Sulfonylimino Group Transfer Reaction Using Imino-λ3-iodanes with I2 as Catalyst Under Metal-free Conditions

A new practical procedure of imination for sulfide has been developed. The treatment of (N-tosylimino)-phenyl-λ3-iodane, PhINTs, with various sulfides in the presence of a catalytic amount of I2 under metal-free conditions affords the corresponding N-tosylsulfilimine compounds with moderate to good yields. This facile transfer procedure of the sulfonylimino group can also be applied to triphenylphosphine to produce the respective iminotriphenylphosphoranes in high yields. According to the reaction mechanism studies, the process of imination from (N-tosylimino)-phenyl-λ3-iodane to sulfide under the conditions may involve radical steps within the reaction mechanism.

Organohypervalent iodine compounds are known as efficient oxidative reagents for organic synthesis because of the exceptionally high leaving ability of the iodobenzene group [20][21][22][23][24]. The versatile reactivity of hypervalent iodine(III) compounds allows for various bond formations, some of which are otherwise difficult reactions in the absence of iodine(III) reagents. Particularly, N-sulfonylimino-λ 3 -iodanes represent an important class of hypervalent iodine(III) compounds, which are commonly used as N-sulfonylimino group sources or selective oxidative reagents for various organic substrates [25][26][27]. For example, the reaction of sulfides with (N-tosylimino)-phenyl-λ 3 -iodane in the presence of Cu, Mn, or Fe metal catalyst gave the corresponding sulfoximine compounds (Scheme 1a) [28][29][30][31][32][33]. However, a metal-free condition for reactions is a significant goal in the development of eco-friendly reaction methodology. Recently, Lamar and Nicholas reported the C-H amidation reaction of saturated or unsaturated hydrocarbons using imino-λ 3 -iodanes in the presence of a catalytic amount of elemental iodine under transition metal-free conditions [34]. Lamar's group also reported the imidation reaction of aldehydes under similar reaction conditions [35]. Metal-free aziridination reactions of styrenes using (N-tosylimino)-phenyl-λ 3 -iodane in the presence of I 2 -tetrabutylammonium iodide combination have been developed by Minakata and co-worker [36]. To the best of our knowledge, however, I 2 mediated metal-free imination reactions of sulfides using imino-λ 3 -iodanes have not been developed. In this paper, we report the sulfonylimino group transfer reaction from imino-λ 3 -iodane to sulfide atom under metal-free conditions (Scheme 1b). Reaction mechanisms of this sulfonylimino group transfer reaction may involve the radical process under reaction conditions.
Molecules 2018, 23, x FOR PEER REVIEW 2 of 12 organic substrates [25][26][27]. For example, the reaction of sulfides with (N-tosylimino)-phenyl- 3iodane in the presence of Cu, Mn, or Fe metal catalyst gave the corresponding sulfoximine compounds (Scheme 1a) [28][29][30][31][32][33]. However, a metal-free condition for reactions is a significant goal in the development of eco-friendly reaction methodology. Recently, Lamar and Nicholas reported the C-H amidation reaction of saturated or unsaturated hydrocarbons using imino- 3 -iodanes in the presence of a catalytic amount of elemental iodine under transition metal-free conditions [34].
Lamar's group also reported the imidation reaction of aldehydes under similar reaction conditions [35]. Metal-free aziridination reactions of styrenes using (N-tosylimino)-phenyl- 3 -iodane in the presence of I2-tetrabutylammonium iodide combination have been developed by Minakata and coworker [36]. To the best of our knowledge, however, I2 mediated metal-free imination reactions of sulfides using imino- 3 -iodanes have not been developed. In this paper, we report the sulfonylimino group transfer reaction from imino- 3 -iodane to sulfide atom under metal-free conditions (Scheme 1b). Reaction mechanisms of this sulfonylimino group transfer reaction may involve the radical process under reaction conditions. Scheme 1. Transfer reaction of sulfonylimino groups from imino- 3 -iodane to sulfide atom. (a) Metalcatalyzed imidation reaction of sulfides, (b) Metal-free imidation reaction of sulfides.

Optimization of Reaction Conditions
Our approach to metal-free sulfonylimino group transfer reaction is based on previously reported reaction conditions such as (N-tosylimino)-phenyl- 3 -iodane in the presence of I2 as a catalyst [34,36]. In the initial experiment, we investigated the reaction of thioanisole 1a (1 equiv.) with (N-tosylimino)-phenyl- 3 -iodane 2a (1.2 equiv.) in the presence of a catalytic amount of both I2 and tetrabutylammonium iodide (TBAI) as an additive under various solvents at room temperature ( Table 1, entries 1-9). We have found that dichloromethane is an efficient solvent for the metal-free imination reaction of thioanisole 1a using (N-tosylimino)-phenyl- 3 -iodane 2a. The presence of TBAI as an additive did not affect this reaction (entry 10). However, in the absence of I2 as a catalyst, the reaction dramatically changed, resulting in a low yield of the formation of the desired N-tosyl sulfilimine 3a (entries 11 and 12). Extension of the reaction time was effective for the desired product 3a yield (entry 14). Decreasing the amount of I2 catalyst from 10 mol% to 2 mol% increased the yield of N-tosyl sulfilimine 3a (entries [14][15][16]. These results implied that the slow generation of the activated species was very important for this reaction because the species generated from (Ntosylimino)-phenyl- 3 -iodane 2a and I2 were probably unstable in the reaction mixtures. Meanwhile, further reduction of the amount of I2 catalyst and a longer reaction time led to a decreased amount of the desired product 3a (entries 17 and 18). Finally, performing the reaction under the dark conditions slightly suppressed the product yield, which supports a radical pathway in the reaction mixtures (entry 19) [36].

