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. 2020 Apr 22;5(17):10191–10199. doi: 10.1021/acsomega.0c01086

Selective Synthesis of N-Cyano Sulfilimines by Dearomatizing Stable Thionium Ions

Sang Mee Kim †,‡, On-Yu Kang †,§, Hwan Jung Lim †,∥,*, Seong Jun Park †,*
PMCID: PMC7203956  PMID: 32391507

Abstract

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For the selective synthesis of N-cyano sulfilimines, we have developed a new method based on the soft–soft interaction between thionium ion electrophiles and cyanonitrene nucleophiles. The stable thionium ion was successfully obtained by oxidative dearomatization using phenyliodine (III) diacetate (PIDA) in N,N-dimethylformamide (DMF). The sulfur imination reactions were tolerant to a wide range of functional groups and exhibited high selectivities and excellent yields. The existence of thionium ion intermediates was confirmed by ultraviolet/visible (UV/vis) spectroscopy and 1H NMR experiments.

Introduction

Sulfilimines―mono-aza analogues of sulfoxides―were first reported in 1921.1 The S–N bond in sulfilimines is more reactive and polarized than the S–O bond in sulfoxides (Figure 1a).2 Due to the interesting features of this moiety, sulfilimines have played important roles in a broad range of fields, including synthetic chemistry,3 catalysis,4 crop protection,5 and medicinal chemistry.6 For example, in sulfilimine-applied organic reactions, there are aza-Mislow–Evans reactions,3a Diels–Alder reactions with furan and acyclic dienes,3b dichloroketene-induced cyclization reactions,3c the syntheses of γ-butyrolactams3d and α-hydroxy-β-amino acid derivatives,3e oxidative Mannich reactions,3f the direct thioamination of arynes,3g and the synthesis of new palladacycles.4 In crop protection, the discovery of sulfoxaflor by Dow AgroSciences (Figure 1b) stimulated a large number of subsequent investigations.7 With regards to drug discovery, AstraZeneca and Bayer employed sulfoximine-containing substances in selective kinase inhibitors, which are clinical candidates AZD67388a and BAY1000394.8b Researchers at AstraZeneca and Bayer demonstrated that one-atom replacement at the sulfur core—from oxygen to nitrogen—led to a compound with highly enhanced absorption, distribution, metabolism, and excretion (ADME) properties.8 For recent applications of these moieties inside living systems, the sulfilimine bond—a bond between methionine sulfur and hydroxylysine nitrogen—was first identified in native biomolecules.9 In addition, new bioorthogonal reactions using the sulfilimine chemistry have been reported for the development of an alternative approach to well-known click chemistry.10 In short, there has been an increasing awareness of the versatility of sulfilimine-based compounds as important reagents in organic synthesis and as highly potent molecules in drug development and agrochemical research (Figure 1b).

Figure 1.

Figure 1

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(a) Selected sulfur(IV) functional groups. (b) Biologically active N-cyano sulfilimines and sulfoximines.12

In general, the nitrogen end of the sulfilimine linkage is stabilized by strong electron-withdrawing groups (Figure 1a).2 Among the possible diversity of the imine nitrogen, we are particularly interested in the cyano substituent, which exhibits high metabolic stability, a powerful electron-withdrawing nature, and improved ADME-toxicology profiles.11

Few studies have demonstrated the formation of N-cyano sulfilimines from sulfides.13,14 As shown in Figure 2a, strategies include using sulfonium salt intermediates, adding halogenating reagents (e.g., N-halosuccinimides and t-BuOCl) to sulfides, and undergoing nucleophilic sulfur imination.13 Swern reported that cyanonitrene is formed by the reaction of t-butyl hypochlorite and sodium cyanamide.13a,13b However, N-sodio-N-chlorocyanamide was generated at a very low temperature using flammable t-butyl hypochlorite, which did not seem to be attractive from a practical synthesis perspective. For other oxidative imination approaches, Bolm reported that the combination of sulfides with N–bromosuccinimide (NBS), cyanamide, and sodium t-butoxide produces the desired cyano sulfilimines (Figure 2a).13c Although a well-behaved procedure, this procedure was limited using a strong base and the production of the undesirable sulfoxide. Consequently, practical procedures of synthesizing biologically active N-cyano sulfilimine (Figure 1b) are strongly required.

Figure 2.

Figure 2

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(a) Previously reported oxidative imination approach.13 (b) Our thionium ion approach.13b,14a,15,16

For the selective synthesis of the desired N-cyano sulfilimine, the in situ formation of the thionium ion and subsequent nucleophilic substitution with a cyanogen amine was envisaged. In the reported approaches (Figure 2a), a sulfonium salt was generally used as an unstable electrophile, which produced a significant amount of undesirable sulfoxide. To achieve the proper electrophile–nucleophile interaction, we designed a new reaction that proceeded via the intramolecular formation of thionium ions, which may act as stable softer electrophiles (Figure 2b). In principle, ortho- and para-substituted aromatic thionium ions could be formed by the oxidative dearomatization of anilides.17 Among the possible oxidants, hypervalent iodine (III) reagents have been widely used because of their moderate reactivity and broad applicability.18 For the softer nucleophile, a cyanamide/phenyliodine (III) diacetate (PIDA) system, which generated a nitrene or nitrene-like intermediate,13b,14a,16 was applied in this study.

Results and Discussion

Initially, the reaction of the iodine (III) reagents with anilide 1 and H2NCN was investigated in various solvents, such as CH2Cl2,14a CH3CN,14d and N,N-dimethylformamide (DMF).14e The combination of sulfide 1 with PIDA (1 equiv) and H2NCN (1 equiv) in CH2Cl2 and CH3CN for 5.5 h at room temperature produced a low yield of the desired sulfilimine 2a (each 27%, Table 1, entries 1 and 2). In the case of using DMF as a solvent, however, N-cyano sulfilimine 2a was obtained with a 57% yield (entry 3). Thus, this reaction was substantially influenced by the choice of the solvent. These preliminary results support the hypothesis that DMF would promote the formation of thionium ions.19 Changing the amount of PIDA (from 0.1 to 1.0 equiv) helped to increase the yield (Table 1, entries 3 to 6), whereas excess PIDA led to negative effects (entry 7).20 Then, we screened the amount of cyanamide (entries 3, 8, and 9), and the best result was obtained when 3 equiv of cyanamide were added. For the 1H NMR study of the mixture of PIDA and H2NCN in deuterated DMF, we found that the proton peak corresponding to cyanamide rapidly disappeared. Thus, a sufficient amount of cyanamide is required to produce the desired N-cyano sulfilimine 2a. A combination of 1 equiv of sulfide 1, 1 equiv of PIDA, and 3 equiv of H2NCN in DMF prove to be the most effective (entry 9). As shown in Table 1 (entry 10), the attempt to use phenyliodine (III) bis(trifluoroacetate) (PIFA)18f,21 was unsuccessful.22

Table 1. Imination Reaction of Sulfide 1 Using Iodine (III) Reagents and Cyanamide.

