University of Huddersfield Repository Aqueous DMSO Mediated Conversion of (2-(Arylsulfonyl)vinyl)iodonium Salts to Aldehydes and Vinyl Chlorides

: Vinyl(aryl)iodonium salts are useful compounds in organic synthesis but they are under-utilized and their chemistry is under-developed. Herein is described the solvolysis of some vinyl(phenyl)iodonium salts, bearing an arylsulfonyl group, in aqueous DMSO leading to aldehyde formation. This unusual process is selective and operates under ambient conditions. Furthermore, the addition of aqueous HCl and DMSO to these vinyl(aryl)iodonium salts allows their facile conversion to vinyl chlorides.


Introduction
Hypervalent iodine chemistry has received considerable attention in recent years, particularly in the area of small molecule synthesis [1][2][3]. Reasons for this include the ease-of-use of hypervalent iodine reagents, their low toxicity and the ability to effect useful, novel synthetic transformations.
Iodonium salts are iodine(III) species (also known as λ 3 -iodanes) with two carbon ligands and one non-carbon ligand [4]. These compounds are of increasing importance in synthesis, however, the majority of reported research in this area deals with the utility of diaryliodonium salts [5]. Alkenyl(aryl)iodonium salts are also useful reagents in synthesis, but their chemistry is relatively underdeveloped [6,7].
One particular reaction of alkenyl(aryl)iodonium salts is solvolysis which has been shown to occur in protic solvents such as methanol [19]. Typically, primary vinylic substrates require elevated temperatures for complete conversion and several products are formed. For example, heating (Z)-2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborate 1 in methanol at 60 • C leads to the formation of three products in approximately equal yields (Scheme 1). Deuterium labelling studies suggest that this process proceeds through phenyl-assisted loss of iodobenzene followed by addition of solvent, 1,2-migration or loss of a proton. Further work demonstrated that the outcome of this solvolysis process is dependent on the structure of the iodonium salt and the solvent used. Scheme 1. Solvolysis of (Z)-2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborate 1 with MeOH at 60 °C.
Hinkle and co-workers studied the fragmentation of similar β,β-disubstituted alkenyl(aryl)iodonium triflates in methanol solution and observed similar results to the tetrafluoroborate salts [20]. They also observed decomposition of the iodonium triflates upon standing in CDCl3 at room temperature over several hours. Okuyama and Ochiai reported the acetolysis of (E)-styryl-and (E)-1-decenyl(phenyl) iodonium tetrafluoroborate at elevated temperature [21].
Another process that alkenyl(aryl)iodonium salts have been shown to undergo is conversion to vinyl halides upon treatment with tetrabutylammonium halide in dichloromethane [22]. This transformation proceeds with retention of configuration.
During our studies on β-sulfone substituted alkenyl(phenyl)iodonium salts we noticed that upon standing in wet deuterated DMSO, the water was slowly consumed and the iodonium salt was converted into a new chemical entity. We decided to investigate this process.

Results and Discussion
We initiated our study with the preparation of a range of alkynyl(phenyl)iodonium trifluoroacetates 2, which were prepared in one step from the terminal acetylenes following Carroll's method (Scheme 2) [23]. High yields were obtained in all cases and recrystallization provided analytically pure samples, apart from 2e which appeared to be somewhat unstable. 2e was taken forward to the next step immediately before further decomposition could occur. Scheme 2. Preparation of alkynyl(phenyl)iodonium trifluoroacetates 2. Scheme 1. Solvolysis of (Z)-2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborate 1 with MeOH at 60 • C.
Hinkle and co-workers studied the fragmentation of similar β,β-disubstituted alkenyl(aryl) iodonium triflates in methanol solution and observed similar results to the tetrafluoroborate salts [20]. They also observed decomposition of the iodonium triflates upon standing in CDCl 3 at room temperature over several hours. Okuyama and Ochiai reported the acetolysis of (E)-styryl-and (E)-1-decenyl(phenyl)iodonium tetrafluoroborate at elevated temperature [21].
Another process that alkenyl(aryl)iodonium salts have been shown to undergo is conversion to vinyl halides upon treatment with tetrabutylammonium halide in dichloromethane [22]. This transformation proceeds with retention of configuration.
During our studies on β-sulfone substituted alkenyl(phenyl)iodonium salts we noticed that upon standing in wet deuterated DMSO, the water was slowly consumed and the iodonium salt was converted into a new chemical entity. We decided to investigate this process.