Optimization of Reaction Conditions
Our approach to metal-free sulfonylimino group transfer reaction is based on previously reported reaction conditions such as (N-tosylimino)-phenyl-λ 3 -iodane in the presence of I 2 as a catalyst [34,36]. In the initial experiment, we investigated the reaction of thioanisole 1a (1 equiv.) with (N-tosylimino)-phenyl-λ 3 -iodane 2a (1.2 equiv.) in the presence of a catalytic amount of both I 2 and tetrabutylammonium iodide (TBAI) as an additive under various solvents at room temperature (Table 1, entries 1-9). We have found that dichloromethane is an efficient solvent for the metal-free imination reaction of thioanisole 1a using (N-tosylimino)-phenyl-λ 3 -iodane 2a. The presence of TBAI as an additive did not affect this reaction (entry 10). However, in the absence of I 2 as a catalyst, the reaction dramatically changed, resulting in a low yield of the formation of the desired N-tosyl sulfilimine 3a (entries 11 and 12). Extension of the reaction time was effective for the desired product 3a yield (entry 14). Decreasing the amount of I 2 catalyst from 10 mol% to 2 mol% increased the yield of N-tosyl sulfilimine 3a (entries [14][15][16]. These results implied that the slow generation of the activated species was very important for this reaction because the species generated from (N-tosylimino)-phenyl-λ 3 -iodane 2a and I 2 were probably unstable in the reaction mixtures. Meanwhile, further reduction of the amount of I 2 catalyst and a longer reaction time led to a decreased amount of the desired product 3a (entries 17 and 18). Finally, performing the reaction under the dark conditions slightly suppressed the product yield, which supports a radical pathway in the reaction mixtures (entry 19) [36]. Table 1. Optimization of imination reaction of thioanisole 1a using (N-tosylimino)-phenyl-λ 3 -iodane 2a 1 .
Moreover, the reaction of triphenylphosphine 4 with (N-tosylimino)-phenyl- 3 -iodane 2a under optimized conditions also allowed the transfer reaction of N-tosyl sulfonylimino group to give the (N-tosylimino)-triphenylphosphorane 5 in excellent yield (Scheme 2). The structure of 5 was confirmed by a single crystal X-ray crystallography (see Supplementary Materials) [37]. Compared to the previously reported preparation of 5 using imino- 3 -iodanes, our reaction proceeds under very mild conditions and affords the product in higher yields [38,39].

Scheme 2.
Transfer reaction of N-tosyl sulfonylimino groups to triphenylphosphine 4. Moreover, the reaction of triphenylphosphine 4 with (N-tosylimino)-phenyl-λ 3 -iodane 2a under optimized conditions also allowed the transfer reaction of N-tosyl sulfonylimino group to give the (N-tosylimino)-triphenylphosphorane 5 in excellent yield (Scheme 2). The structure of 5 was confirmed by a single crystal X-ray crystallography (see Supplementary Materials) [37]. Compared to the previously reported preparation of 5 using imino-λ 3 -iodanes, our reaction proceeds under very mild conditions and affords the product in higher yields [38,39].
Moreover, the reaction of triphenylphosphine 4 with (N-tosylimino)-phenyl- 3 -iodane 2a under optimized conditions also allowed the transfer reaction of N-tosyl sulfonylimino group to give the (N-tosylimino)-triphenylphosphorane 5 in excellent yield (Scheme 2). The structure of 5 was confirmed by a single crystal X-ray crystallography (see Supplementary Materials) [37]. Compared to the previously reported preparation of 5 using imino- 3 -iodanes, our reaction proceeds under very mild conditions and affords the product in higher yields [38,39].