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  reaction conditionsb
  
entry iodine (III) (equiv)a H2NCN (equiv) solvent yield (%)c
1 PIDA (1.0) 1.0 CH3CN 27
2 PIDA (1.0) 1.0 CH2Cl2 27
3 PIDA (1.0) 1.0 DMF 57
4 PIDA (0.1) 1.0 DMF 8
5 PIDA (0.5) 1.0 DMF 24
6 PIDA (2.0) 1.0 DMF 53
7 PIDA (3.0) 1.0 DMF d
8 PIDA (1.0) 2.0 DMF 74
9 PIDA (1.0) 3.0 DMF 80
10 PIFA (1.0) 1.0 DMF d
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a

PIDA: phenyliodine(III) diacetate, PIFA: phenyliodine(III) bis(trifluoroacetate).

b

For highlighting the addition order of reagents, to a solution of sulfide 1 and iodine (III) reagent in DMF was added H2NCN in DMF at room temperature (RT).

c

After column chromatography.

d

No desired reaction.

Next, the scope of the reaction was examined using the optimized reaction conditions (Scheme 1). 2- or 4-Thiomethyl phenyl compounds proved to be generally excellent substrates for this transformation. Excellent yields of anilides, acetate, and benzoyl, for example, were all obtained (2–9, 11–14). The X-ray crystal structures of N-cyano sulfilimine 2a are illustrated.23 For sulfilimine 10, a moderate yield was observed when using N-(2-(methylthio)phenyl)pyridin-2-amine as a substrate. Interestingly, the yields of the 4-substituted sulfides (3, 5, 7, 9) were better than those of the 2-substituted ones (2a, 4, 6, 8). In the case of compounds 11–14, high yields were also obtained.

Scheme 1. Reaction Scope with Various Sulfides.

Scheme 1

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To seek insight into the mechanism and find evidence of the thionium ion species, we performed control experiments (Table 2). For the previously reported sulfonium salt-mediated approach (entry 1, method i),13c the unwanted sulfur oxidation reaction predominated over sulfilimine formation. Interestingly, in the absence of cyanonitrene, the Pummerer rearrangement products 2d, 2e,24 and sulfoxide 2c were obtained in low yields (entry 2, method ii). In contrast to the sulfonium salt electrophile, the thionium ion only generated a small quantity of sulfoxide 2c after the H2O workup (entry 1 vs 2). These results clearly demonstrated the existence of a stable thionium ion. When trifluoroacetamide was applied in this transformation as an imination source, the desired sulfilimine 2f was observed in only trace amounts (entry 3, method iii) We assume that the nitrene or nitrene-like intermediate could not be generated in the PIDA/H2NCOCF3 system.25 For 3-(S-methylsulfilimidoyl)phenyl compound 2g, no desired reaction occurred (entry 4). Importantly, this result indirectly demonstrates the formation of thionium ions, because 2- and 4-substituted compounds, which have conjugation systems, exhibited an excellent transformation.

Table 2. Control Experiments.

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a

R’ = C(O)Ph.

b

Method i: NBS (1.5 equiv), t-BuOK (1.2 equiv), H2NCN (1.3 equiv), MeOH, RT, 4 h; method ii: PIDA (1 equiv), DMF, RT, 5.5 h; method iii: PIDA (1 equiv), H2NC(O)CF3 (1 equiv), DMF, RT, 5.5 h; method iv: PIDA (1 equiv), H2NCN (1 equiv), DMF, RT, 5.5 h.

c

After column chromatography.

To determine the mechanism of our thionium ion approach, we carried out an extensive UV and 1H NMR investigation to monitor the reaction of sulfide 1 with PIDA.

The ultraviolet/visible (UV/vis) spectrum of 1 with combined PIDA was illustrated in Figure 3a. A solution of N-phenylbenzamide (without sulfide) and PIDA in DMF was also measured and used as a control experiment. The spectrum of each solvent showed different spectroscopic characteristics at 346 nm (acetonitrile, ACN), 350 nm (dichloromethane, DCM), and 358 nm (N,N-dimethylformamide, DMF). In the case of the mixture of N-phenylbenzamide in DMF, the characteristic band at 343 nm was observed. If larger conjugation systems are present, the absorption peak wavelengths tend to appear in regions where the wavelength is large, and the absorption peaks tend to be larger.26 Consequently, the UV/vis study suggested that DMF is the best solvent for this transformation.

Figure 3.

Figure 3

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(a) UV absorption spectra of a solution of sulfide 1 with PIDA in various solvents. (b) 1H NMR studies of a solution of sulfide 1 with PIDA in deuterated DMF.

Figure 3b shows the 1H NMR study results, which demonstrate the formation of the thionium ion. 1H NMR spectra of the reaction mixture of sulfide 1 and PIDA in deuterated DMF was obtained with respect to the reaction time. The remaining percent of each peak was calculated (Figure 3B, equation). Interestingly, Ha (NH of 1, black color) and He (protons of PIDA, green color) displayed a similar decreased pattern until 2 h, while the peak corresponding to PIDA rapidly disappeared after that time. In the case of Hb (S-methyl of 1, red color) and Hc (aromatic proton of 1, blue color), the same trend was observed. Note that the 4-position proton (Hd, pink color) was almost unchanged for 6 h.27

Hence, the UV/vis spectroscopy and 1H NMR studies lead us to conclude that the thionium ion is formed by oxidative dearomatization.

Conclusions

In summary, we have developed a thionium ion-mediated reaction and demonstrated that the soft–soft interaction between thionium ions and cyanonitrene would be a better method to access the N-cyano sulfilimine functionality. The mechanism involving the formation of stable softer thionium ion electrophiles was undoubtedly proven by (i) the sulfur imidation of the reactive functional group-substituted thioanisoles at the 2- and 4-position and (ii) UV/vis spectroscopy and 1H NMR studies of the solution of sulfide 1 and PIDA. Further investigations that aim to expand the scope of this transformation using harder nucleophiles are in progress in our laboratory.

Experimental Section

General Information

Analytical thin-layer chromatography (TLC) was performed on Kieselgel 60 F254 glass plates precoated with a 0.2 mm thickness of silica gel. The TLC plates were visualized by UV (254 nm), potassium permanganate, or ceric ammonium molybdate stain. Flash chromatography was carried out with Kieselgel 60 (230–400 mesh) silica gel. Melting points: Barnstead/Electrothermal 9300, measurements were performed in open glass capillaries. IR spectra: Bruker α-P. NMR spectra: Bruker AV 300 MHz (1H NMR: 300 MHz, 13C NMR: 75 MHz), AV 400 MHz (1H NMR: 400 MHz, 13C NMR: 100 MHz), AV 500 MHz (1H NMR: 500 MHz, 13C NMR: 125 MHz), and AV2 500 MHz (19F NMR: 470 MHz), the spectra were recorded in CDCl3, MeOD, and DMSO-d6 using tetramethylsilane (TMS) as the internal standard and are reported in ppm. 1H NMR data are reported as follows: (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublet, m = multiplet; coupling constant(s) J are given in Hz; integration, proton assignment). High-resolution mass spectra (HRMS): JEOL JMS-700. X-ray crystallography: Bruker SMART APEX II X-ray diffractometer. UV–VIS spectra: SCINCO S-4100 diffuse reflectance-ultraviolet/visible (DR-UV/VIS) spectrophotometer. All solvents were purified using a column filter solvent purification system before use unless otherwise indicated. Reagents were purchased and used without further purification.