Results and Discussion
We initiated our study with the preparation of a range of alkynyl(phenyl)iodonium trifluoroacetates 2, which were prepared in one step from the terminal acetylenes following Carroll's method (Scheme 2) [23]. High yields were obtained in all cases and recrystallization provided analytically pure samples, apart from 2e which appeared to be somewhat unstable. 2e was taken forward to the next step immediately before further decomposition could occur. Scheme 1. Solvolysis of (Z)-2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborate 1 with MeOH at 60 °C.
Hinkle and co-workers studied the fragmentation of similar β,β-disubstituted alkenyl(aryl)iodonium triflates in methanol solution and observed similar results to the tetrafluoroborate salts [20]. They also observed decomposition of the iodonium triflates upon standing in CDCl3 at room temperature over several hours. Okuyama and Ochiai reported the acetolysis of (E)-styryl-and (E)-1-decenyl(phenyl) iodonium tetrafluoroborate at elevated temperature [21].
Another process that alkenyl(aryl)iodonium salts have been shown to undergo is conversion to vinyl halides upon treatment with tetrabutylammonium halide in dichloromethane [22]. This transformation proceeds with retention of configuration.
During our studies on β-sulfone substituted alkenyl(phenyl)iodonium salts we noticed that upon standing in wet deuterated DMSO, the water was slowly consumed and the iodonium salt was converted into a new chemical entity. We decided to investigate this process.

Results and Discussion
We initiated our study with the preparation of a range of alkynyl(phenyl)iodonium trifluoroacetates 2, which were prepared in one step from the terminal acetylenes following Carroll's method (Scheme 2) [23]. High yields were obtained in all cases and recrystallization provided analytically pure samples, apart from 2e which appeared to be somewhat unstable. 2e was taken forward to the next step immediately before further decomposition could occur. These alkynyl(phenyl)iodonium trifluoroacetates 2 were converted into a small family of alkenyl(phenyl)iodonium tetrafluoroborates 3 by mixing with aryl sulfinic acids in methanol (Scheme 3). As expected, only one isomer of product was formed in these reactions. These iodonium salts are completely stable in CDCl 3 unlike those in Hinkle's study [14]; possibly due to a stabilizing interaction between the sulfone oxygen and the iodine(III) center. With these compounds in hand, their reactivity in DMSO was investigated.
These alkynyl(phenyl)iodonium trifluoroacetates 2 were converted into a small family of alkenyl(phenyl)iodonium tetrafluoroborates 3 by mixing with aryl sulfinic acids in methanol (Scheme 3). As expected, only one isomer of product was formed in these reactions. These iodonium salts are completely stable in CDCl3 unlike those in Hinkle's study [14]; possibly due to a stabilizing interaction between the sulfone oxygen and the iodine(III) center. With these compounds in hand, their reactivity in DMSO was investigated. Iodonium salt 3aa was dissolved in anhydrous DMSO and no observable change occurred after stirring overnight at room temperature (Table 1). However, when water was added to the solution the iodonium salt was slowly consumed and aldehyde 4aa was formed along with unknown compounds in ratios that changed with each repetition (entry 2). We varied the solvent but no conversion of 3aa occurred in all cases (entries 3-6). We avoided the use of alcohol solvents because of the previous studies highlighted above. Returning to the use of DMSO as solvent, we hypothesized that acidic or basic conditions could have an effect on this process. In the event, the addition of 2 M NaOH solution provided clean access to aldehyde 4aa (entry 7). Subsequently, we found that simply shaking the reaction mixture with added water containing the aldehyde and unknown compounds led to complete conversion to the aldehyde 4aa (entry 8). Presumably, the unknown compounds are intermediates en route to 4aa and the increased agitation completes the solvolysis process. Performing the reaction with added hydrochloric acid led to complete conversion to the vinyl chloride 5aa with retention of stereochemistry (entry 9).
The scope of this solvolysis reaction was investigated and aldehydes 4 were immediately reduced to the alcohols 6 to facilitate isolation of analytically pure compounds (Scheme 4). In all cases, yields of 60%-70% were obtained for the two steps. The tetrafluoroborate counterion is not critical to this process as the triflate analog of 3aa underwent similarly facile hydrolysis. However, (E)-phenyl(styryl)-and (E)-1-octen-1-yl(phenyl)iodonium tetrafluoroborate, vinyliodonium salts lacking the β-sulfone moiety, were stable under these conditions and were returned unchanged.