Mechanistic Study
To clarify the mechanism of metal-free sulfonylimino group transfer reaction, we have performed several blank experiments (Scheme 3). Based on the previously reported experiment, a amidyl radical precursor like N,N-diiodotosylamide or a related species might be generated from (N-tosylimino)-phenyl-λ 3 -iodane 2a with I 2 [34][35][36]40]. A radical mechanism is plausible because performing the reaction under dark conditions results in relatively low yields of product 3a (Table 1,  entry 20). Therefore, the presence of a radical scavenger such as TEMPO or BHT in the reaction would be effective for identification of the reaction mechanism. In the case of both reactions, the desired sulfilimine 3a was detected in the reaction mixtures in low yields around 11% as compared to 88% without the radical scavenger, which implies that the amidyl radical species were involved under the reaction mixture. When benzene was added to the reaction instead of thioanisole 1a, azepine or N-phenyl-p-toluenesulfonamide was not detected and only p-toluenesulonamide was recovered from the reaction mixtures. This result suggested that highly active nitrene species were not present under the reaction conditions. To clarify the mechanism of metal-free sulfonylimino group transfer reaction, we have performed several blank experiments (Scheme 3). Based on the previously reported experiment, a amidyl radical precursor like N,N-diiodotosylamide or a related species might be generated from (Ntosylimino)-phenyl- 3 -iodane 2a with I2 [34][35][36]40]. A radical mechanism is plausible because performing the reaction under dark conditions results in relatively low yields of product 3a (Table 1,  entry 20). Therefore, the presence of a radical scavenger such as TEMPO or BHT in the reaction would be effective for identification of the reaction mechanism. In the case of both reactions, the desired sulfilimine 3a was detected in the reaction mixtures in low yields around 11% as compared to 88% without the radical scavenger, which implies that the amidyl radical species were involved under the reaction mixture. When benzene was added to the reaction instead of thioanisole 1a, azepine or Nphenyl-p-toluenesulfonamide was not detected and only p-toluenesulonamide was recovered from the reaction mixtures. This result suggested that highly active nitrene species were not present under the reaction conditions.

Proposed Reaction Mechanism
From blank experiments and previously related results involving the amidyl radical species from imino- 3 -iodane 2a with I2 [34][35][36]40], we proposed the reaction mechanism of imination (Scheme 4). Initially, (N-tosylimino)-phenyl- 3 -iodane 2a reacted with I2 to produce N,Ndiiodotosylamide 6 (or related species) followed by generation of the amidyl radical 7 and iodine radical under the reaction conditions. The generated amidyl radical 7 was trapped by thioanisole 1a to afford the intermediate compound 8, followed by loss of iodine radical to give the desired sulfilimine product 3a and reproduced I2. The regenerated I2 would continue the next catalytic cycle.

Proposed Reaction Mechanism
From blank experiments and previously related results involving the amidyl radical species from imino-λ 3 -iodane 2a with I 2 [34][35][36]40], we proposed the reaction mechanism of imination (Scheme 4). Initially, (N-tosylimino)-phenyl-λ 3 -iodane 2a reacted with I 2 to produce N,N-diiodotosylamide 6 (or related species) followed by generation of the amidyl radical 7 and iodine radical under the reaction conditions. The generated amidyl radical 7 was trapped by thioanisole 1a to afford the intermediate compound 8, followed by loss of iodine radical to give the desired sulfilimine product 3a and reproduced I 2 . The regenerated I 2 would continue the next catalytic cycle.

General Experimental Remarks
All reactions were performed under dry argon atmosphere with flame-dried glassware. All

General Experimental Remarks
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 was distilled from CaH 2 immediately prior to use. Melting points were determined in an open capillary tube with a Mel-temp II melting point apparatus. Infrared spectra were recorded on a Perkin-Elmer 1600 series FT-IR spectrophotometer, and peaks were reported in reciprocal centimeters (cm -1 ). 1 H NMR spectra were recorded on a Varian Inova 500 and 300 MHz NMR spectrometer; 13 C NMR spectra were recorded on Varian Inova 500 and Varian 300 MHz NMR spectrometers at 125 and 75 MHz, respectively. Chemical shifts are reported in parts per million (ppm). 1 H and 13 C chemical shifts are referenced relative to tetramethylsilane. X-ray crystal analysis was performed by Rigaku RAPID II XRD Image Plate using graphite-monochromated MoKα radiation (λ = 0.71073 Å) at 173 K. (N-p-Tosylimino)phenyl-λ 3 -iodane 2a [41], (N-p-nosylimino)phenyl-λ 3 -iodane 2b [42], (N-o-nosylimino)phenyl-λ 3 -iodane 2c [43], and N-(phenylsulfonylimino)-phenyl-λ 3 -iodane 2d [44] were prepared according to the reported procedures.

4.2.
General Procedure for Imination of Sulfides 1 with Imino-phenyl-λ 3 -iodane 2 in the Presence of I 2 Imino-λ 3 -iodane 2 (0.12-0.24 mmol) was added at room temperature to a stirred mixture of sulfide 1 (0.10-0.20 mmol) and I 2 (0.002-0.004 mmol) in dichloromethane (1.0-2.0 mL). The reaction was stirred at room temperature for 24 h. After the reaction, 5% aqueous Na 2 S 2 O 3 (2.5-5.0 mL) was added to the mixture and the solution was extracted with ethyl acetate. The organic layer was dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was separated by column chromatography using the Hexane-EtOAc (1:1 to 0:100) to afford the pure product 3.