General Imination Method

To a solution of sulfide 1 (0.2 mmol) and PhI(OAc)2 (0.2 mmol) in DMF (1 mL) was added H2NCN (0.6 mmol) in DMF (1 mL) at RT. The reaction mixture was stirred at RT for 5.5 h and quenched with water. The reaction mixture was extracted with CH2Cl2 (30 mL). The organic layer was dried over MgSO4, filtered, and evaporated. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired product.

(E)-N-(2-(N-Cyano-S-methylsulfinimidoyl)phenyl)benzamide (2a)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 2a as a white solid (44 mg, 79% yield). mp 173–174 °C; IR (KBr): ν 2135 (CN), 1314, 1254, 1165, 960, 760 cm–1; 1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 7.9 Hz, 2H), 7.74 (t, J = 7.7 Hz, 1H), 7.62–7.69 (m, 2H), 7.58 (t, J = 7.5 Hz, 2H), 7.48 (d, J = 7.6 Hz, 1H), 3.19 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 160.1 (CO), 135.9, 134.1, 133.6, 132.8, 132.6, 128.7, 128.2, 128.0, 126.5, 126.3, 120.8 (CN), 35.5 (CH3); HRMS (EI) calcd for C15H13N3OS 283.0779, found 283.0763.

(E)-N-(2-(N-Cyano-S-methylsulfinimidoyl)–5-(trifluoromethyl)phenyl)benzamide (2b)

To a solution of sulfide 1 (155 mg, 0.5 mmol) and PhI(OAc)2 (161 mg, 0.5 mmol) in DMF (1 mL) was added H2NCN (63 mg, 1.5 mmol) in DMF (1 mL) at RT. The reaction mixture was stirred at RT for 5.5 h and quenched with water. The reaction mixture was extracted with CH2Cl2 (30 mL). The organic layer was dried over MgSO4, filtered, and evaporated. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 2b as a white solid (104 mg, 59% yield). mp 146–147 °C; IR (KBr): ν 2154 (CN), 1662, 1534, 1475, 1338, 1283, 980, 704 cm–1; 1H NMR (500 MHz, CDCl3) δ 10.63 (s, 1H), 8.26 (d, J = 7.6 Hz, 2H), 7.96 (dd, J = 4.7 Hz, J = 8.7 Hz, 2H), 7.60 (dd, J = 7.3 Hz, J = 7.6 Hz, 1H), 7.49–7.62 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 167.1 (CO), 137.8, 135.5 (q, J = 33.4 Hz, CF3), 133.6, 133.0, 131.8, 128.9, 128.0, 127.6, 124.1, 123.5, 122.7, 121.4(CN), 37.1(CH3) 19F NMR (471 MHz, CDCl3) δ −63.2 (s, CF3); HRMS (EI) calcd for C16H12F3N3OS 351.0653, found 351.0656.

N-(2-(Methylsulfinyl)phenyl)benzamide (2c)

To a solution of sulfide 1 (97 mg, 0.4 mmol) and NBS (110 mg, 0.6 mmol) in MeOH (1 mL) were added t-BuOK (54 mg, 0.48 mmol) and H2NCN (21 mg, 0.52 mmol) in MeOH (1.5 mL) at RT. The reaction mixture was stirred at 0 °C for 4 h and quenched with water. The reaction mixture was extracted with CH2Cl2 (30 mL). The organic layer was dried over MgSO4, filtered, and evaporated. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the sulfoxide 2c as a white solid (81 mg, 78% yield). 1H NMR (300 MHz, CDCl3) δ 11.48 (s, 1H), 8.67 (d, J = 9.0 Hz, 1H), 8.03 (d, J = 7.5 Hz, 2H), 7.64 (dd, J = 2.3 Hz, J = 8.9 Hz, 1H), 7.46–7.60 (m, 3H), 7.42 (d, J = 2.3 Hz, 1H), 2.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.3 (CO), 140.8, 133.8, 132.7, 132.1, 128.9, 127.5, 127.3, 125.8, 123.5, 123.0, 40.8 (CH3).

((2-Benzamidophenyl)thio)methyl Acetate (2d) and N-(2-((Hydroxymethyl)thio)phenyl)benzamide (2e)

Sulfide 1 (121 mg, 0.5 mmol) and PhI(OAc)2 (161 mg, 0.5 mmol) were dissolved in DMF (1 mL), and the reaction mixture was stirred at RT for 5.5 h and quenched with water. The reaction mixture was extracted with CH2Cl2 (30 mL). The organic layer was dried over MgSO4, filtered, and evaporated. The residue was purified by column chromatography on silica gel (n-Hex/ EtOAc = 10:1) to give the sulfoxide 2c (27 mg, 26% yield), the compound 2d as a colorless liquid (8 mg, 5% yield), and the compound 2e as a white solid (5.1 mg, 4% yield). 2d: IR (neat): ν 3253, 1739, 1648, 1519, 1471, 1306, 1226, 1072, 1025, 757, 710 cm–1; 1H NMR (500 MHz, CDCl3) δ 9.34 (s, 1H), 8.64 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 7.5 Hz, 2H), 7.64 (d, J = 7.7 Hz, 1H), 7.59 (dd, J = 7.2 Hz, J = 7.4 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H), 7.47 (dd, J = 7.8 Hz, J = 7.9 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 5.24 (s, 2H), 1.81 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 170.0 (CO), 165.0 (CO), 140.3, 136.1, 134.7, 132.1, 131.2, 128.9, 127.1, 124.5, 121.4 (CN), 120.4, 69.9 (CH2), 20.5 (CH3); HRMS (EI) calcd for C16H15NO3S 301.0773, found 301.0773. 2e: mp 97-98 °C; IR (KBr): ν 1986, 1645, 1509, 1465, 1068, 1024, 911, 742 cm–1; 1H NMR (500 MHz, CDCl3) δ 9.30 (s, 1H), 8.64 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 7.6 Hz, 2H), 7.67 (d, J = 7.7 Hz, 1H), 7.48–7.60 (m, 5H), 7.17 (t, J = 7.6 Hz, 1H), 4.82 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 165.2 (CO), 140.6, 136.4, 134.7, 132.1, 128.9, 127.2, 124.6, 120.8, 120.4, 52.5 (CH2).

