arylsulfides, as well as selenonium salt from diphenyl selenide.

Experimental Section
General.All reactions were performed under dry argon atmosphere with flame-dried glassware.All commercial reagents were ACS reagent grade and used without further purification.Dichloromethane and acetonitrile were distilled from CaH2 immediately prior to use.Diethyl ether was distilled from Na/benzophenone.Melting points were determined in an open capillary tube with a Mel-temp II melting point apparatus.Infrared spectra were recorded as a KBr pellet on a Perkin-Elmer 1600 series FT-IR spectrophotometer. 1 H NMR, 13 C NMR, and 19 F NMR spectra were recorded on a Bruker 400 MHz or JEOL JNM-AL300 NMR spectrometers.Chemical shifts are reported in parts per million (ppm). 1 H and 13 C chemical shifts are referenced relative to tetramethylsilane.

Preparation of mesityl-1-phenyboronic acid-2-iodonium triflate (3a) from 2-iodophenylboronic acid 8,33
A solution of commercial 2-iodophenylboronic acid 1a (620 mg, 2.5 mmol) in acetic acid (6 mL) was cooled to 15 °C, and the commercial bleach solution (6.5 mL of ∼5% aqueous NaOCl) was added by small portions (about 0.1 mL each) under stirring.The stirring was continued at rt for overnight.After reaction, the colourless precipitate was filtered, washed with water, hexane, and ether, then dried in vacuum to afford 677.2 mg (89%) of 1-acetoxy-benziodoxaborole 2a, which was used in the next step without purification.The colourless solid was dissolved in dichloromethane (2.2 mL), cooled to 0 °C and TfOH (300.2 mg, 4.43 mmol) was added under stirring.The reaction mixture was stirred at 0 °C for 2 hours, then mesitylene (3.32 mL) was added to the reaction mixture, and stirring was continued overnight at room temperature.After reaction, the solvent was removed under reduced pressure to give an oily product, which was washed with diethyl ether several times then dried in vacuum to give mesityl-1-phenyboronic acid-2-iodonium triflate 3a, 1.037 g (80% yield; 2 steps), as a colourless solid (mp 160.8-164.3°C). 8