Scheme 3. Preparation of alkenyl(phenyl)iodonium tetrafluoroborates 3.
Iodonium salt 3aa was dissolved in anhydrous DMSO and no observable change occurred after stirring overnight at room temperature (Table 1). However, when water was added to the solution the iodonium salt was slowly consumed and aldehyde 4aa was formed along with unknown compounds in ratios that changed with each repetition (entry 2). We varied the solvent but no conversion of 3aa occurred in all cases (entries 3-6). We avoided the use of alcohol solvents because of the previous studies highlighted above. Returning to the use of DMSO as solvent, we hypothesized that acidic or basic conditions could have an effect on this process. In the event, the addition of 2 M NaOH solution provided clean access to aldehyde 4aa (entry 7). Subsequently, we found that simply shaking the reaction mixture with added water containing the aldehyde and unknown compounds led to complete conversion to the aldehyde 4aa (entry 8). Presumably, the unknown compounds are intermediates en route to 4aa and the increased agitation completes the solvolysis process. Performing the reaction with added hydrochloric acid led to complete conversion to the vinyl chloride 5aa with retention of stereochemistry (entry 9).
The scope of this solvolysis reaction was investigated and aldehydes 4 were immediately reduced to the alcohols 6 to facilitate isolation of analytically pure compounds (Scheme 4). In all cases, yields of 60%-70% were obtained for the two steps. The tetrafluoroborate counterion is not critical to this process as the triflate analog of 3aa underwent similarly facile hydrolysis. However, (E)-phenyl(styryl)and (E)-1-octen-1-yl(phenyl)iodonium tetrafluoroborate, vinyliodonium salts lacking the β-sulfone moiety, were stable under these conditions and were returned unchanged.   The conversion of the iodonium salts 3 to vinyl chlorides 5 was investigated next and excellent yields were obtained in all cases (Scheme 5). Remarkably, this functional group conversion was complete within 15 min at room temperature. But again, (E)-phenyl(styryl)-and (E)-1-octen-1-yl(phenyl)iodonium tetrafluoroborate, vinyliodonium salts lacking the β-sulfone moiety, were stable under these conditions and were returned unchanged. As detailed above, this transformation has already been demonstrated using alternative conditions but we wished to determine whether DMSO was critical in our case (as with the aldehyde conversion). In the event, attempting the chlorination with 2 M HCl in a range of solvents, including dichloromethane, ethyl acetate, nitromethane, diethyl ether and acetonitrile, led to low conversions (5%-40%) in all cases after stirring overnight.   The conversion of the iodonium salts 3 to vinyl chlorides 5 was investigated next and excellent yields were obtained in all cases (Scheme 5). Remarkably, this functional group conversion was complete within 15 min at room temperature. But again, (E)-phenyl(styryl)-and (E)-1-octen-1-yl(phenyl)iodonium tetrafluoroborate, vinyliodonium salts lacking the β-sulfone moiety, were stable under these conditions and were returned unchanged. As detailed above, this transformation has already been demonstrated using alternative conditions but we wished to determine whether DMSO was critical in our case (as with the aldehyde conversion). In the event, attempting the chlorination with 2 M HCl in a range of solvents, including dichloromethane, ethyl acetate, nitromethane, diethyl ether and acetonitrile, led to low conversions (5%-40%) in all cases after stirring overnight. The conversion of the iodonium salts 3 to vinyl chlorides 5 was investigated next and excellent yields were obtained in all cases (Scheme 5). Remarkably, this functional group conversion was complete within 15 min at room temperature. But again, (E)-phenyl(styryl)-and (E)-1-octen-1-yl(phenyl)iodonium tetrafluoroborate, vinyliodonium salts lacking the β-sulfone moiety, were stable under these conditions and were returned unchanged. As detailed above, this transformation has already been demonstrated using alternative conditions but we wished to determine whether DMSO was critical in our case (as with the aldehyde conversion). In the event, attempting the chlorination with 2 M HCl in a range of solvents, including dichloromethane, ethyl acetate, nitromethane, diethyl ether and acetonitrile, led to low conversions (5%-40%) in all cases after stirring overnight. It is clear that DMSO has properties that aid the degradation of vinyliodonium salts and care should be taken that perfectly anhydrous solvent is used when this phenomenon is not desirable.
In summary, the solvolysis of alkenyl(phenyl)iodonium tetrafluoroborates containing a β-sulfone moiety occurs readily in aqueous DMSO solution at room temperature leading to selective aldehyde formation. Furthermore, the addition of aqueous HCl to the DMSO solution allows rapid vinyl chloride formation. This particular decomposition of vinyliodonium salts is unprecedented and demonstrates the unique properties of DMSO as a solvent.

General Information
All commercially available materials were used as received. 1 H-NMR spectra were recorded at 400 MHz and 13 C-NMR spectra at 100 MHz. IR spectra were recorded with neat samples and signals are labelled as strong (s), medium (m) or weak (w). HRMS were recorded in ESI mode and only molecular masses are reported. 2a and 2b were prepared according to the method of Carroll and co-workers and the data matched the literature values [23]. 3aa was prepared following Ochiai's protocol [14]. 6aa and 6ab are known compounds [24].