(E)-N-(4-(N-Cyano-S-methylsulfinimidoyl)phenyl)benzamide (3)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 3 as a white solid (48 mg, 85% yield). mp 173–174 °C; IR (KBr): ν 2141 (CN), 1322, 1250, 1143, 959, 841, 768 cm–1; 1H NMR (500 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.07 (d, J = 8.7 Hz, 2H), 7.97 (d, J = 7.7 Hz, 2H), 7.90 (d, J = 8.3 Hz, 2H), 7.63 (dd, J = 7.3 Hz, J = 7.5 Hz, 1H), 7.56 (t, J = 7.5 Hz, 2H), 3.15 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 166.2 (CO), 143.3, 134.4, 132.1, 130.0, 128.6, 127.9, 127.8, 120.9, 120.5 (CN), 34.7 (CH3); HRMS (FAB) calcd for C15H14N3OS 284.0858, found 284.0860.

tert-Butyl (E)-(2-(N-cyano-S-methylsulfinimidoyl)phenyl)carbamate (4)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 4 as a white solid (31 mg, 55% yield). mp 132–133 °C; IR (KBr): ν 2141 (CN), 1286, 1235, 1156, 990, 762 cm–1; 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.71–7.80 (m, 2H), 7.55 (dd, J = 7.3, J = 8.5, 1H) 7.29 (t, J =7.7, 1H), 3.10 (s, 3H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 153.5 (CO), 138.2, 134.2, 127.7, 125.5, 123.9, 120.8 (CN), 82.0, 35.7 (CH3), 29.7 (C), 28.2 (3 x C, CH3); HRMS (EI) calcd for C13H17N3O2S 279.1041, found 279.1057.

tert-Butyl (E)-(4-(N-cyano-S-methylsulfinimidoyl)phenyl)carbamate (5)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 5 as a white solid (60 mg, quantitative yield). mp. 123–124 °C; IR (KBr): ν 2141(CN), 1314, 1229, 1147, 961, 830, 762 cm–1; 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.6 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.22 (s, 1H), 2.99 (s, 3H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 152.2 (CO), 143.6, 128.2, 127.5, 120.6 (CN), 119.2, 81.6, 36.1 (CH3), 29.7 (C), 28.2 (3 × C, CH3); HRMS (FAB) calcd for C13H18N3O2S 280.1120, found 280.1118.

(E)-N-(2-(N-Cyano-S-methylsulfinimidoyl)phenyl)acetamide (6)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 6 as a colorless liquid (28 mg, 63% yield). IR (neat): ν 2138 (CN), 1684, 1476, 1253, 1187, 983, 767 cm–1; 1H NMR (400 MHz, MeOD) δ 8.13 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 7.7 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 7.9 Hz, 1H), 3.17 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, MeOD) δ 173.2 (CO), 137.1, 135.1, 134.4, 129.5, 127.6, 126.4, 123.1 (CN), 36.8 (CH3), 22.7 (CH3); HRMS (EI) calcd for C10H11N3OS 221.0623, found 221.0610.

(E)-N-(4-(N-Cyano-S-methylsulfinimidoyl)phenyl)acetamide (7)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 7 as a white solid (29 mg, 66% yield). mp 175–176 °C; IR (KBr): ν 2145 (CN), 1685, 1444, 1380, 1161, 973, 838, 758 cm–1; 1H NMR (500 MHz, MeOD) δ 7.88 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 8.6 Hz, 2H), 3.10 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, MeOD) δ 172.2 (CO), 145.0, 130.9, 128.9, 122.7 (CN), 121.7, 36.4 (CH3), 24.2 (CH3); HRMS (FAB) calcd for C10H12N3OS 222.0701, found 222.0711.

(E)–2-(N-Cyano-S-methylsulfinimidoyl)phenyl Acetate (8)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 8 as a colorless liquid (25 mg, 60% yield). IR (neat): ν 2151 (CN), 1725, 1456, 1371, 1182, 963, 865, 755 cm–1; 1H NMR (300 MHz, CDCl3) δ 8.11 (d, J = 7.9 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.53 (dd, J = 7.6 Hz, J = 7.8 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 3.01 (s, 3H), 2.39 (s, 3H); 13C NMR; 168.4 (CO), 147.2, 134.2, 129.2, 128.0, 126.4, 123.4, 120.2 (CN), 36.2 (CH3), 20.7 (CH3).

(E)-4-(N-Cyano-S-methylsulfinimidoyl)phenyl Acetate (9)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 9 as a white solid (32 mg, 74% yield). mp 99–100 °C; IR (KBr): ν 2137 (CN), 1747, 1496, 1356, 1190, 952, 844, 759 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 3.02 (s, 3H), 2.34 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 168.6 (CO), 154.3, 133.1, 127.6, 123.8, 120.1 (CN), 36.7 (CH3), 21.1 (CH3); HRMS (EI) calcd for C10H11N3OS 221.0463, found 222.0478.

(E)-N-(Methyl(2-(pyridin-2-ylamino)phenyl)-λ4-sulfanylidene)cyanamide (10)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 10 as an orange solid (18 mg, 35% yield). mp 153–154 °C; IR (KBr): ν 2135 (CN), 1467, 1186, 967, 765 cm–1; 1H NMR (500 MHz, CDCl3) δ 8.39 (s, 1H), 8.16 (d, J = 5.1 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.57 (dd, J = 7.9 Hz, J = 8.6 Hz, 1H), 7.53 (dd, J = 7.8 Hz, J = 7.9 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 6.85 (dd, J = 5.8 Hz, J = 6.7 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 3.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.6, 147.5, 141.3, 138.3, 134.3, 128.1, 123.9, 123.6, 123.0, 121.0 (CN), 116.9, 111.4, 35.0 (CH3); HRMS (EI) calcd for C13H12N4S 256.0783, found 256.0793.

(E)-N-(2-(N-Cyano-S-methylsulfinimidoyl)phenyl)furan-2-carboxamide (11)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 11 as a white solid (43 mg, 80% yield). mp 82–83 °C; IR (KBr): ν 2146 (CN), 1310, 1167, 973, 759 cm–1; 1H NMR (400 MHz, CDCl3) δ 9.99 (s, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 7.9 Hz, 1H), 7.58–7.65 (m, 2H), 7.38 (t, J = 7.7 Hz, 1H), 7.31 (d, J = 3.6 Hz, 1H), 6.57–6.61 (m, 1H), 3.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.2 (CO), 146.5, 145.7, 136.8, 134.3, 127.7, 127.2, 126.9, 125.1, 120.8 (CN), 116.6, 112.6, 36.2 (CH3); HRMS (EI) calcd for C13H11N3O2S 273.0572, found 273.0569.

(E)-N-(2-(N-Cyano-S-methylsulfinimidoyl)phenyl)quinoline-2-carboxamide (12)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 12 as a white solid (62 mg, 91% yield). mp 125–126 °C; IR (KBr): ν 2148 (CN), 1313, 1185, 1132, 982, 839, 764 cm–1; 1H NMR (500 MHz, CDCl3) δ 11.24 (s, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 8.5 Hz, 1H), 8.01 (dd, J = 8.8 Hz, J = 9 Hz, 2H), 7.93 (d, J = 8.2 Hz, 1H), 7.84 (dd, J = 7.5 Hz, J = 7.8 Hz, 1H), 7.68 (t, J = 7.9 Hz, 2H), 7.47 (t, J =7.7 Hz, 1H), 3.21 (s. 3H); 13C NMR (125 MHz, CDCl3) δ 163.9 (CO), 148.0, 146.4, 138.1, 136.5, 134.2, 130.7, 130.1, 129.6, 128.8, 127.7, 127.6, 127.0, 124.8, 120.9 (CN), 118.6, 36.2 (CH3); HRMS (EI) calcd for C18H14N4OS 334.0888, found 334.0899.

(E)-1-(2-(N-Cyano-S-methylsulfinimidoyl)phenyl)-3-phenylurea (13)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 13 as a white solid (43 mg, 72% yield). mp 184–185 °C; IR (KBr): ν 2149 (CN), 1312, 1230, 1165, 963, 762 cm–1; 1H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 9.03 (s, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.65 (dd, J = 7.5 Hz, J = 7.9 Hz, 1H), 7.42–7.53 (m, 4H), 7.30 (dd, J = 7.7 Hz, J = 7.8 Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 3.18 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 154.0 (CO), 139.1, 137.0, 133.4, 132.0, 128.8, 126.6, 126.3, 124.4, 122.5, 120.9 (CN), 118.8, 35.1 (CH3); HRMS (EI) calcd for C15H14N4OS 298.0904, found 298.0896.

(E)–2-(N-Cyano-S-methylsulfinimidoyl)phenylbenzoate (14)

This follows the general imination method. The residue was purified by column chromatography on a silica gel (EtOAc only) to give the desired sulfilimine 14 as a colorless liquid (68 mg, quantitative yield). IR (neat): ν 2151 (CN), 1252, 1202, 1052, 969, 761, 707 cm–1; 1H NMR (400 MHz, CDCl3) δ 8.16–8.22 (m, 3H), 7.72 (dd, J = 7.9 Hz, J = 8.4 Hz, 2H), 7.58 (dd, J = 7.7 Hz, J = 8.0 Hz, 3H), 7.41 (d, J = 8.2 Hz, 1H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4 (CO), 147.6, 134.8, 134.3, 130.4, 129.8, 129.1, 128.1, 127.5, 126.5, 123.5, 120.2 (CN), 36.4 (CH3); HRMS (EI) calcd for C15H12N2O2S 284.0619, found 284.0629.

For Figure 3a, Measurement Procedure of UV Absorption Spectra

To a solution of sulfide 1 (50 mg, 0.2 mmol) in the solvent (1 mL) was added PhI(OAc)2 (66 mg, 0.2 mmol) at RT. On shaking, a clear solution was obtained immediately. After maintaining the resulting solution at RT for 10 min, the measurement of UV absorption spectra was performed.

Acknowledgments

This work is supported by KRICT (KK1932-30, SKO1961-01, BSF20-320, and SI2031-40). The authors thank Dr. Chong-Hyeak Kim and Yoon Mi Choi for X-ray analyses. Also, the authors appreciate reviewer’s detailed comments and constructive suggestions.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c01086.

  • Copies of 1H and 13C spectra; UV/vis spectroscopy studies; 2D DEPT NMR of sulfide 1; 1H NMR studies of reaction mixture; X-ray data of 2a (PDF)

The authors declare no competing financial interest.

Supplementary Material

ao0c01086_si_001.pdf (3.4MB, pdf)