General Procedure for Alkynyl(phenyl)iodonium Trifluoroacetate 2 Formation: Preparation of ((4-Ethylphenyl)ethynyl)(phenyl)iodonium 2,2,2-trifluoroacetate 2c
Following Carroll's procedure [23], trifluoroacetic acid (1.4 mL, 19 mmol, 2 equiv.) was added dropwise to a stirred solution of diacetoxyiodobenzene (3 g, 9.3 mmol, 1 equiv.) in CH2Cl2 (60 mL) at −30 °C. The mixture was stirred for 30 min, then warmed to room temperature and stirred for a further hour. 1-Ethyl-4-ethynyl benzene (1.3 mL, 9.3 mmol, 1 equiv.) was added dropwise and the resulting mixture was stirred in darkness at room temperature for 3.5 h. The solution was concentrated in vacuo to around 30 mL then diethyl ether (20 mL) and petroleum ether (40 mL) were added which initiated crystallization of the product. After cooling in a freezer (−20 °C) for 48 h, the solid was filtered and dried in vacuo to provide 2c as a white crystalline solid It is clear that DMSO has properties that aid the degradation of vinyliodonium salts and care should be taken that perfectly anhydrous solvent is used when this phenomenon is not desirable.
In summary, the solvolysis of alkenyl(phenyl)iodonium tetrafluoroborates containing a β-sulfone moiety occurs readily in aqueous DMSO solution at room temperature leading to selective aldehyde formation. Furthermore, the addition of aqueous HCl to the DMSO solution allows rapid vinyl chloride formation. This particular decomposition of vinyliodonium salts is unprecedented and demonstrates the unique properties of DMSO as a solvent.

General Information
All commercially available materials were used as received. 1 H-NMR spectra were recorded at 400 MHz and 13 C-NMR spectra at 100 MHz. IR spectra were recorded with neat samples and signals are labelled as strong (s), medium (m) or weak (w). HRMS were recorded in ESI mode and only molecular masses are reported. 2a and 2b were prepared according to the method of Carroll and co-workers and the data matched the literature values [23]. 3aa was prepared following Ochiai's protocol [14]. 6aa and 6ab are known compounds [24].

General Procedure for Alkenyl(phenyl)iodonium Tetrafluoroborate 3 Formation: Preparation of (Z)-Phenyl(2-phenyl-2-tosylvinyl)iodonium Tetrafluoroborate, 3ab
Following Ochiai's procedure [14], phenyl(phenylethynyl)iodonium trifluoroacetate (0.50 g, 1.2 mmol, 1 equiv.) dissolved in MeOH (5 mL) was added to a solution of 4-methylbenzene sulfinic acid (0.20 g, 1.3 mmol, 1.1 equiv.) in MeOH (2 mL) at 0 • C under a N 2 atmosphere. The reaction mixture was stirred for 45 min then poured into saturated aqueous sodium tetrafluoroborate solution (5 mL). A white precipitate was formed which was filtered off and washed with CH 2 Cl 2 (2 × 8 mL). The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was a clear, colourless, viscous oil. A 1:1 mixture of diethyl ether and petroleum ether (5 + 5 mL) was added to the residue, then the mixture was swirled and the solvent removed by decantation. This was repeated until a white solid was formed. This crude product was recrystallized from the minimum amount of CH 2   (Z)-Phenyl(2-phenyl-2-(phenylsulfonyl)vinyl)iodonium tetrafluoroborate, 3aa (50 mg, 0.094 mmol, 1 equiv.) was dissolved in DMSO (0.5 mL) at room temperature. Deionized water (20 µL) was added and the mixture was stirred overnight. Water (2.5 mL) was added to the mixture and the solution was shaken and then extracted with ethyl acetate (2 × 5 mL). The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under vacuum. The crude product was dissolved in methanol (2 mL) and LiBH 4 (2 mg, 0.094 mmol, 1 equiv.) was added in one portion. The mixture was stirred overnight and then extracted with diethyl ether (2 × 5 mL) and washed with water (5 mL). (Z)-Phenyl(2-phenyl-2-(phenylsulfonyl)vinyl)iodonium tetrafluoroborate 3aa (0.050 g, 0.094 mmol) was dissolved in DMSO (0.5 mL) at room temperature. HCl (2 N, 50 µL) was added and the mixture was stirred for 15 min. Brine (5 mL) was added to the mixture and the solution was shaken. This was extracted with ethyl acetate (2 × 10 mL) and washed with water (5 mL). The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under vacuum.