References

  1. Nicolet B. H.; Willard J. A new type of nitrogen-sulfur compounds: the action of chloramine-T on organic sulfides. Science 1921, 53, 217.17831200 [Google Scholar]
  2. a Gilchrist T. L.; Moody C. J. The Chemistry of sulfilimines. Chem. Rev. 1977, 77, 409–435. 10.1021/cr60307a005. [DOI] [Google Scholar]; b Oae S.Sulfoxides and Sulfilimines, Organic Chemistry of Sulfur; Plenum Press: New York, 1977; p 394. [Google Scholar]; c Furukawa N.; Oae S. Sulfilimines. Synthetic Applications and Potential Utilizations. Ind. Eng. Chem. Prod. Res. Dev. 1981, 20, 260–270. 10.1021/i300002a009. [DOI] [Google Scholar]; d Bizet V.; Hendriks C. M. M.; Bolm C. Sulfur imidations: access to sulfimides and sulfoximines. Chem. Soc. Rev. 2015, 44, 3378–3390. 10.1039/C5CS00208G. [DOI] [PubMed] [Google Scholar]
  3. a Dolle R. E.; Osifo K. I.; Li C.–S. Enantioselective synthesis of (+)-pinidine. Tetrahedron Lett. 1991, 32, 5029–5030. 10.1016/S0040-4039(00)93419-1. [DOI] [Google Scholar]; b Ruano J. L. G.; Alemparte C.; Clemente F. R.; Gutiérrez L. G.; Gordillo R.; Martin Castro A. M.; Rodriguez Ramos J. H. Cyclic Vinyl p-Tolyl Sulfilimines as Chiral Dienophiles: Diels–Alder Reactions with Furan and Acyclic Dienes. J. Org. Chem. 2002, 67, 2919–2925. 10.1021/jo016174w. [DOI] [PubMed] [Google Scholar]; c Padwa A.; Nara S.; Wang Q. Dichloroketene-induced cyclizations of vinyl sulfilimines: application of the method in the synthesis of (±)-desoxyeseroline. J. Org. Chem. 2005, 70, 8538–8549. 10.1021/jo051550o. [DOI] [PubMed] [Google Scholar]; d Marino J. P.; Zou N. Chemoselective syntheses of γ-butyrolactams using vinyl sulfilimines and dichloroketene. Org. Lett. 2005, 7, 1915–1917. 10.1021/ol050245m. [DOI] [PubMed] [Google Scholar]; e Raghavan S.; Mustafa S. Stereoselective synthesis of α-hydroxy-β-amino acid derivatives from β-hydroxy-γ, δ-unsaturated sulfilimine. Tetrahedron Lett. 2008, 49, 3216–3220. 10.1016/j.tetlet.2008.03.114. [DOI] [Google Scholar]; f Matsuo J.; Tanaki Y.; Ishibashi H. Oxidative Mannich Reaction of N-Carbobenzyloxy Amines with 1,3-Dicarbonyl Compounds. Org. Lett. 2006, 8, 4371–4374. 10.1021/ol0618095. [DOI] [PubMed] [Google Scholar]; g Yoshida S.; Yano T.; Misawa Y.; Sugimura Y.; Igawa K.; Shimizu S.; Tomooka K.; Hosoya T. Direct Thioamination of Arynes via Reaction with Sulfilimines and Migratory N-Arylation. J. Am. Chem. Soc. 2015, 137, 14071–14074. 10.1021/jacs.5b10557. [DOI] [PubMed] [Google Scholar]
  4. Thakur V. V.; Ramesh Kumar N. S. C.; Sudalai A. Sulfilimine palladacycles: stable and efficient catalysts for carbon–carbon coupling reactions. Tetrahedron Lett. 2004, 45, 2915–2918. 10.1016/j.tetlet.2004.02.069. [DOI] [Google Scholar]
  5. a Zhou S.; Jia Z.; Xiong L.; Yan T.; Yang N.; Wu G.; Song H.; Li Z. Chiral dicarboxamide scaffolds containing a sulfiliminyl moiety as potential ryanodine receptor activators. J. Agric. Food Chem. 2014, 62, 6269–6277. 10.1021/jf501727k. [DOI] [PubMed] [Google Scholar]; b Zhou S.; Gu Y.; Liu M.; Wu C.; Zhou S.; Zhao Y.; Jia Z.; Wang B.; Xiong L.; Yang N.; Li Z. Insecticidal Activities of Chiral N-Trifluoroacetyl Sulfilimines as Potential Ryanodine Receptor Modulators. J. Agric. Food Chem. 2014, 62, 11054–11061. 10.1021/jf503513n. [DOI] [PubMed] [Google Scholar]; c Zhou S.; Yan T.; Li Y.; Jia Z.; Wang B.; Zhao Y.; Qiao Y.; Xiong L.; Li Y.; Li Z. Novel phthalamides containing sulfiliminyl moieties and derivatives as potential ryanodine receptor modulators. Org. Biomol. Chem. 2014, 12, 6643–6652. 10.1039/C4OB00716F. [DOI] [PubMed] [Google Scholar]; d Hua X.; Mao W.; Fan Z.; Ji X.; Li F.; Zong G.; Song H.; Li J.; Zhou L.; Zhou L.; Liang X.; Wang G.; Chen X. Novel anthranilic diamide insecticides: design, synthesis, and insecticidal evaluation. Aust. J. Chem. 2014, 67, 1491–1503. 10.1071/ch13701. [DOI] [Google Scholar]; e Koerber K.; Wach J.; Kaiser F.; Pohlman M.; Deshmukh P.; Culbertson D. L.; Rogers W. D.; Gunjima K.; David M.; Braun F. J.; Thompson S.. Method of controlling ryanodine-modulator insecticide resistant insect, (BASF SE). WO Patent WO2014053406A1, 2014.; f Yu X.; Zhang Y.; Liu Y.; Li Y.; Wang Q. Synthesis and Acaricidal-and Insecticidal-Activity Evaluation of Novel Oxazolines Containing Sulfiliminyl Moieties and Their Derivatives. J. Agric. Food Chem. 2019, 67, 4224–4231. 10.1021/acs.jafc.9b00657. [DOI] [PubMed] [Google Scholar]
  6. a Andersen K. K.; Bhattacharyya J.; Mukhopadhyay S. K. Antimalarial sulfilimines and sulfoximines related to diaminodiphenyl sulfoxide and sulfone. J. Med. Chem. 1970, 13, 759–760. 10.1021/jm00298a049. [DOI] [PubMed] [Google Scholar]; b Strekowski L.; Henary M.; Kim N.; Michniak B. B. N-(4-bromobenzoyl)-S, S-dimethyliminosulfurane, a potent dermal penetration enhancer. Bioorg. Med. Chem. Lett. 1999, 9, 1033–1034. 10.1021/jm00298a049. [DOI] [PubMed] [Google Scholar]
  7. a Zhu Y.; Loso M. R.; Watson G. B.; Sparks T. C.; Rogers R. B.; Huang J. X.; Gerwick B. C.; Babcock J. M.; Kelley D.; Hegde V. B.; Nugent B. M.; Renga J. M.; Denholm I.; Gorman K.; DeBoer G. J.; Hasler J.; Meade T.; Thomas J. D. Discovery and characterization of sulfoxaflor, a novel insecticide targeting sap-feeding pests. J. Agric. Food Chem. 2011, 59, 2950–2957. 10.1021/jf102765x. [DOI] [PubMed] [Google Scholar]; b Babcock J. M.; Gerwick C. B.; Huang J. X.; Loso M. R.; Nakamura G.; Nolting S. P.; Rogers R. B.; Sparks T. C.; Thomas J.; Watson G. B.; Zhu Y. Biological characterization of sulfoxaflor, a novel insecticide. Pest Manage. Sci. 2011, 67, 328–334. 10.1002/ps.2069. [DOI] [PubMed] [Google Scholar]; c Watson G. B.; Loso M. R.; Babcock J. M.; Hasler J. M.; Letherer T. J.; Young C. D.; Zhu Y.; Casida J. E.; Sparks T. C. Novel nicotinic action of the sulfoximine insecticide sulfoxaflor. Insect Biochem. Mol. Biol. 2011, 41, 432–439. 10.1016/j.ibmb.2011.01.009. [DOI] [PubMed] [Google Scholar]
  8. a Foote K. M.; Nissink J. W. M.; McGuire T.; Turner P.; Guichard S.; Yates J. W. T.; Lau A.; Blades K.; Heathcote D.; Odedra R.; Wilkinson G.; Wilson Z.; Wood C. M.; Jewsbury P. J. Discovery and characterization of AZD6738, a potent inhibitor of ataxia telangiectasia mutated and Rad3 related (ATR) kinase with application as an anticancer agent. J. Med. Chem. 2018, 61, 9889–9907. 10.1021/acs.jmedchem.8b01187. [DOI] [PubMed] [Google Scholar]; b Siemeister G.; Luecking U.; Wengner A. M.; Lienau P.; Steinke W.; Schatz C.; Mumberg D.; Ziegelbauer K. BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono-and in combination treatment upon oral application. Mol. Cancer Ther. 2012, 11, 2265–2273. 10.1158/1535-7163.MCT-12-0286. [DOI] [PubMed] [Google Scholar]; c Lücking U. Sulfoximines: a neglected opportunity in medicinal chemistry. Angew. Chem., Int. Ed. 2013, 52, 9399–9408. 10.1002/anie.201302209. [DOI] [PubMed] [Google Scholar]
  9. a Vanacore R.; Ham A.–J. L.; Voehler M.; Sanders C. R.; Conrads T. P.; Veenstra T. D.; Sharpless K. B.; Dawson P. E.; Hudson B. G. A sulfilimine bond identified in collagen IV. Science 2009, 325, 1230–1234. 10.1126/science.1176811. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Bhave G.; Cummings C. F.; Vanacore R. M.; Kumagai-Cresse C.; Ero-Tolliver I. A.; Rafi M.; Kang J.-S.; Pedchenko V. P.; Fessler L. I.; Fessler J. H.; Hudson B. G. Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis. Nat. Chem. Biol. 2012, 8, 784–790. 10.1038/nchembio.1038. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Weiss S. J. Peroxidasin: tying the collagen-sulfilimine knot. Nat. Chem. Biol. 2012, 8, 740–741. 10.1038/nchembio.1050. [DOI] [PubMed] [Google Scholar]
  10. a Xiong F.; Lu L.; Sun T.–Y.; Wu Q.; Yan D.; Chen Y.; Zhang X.; Wei W.; Lu Y.; Sun W.–Y.; Li J. J.; Zhao J. A bioinspired and biocompatible ortho-sulfiliminyl phenol synthesis. Nat. Commun. 2017, 15912 10.1038/ncomms15912. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Lin S.; Yang X.; Jia S.; Weeks A. M.; Hornsby M.; S. Lee P. S.; Nichiporuk R. V.; Iavarone A. T.; Wells J. A.; Toste F. D.; Chang C. J. Redox-based reagents for chemoselective methionine bioconjugation. Science 2017, 355, 597–602. 10.1126/science.aal3316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fleming F. F.; Yao L.; Ravikumar P. C.; Funk L.; Shook B. C. Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore. J. Med. Chem. 2010, 53, 7902–7917. 10.1021/jm100762r. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. For patent application of bioactive N-cyano sulfilimine and sulfoximine, see; a Ahrens H.; Braun R.; Doerner-Rieping S.; Koehn A.; Lehr S.; Dietrich H.; Schmutzler D.; Gatzweiler E.; Rosinger C. H.. Herbicidal 3-(sulfin-/sulfonimidoyl)–benzamides, (Bayer). WO Patent WO2013124228A1, 2013.; b Gnamm C.; Oost T.. Substituted pyridones and pyrazinones and their use as inhibitors of neutrophil elastase activity, (Boehringer Ingelheim).WO Patent WO2015124563A1, 2015.; c Oost T.; Fiegen D.; Gnamm C.. Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity, (Boehringer Ingelheim). WO2014029830A1, 2014.
  13. a Swern D.; Ikeda I.; Whitfield G. F. Tetracovalent sulfur intermediates in iminosulfurane synthesis. Genesis of a potentially general ylid preparation. Tetrahedron Lett. 1972, 13, 2635–2638. 10.1016/S0040-4039(01)84894-2. [DOI] [Google Scholar]; b Hutchins M. G. K.; Swern D. A nonazide source of cyanonitrene and its interception by tertiary amines. Tetrahedron Lett. 1981, 22, 4599–4602. 10.1016/S0040-4039(01)82991-9. [DOI] [Google Scholar]; c Mancheño O. G.; Bistri O.; Bolm C. Iodinane- and Metal-Free Synthesis of N-Cyano Sulfilimines: Novel and Easy Access of NH-Sulfoximines. Org. Lett. 2007, 9, 3809–3811. 10.1021/ol7016577. [DOI] [PubMed] [Google Scholar]; d Arndt K. E.; Bland D. C.; Irvine N. M.; Powers S. L.; Martin T. P.; McConnell J. R.; Podhorez D. E.; Renga J. M.; Ross R.; Roth G. A.; Scherzer B. D.; Toyzan T. W. Development of a Scalable Process for the Crop Protection Agent Isoclast. Org. Process Res. Dev. 2015, 19, 454–462. 10.1021/acs.oprd.5b00007. [DOI] [Google Scholar]
  14. a Kemp J. E. G.; Ellis D.; Closier M. D. Penicillin N-cyanosulphilmines; cyanamide/iodobenzene diacetate, a convenient cyanonitrene reagent for N-cyano sulphilmines, sulphoximines, phosphinimines and aziridines. Tetrahedron Lett. 1979, 39, 3781–3784. 10.1016/S0040-4039(01)95523-6. [DOI] [Google Scholar]; b Ou W.; Chen Z.–C. Hypervalent iodine in synthesis XXXII: A novel way for the synthesis of N-sulfonylsulfilimines from sulfides and sulfonamides using iodosobenzene diacetate. Synth. Commun. 1999, 29, 4443–4449. 10.1080/00397919908086608. [DOI] [Google Scholar]; c Cho G. Y.; Bolm C. Metal-free imination of sulfoxides and sulfides. Tetrahedron Lett. 2005, 46, 8007–8008. 10.1016/j.tetlet.2005.09.070. [DOI] [Google Scholar]; d Mancheño O. G.; Bolm C. Synthesis of N-(1H)-Tetrazole Sulfoximines. Org. Lett. 2007, 9, 2951–2954. 10.1021/ol071302+. [DOI] [PubMed] [Google Scholar]; e Chen X. Y.; Buschmann H.; Bolm C. Sulfoximine-and sulfilimine-based dapson analogues; syntheses and bioactivities. Synlett 2012, 23, 2808–2810. 10.1055/s-0032-1317493. [DOI] [Google Scholar]; f Zenzola M.; Doran R.; Degennaro L.; Luisi R.; Bull J. A. Transfer of Electrophilic NH Using Convenient Sources of Ammonia: Direct Synthesis of NH Sulfoximines from Sulfoxides. Angew. Chem., Int. Ed. 2016, 55, 7203–7207. 10.1002/anie.201602320;. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Lohier J.–F.; Glachet T.; Marzag H.; Gaumont A.–C.; Reboul V. Mechanistic investigation of the NH-sulfoximination of sulfide. Evidence for λ6-sulfanenitrile intermediates. Chem. Commun. 2017, 53, 2064–2067. 10.1039/c6cc09940h. [DOI] [PubMed] [Google Scholar]
  15. a Padwa A.; Gunn Jr D. E.; Osterhout M. H. Application of the Pummerer reaction toward the synthesis of complex carbocycles and heterocycles. Synthesis 1997, 1997, 1353–1377. 10.1055/s-1997-1384. [DOI] [Google Scholar]; b Padwa A.; Waterson A. G. Synthesis of nitrogen heterocycles using the intramolecular pummerer reaction. Curr. Org. Chem. 2000, 4, 175–203. 10.2174/1385272003376300. [DOI] [Google Scholar]; c Padwa A.; Danca D. M.; Ginn J. D.; Lynch S. M. Application of the tandem thionium/N-acyliminium ion cascade toward heterocyclic synthesis. J. Braz. Chem. Soc. 2001, 12, 571–585. 10.1590/S0103-50532001000500002. [DOI] [Google Scholar]; d Feldman K. S. Modern Pummerer-type reactions. Tetrahedron 2006, 62, 5003–5034. 10.1016/j.tet.2006.03.004. [DOI] [Google Scholar]; e Akai S.; Kita Y. Recent advances in Pummerer reactions. Top. Curr. Chem. 2007, 274, 35–76. 10.1007/128_073. [DOI] [Google Scholar]; f Ovens C.; Martin N. G.; Proctoer D. J. A. Dearomatizing, Thionium Ion Cyclization for the Synthesis of Functionalized, Azaspirocyclic Cyclohexadienones. Org. Lett. 2008, 10, 1441–1444. 10.1021/ol8002095. [DOI] [PubMed] [Google Scholar]; g Smith L. H. S.; Coote S. C.; Sneddon H. F.; Procter D. J. Beyond the Pummerer reaction: recent developments in thionium ion chemistry. Angew. Chem., Int. Ed. 2010, 49, 5832–5844. 10.1002/anie.201000517. [DOI] [PubMed] [Google Scholar]
  16. a Borodkin G. I.; shubin V. G. Nitrenium ions: structure and reactivity. Russ. Chem. Rev. 2008, 77, 395–419. 10.1070/RC2008v077n05ABEH003760. [DOI] [Google Scholar]; b Mayr H.; Breugst M.; Ofial A. R. Farewell to the HSAB treatment of ambident reactivity. Angew. Chem., Int. Ed. 2011, 50, 6470–6505. 10.1002/anie.201007100. [DOI] [PubMed] [Google Scholar]
  17. a Adams R.; Way J. W. Quinone Imides. XXXV. o-Quinonedibenzimides. J. Am. Chem. Soc. 1954, 76, 2763–2769. 10.1021/ja01639a049. [DOI] [Google Scholar]; b Abraham C. J.; Paull D. H.; Scerba M. T.; Grebinski J. W.; Lectka T. Catalytic, Enantioselective Bifunctional Inverse Electron Demand Hetero-Diels–Alder Reactions of Ketene Enolates and o-Benzoquinone Diimides. J. Am. Chem. Soc. 2006, 128, 13370–13371. 10.1021/ja065754d. [DOI] [PubMed] [Google Scholar]; c Wolfer J.; Bekele T.; Abraham C. J.; Dogo-Isonagie C.; Lectka T. Catalytic, Asymmetric Synthesis of 1,4-Benzoxazinones: A Remarkably Enantioselective Route to α-Amino Acid Derivatives from o-Benzoquinone Imides. Angew. Chem., Int. Ed. 2006, 45, 7398–7400. 10.1002/anie.200602801. [DOI] [PubMed] [Google Scholar]; d Narayan R.; Manna S.; Antonchick A. P. Hypervalent iodine (III) in direct carbon–hydrogen bond functionalization. Synlett 2015, 26, 1785–1803. 10.1055/s-0034-1379912. [DOI] [Google Scholar]
  18. a Varvoglis A. Aryliodine (III) dicarboxylates,. Chem. Soc. Rev. 1981, 10, 377–407. 10.1039/cs9811000377. [DOI] [Google Scholar]; b Varvoglis A. Polyvalent Iodine Compounds in Organic Synthesis. Synthesis 1984, 1984, 709–726. 10.1055/s-1984-30945. [DOI] [Google Scholar]; c Moriarty R. M.; Vaid R. K. Carbon-carbon bond formation via hypervalent iodine oxidations. Synthesis 1990, 1990, 431–447. 10.1055/s-1990-26898. [DOI] [Google Scholar]; d Prakash O.; Saini N.; Sharma P. K. [Hydroxy(tosyloxy)iodo] benzene: a useful hypervalent iodine reagent for the synthesis of hetercocyclic compounds. Heterocycles 1994, 38, 409–431. 10.3987/REV-93-458. [DOI] [Google Scholar]; e Varvoglis A. Chemical transformations induced by hypervalent iodine reagents. Tetrahedron 1997, 53, 1179–1255. 10.1016/S0040-4020(96)00970-2. [DOI] [Google Scholar]; f Itoh N.; Sakamoto T.; Miyazawa E.; Kikugawa Y. Introduction of a Hydroxy Group at the Para Position and N-Iodophenylation of N-Arylamides Using Phenyliodine(III) Bis(Trifluoroacetate). J. Org. Chem. 2002, 67, 7424–7428. 10.1021/jo0260847. [DOI] [PubMed] [Google Scholar]
  19. a Lu K.; Duan L.; Xu B.; Yin W.; Wu D.; Zhao Y.; Gong P. Facile synthesis of 3-amino-5-aryl-1,2,4-oxadiazoles via PIDA-mediated intramolecular oxidative cyclization. RSC Adv. 2016, 6, 54277–54280. 10.1039/C6RA08871F. [DOI] [Google Scholar]; b Shang X.–X.; Vu H.–M.; Li X.–Q. One-Pot Synthesis of 2-Arylbenzoxazinones from 2-Arylindoles with (Diacetoxyiodo)benzene as the Sole Oxidant. Synthesis 2018, 50, 377–383. 10.1055/s-0036-1590933. [DOI] [Google Scholar]
  20. UV/vis spectroscopy studies were supported this trend. In detail, please see the Supporting Information (Supporting Figure 1).
  21. Maiti S.; Alam M. T.; Mal P. Soft–Hard Acid–Base-Controlled C–H Trifluoroethoxylation and Trideuteriomethoxylation of Anilides. Asian J. Org. Chem. 2018, 7, 715–719. 10.1002/ajoc.201800069. [DOI] [Google Scholar]
  22. In UV/vis experiment of the mixture of Iodine (III) reagents (PIDA and PIFA) and sulfide 1 in DMF, we found that PIFA displayed a different peak pattern with PIDA case. Please see the Supporting Information (Supporting Figure 2)
  23. CCDC 1974248 (2a) contain the Supporting crystallographic data for this paper. These data are provided free of by The Cambridge Crystallographic Centre. For the reported crystal structure of N-cyano sulfilimine, see; a ref. 5a; b Zhou S.; Zhou S.; Xie Y.–T.; Jin R.–Y.; Meng X.–D.; Zhang D.–K.; Hua X.–W.; Liu M.; Wu C.–C.; Xiong L.–X.; Zhao Y.; Li Z.–M. The exploration of chiral N-cyano sulfiliminyl dicarboxamides on insecticidal activities. Chin. Chem. Lett. 2017, 28, 1499–1504. 10.1016/j.cclet.2017.02.021. [DOI] [Google Scholar]
  24. a Guo S.–R.; Kumar P. S.; Yuan Y.–Q.; Yang M.–H. Gold-Catalyzed, Iodine(III)-Mediated Direct Acyloxylation of the Unactivated C(sp3)–H Bonds of Methyl Sulfides. Eur. J. Org. Chem. 2016, 4260–4264. 10.1002/ejoc.201600632. [DOI] [Google Scholar]; b Zhu D.; Chang D.; Gan S.; Shi L. Direct α-acyloxylation of organic sulfides with the hypervalent (diacyloxyiodo)benzene/tetra-n-butylammonium bromide (TBAB) reagent combination. RSC Adv. 2016, 6, 27983–27987. 10.1039/C6RA01799A. [DOI] [Google Scholar]
  25. For the 1H NMR study of the mixture of 2,2,2-trifluoroacetamide and PIDA in deuterated DMF, we confirmed that the proton peak corresponding to NH2C(O)CF3 unchanged for over 6 h
  26. a SHIMADZU Technical information (UV). www.Shimadzu.com/an/uv/support/ap/apl.html.; b Barlin G. B.; Riggs N. V. The reaction of phenyl iodosoacetate with N-arylacetamides. J. Chem. Soc. 1954, 3125–3128. 10.1039/jr9540003125. [DOI] [Google Scholar]
  27. In details, please see the Supporting Information (Supporting Figure 3 and Table 1)

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ao0c01086_si_001.pdf (3.4MB, pdf)

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