Metal-Free Synthesis of N-Cyano-Substituted Sulfilimines and Sulfoximines

Abstract

Starting from the corresponding sulfides, N-cyano sulfoximines can easily be accessed under metal-free conditions via the corresponding N-cyano-substituted sulfilimines. The reaction sequence involves a sulfide imination with cyanogen amide in presence of a base and N-bromosuccinimide (NBS) followed by an m-chloroperoxybenzoic acid (MCPBA) mediated oxidation of the resulting sulfilimine intermediates.

Introduction

Sulfoximines are of interest owing to their biological activity [¹] and their potential in asymmetric synthesis. [²] [³] Two main routes are generally employed for their preparation. The first starts with a sulfide oxidation followed by an imination of the resulting sulfoxide. Alternatively, sulfoximines can be accessed through a sulfide imination/sulfilimine oxidation sequence. [²] Most sulfur imination methods rely on the use of metal catalysts. [4] [5] Recently, we developed a metal-free approach towards N-cyano sulfilimines, [6] which are attractive intermediates for the preparation of synthetically relevant N-cyano-substituted sulfoximines. [7] Important features of this protocol were the use of simple cyanogen amide as nitrogen source in combination with standard oxidizing agents such as N-bromosuccinimide (NBS) or I₂, which avoids the potential dangers associated with the previously applied iodobenzene diacetate or related iodine reagents of higher oxidation state. [8] Here, we demonstrate that this approach is also applicable for the preparation of multi-gram quantities of N-cyano sulfoximines (Scheme  [¹] ).

Scope and Limitations

As shown in Table  [¹] , the imination of various sulfides 1 with a combination of cyanogen amide and NBS in the presence of potassium tert-butoxide (t-BuOK) proceeded well in methanol at room temperature, providing N-cyano sulfilimines 2 in yields ranging from 75 to 95%. [9] Hence, compared to our previously reported results, the scale-up (up to 24-fold) did not significantly affect the reaction outcome.

Table 1 Iminations of Sulfides 1

Entry	R¹	R²	Product	Yield of 2 (%)
1	Ph	Me	2a	93
2	Bn	Me	2b	80
3	Ph	Ph	2c	95
4	4-O2NC6H4	Me	2d	75
5	4-MeOC6H4	Me	2e	89

Next, oxidations of sulfilimines 2 with m-chloroperoxybenzoic acid (MCPBA) in ethanol to provide N-cyano sulf­oximines 3 were investigated (Table  [²] ). [¹0] Also in this case, the scale-up had no major influence on the yields of the desired products, and N-cyano sulfoximines 3 were obtained in up to 96% yield.

Table 2 Oxidation of N-Cyano Sulfilimines 2

Entry	N-Cyano sulfilimine	Product	Yield of 3 (%)
1	2a	3a	76
2	2b	3b	60
3	2c	3c	86
4	2d	3d	96
5	2e	3e	77

Finally it should be noted that the free NH-sulfoximines 4 can easily be prepared from the corresponding N-cyano sulfoximines 3 by treatment with either diluted H₂SO₄ [8b] or trifluoroacetic anhydride (TFAA), followed by addition of K₂CO₃ (Scheme  [²] ). [6] The latter reaction sequence is a two-step process that proceeds via the synthetically interesting trifluoroacetyl-protected sulfoximines 5, which can also be isolated in good yields. [6] This reaction was demonstrated for sulfoximine 3a, which was converted into NH-sulfoximine 4a. In this case, both methods gave almost identical yields (64 and 63%, respectively) in gram-scale reactions.

In summary, we have demonstrated gram-scale syntheses of N-cyano-protected sulfilimines and sulfoximines using simple and readily available reagents under straightforward reaction conditions. We expect this protocol to find applications in the preparation of biologically relevant products such as agrochemicals.

All starting materials were purchased from commercial suppliers and used without further purification unless stated otherwise. The reactions were performed in air. All products were known and their full characterization was reported before. [5d] Here, only the ^¹H and ^¹³C NMR data are listed.

N -Cyano Methyl Phenyl Sulfilimine (2a)

A mixture of methyl phenyl sulfide (24 mmol, 3.0 g), cyanogen amide (31 mmol, 1.3 g) and t-BuOK (29 mmol, 3.2 g) were dissolved in MeOH (72 mL). NBS (36 mmol, 6.4 g) was added, and the reaction mixture was stirred for 1.5 h. The solvent was evaporated using a rotatory evaporator, sat. sodium thiosulfate (100 mL) was added, and the mixture was extracted with CH₂Cl₂ (3 × 60 mL). The combined organic layers were washed with H₂O and dried over anhydrous MgSO₄. Evaporation of the solvent in vacuo followed by purification by flash column chromatography (CH₂Cl₂-acetone, 9:1) afforded 2a.

Yield: 3.7 g (93%); colorless oil.

^¹H NMR (300 MHz, CDCl₃): δ = 7.82-7.77 (m, 2 H), 7.67-7.55 (m, 2 H), 3.02 (s, 3 H).

^¹³C NMR (75 MHz, CDCl₃): δ = 135.8 (C), 132.9 (CH), 130.1 (2 × CH), 125.7 (2 × CH), 120.5 (CN), 36.4 (CH₃).

N -Cyano Benzyl Methyl Sulfilimine (2b)

Produced as for the synthesis of 2a using: benzyl methyl sulfide (7.3 mmol, 1.0 g), cyanogen amide (9.5 mmol, 0.4 g), t-BuOK (8.7 mmol, 0.8 g), MeOH (22 mL), and NBS (10.9 mmol, 1.9 g). The product was purified by flash column chromatography (CH₂Cl₂-acetone­, 6:1→1:1) to give 2b.

Yield: 1.04 g (80%); white solid.

^¹H NMR (300 MHz, CDCl₃): δ = 7.47-7.42 (m, 3 H), 7.40-7.34 (m, 2 H), 4.43 and 4.19 (AB system, J = 12.8 Hz, 2 H), 2.73 (s, 3 H).

^¹³C NMR (75 MHz, CDCl₃): δ = 130.1 (2 × CH), 129.6 (CH), 129.5 (2 × CH), 127.6 (C), 119.5 (CN), 55.4 (CH₂), 31.2 (CH₃).

N -Cyano Diphenyl Sulfilimine (2c)

Produced as for the synthesis of 2a using: diphenyl sulfide (16.1 mmol, 3.0 g), cyanogen amide (20.9 mmol, 0.9 g), t-BuOK (19.3 mmol, 2.2 g), MeOH (48 mL), and NBS (24.2 mmol, 4.3 g). The mixture was stirred for 2 h (instead of 1.5 h). The product was purified by flash column chromatography (CH₂Cl₂-acetone, 9:1) to give 2c.

Yield: 3.4 g (95%); white solid.

^¹H NMR (400 MHz, CDCl₃): δ = 7.72-7.53 (m, 10 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 135.7 (2 × C), 132.9 (2 × CH), 130.1 (4 × CH), 127.4 (4 × CH), 120.6 (CN).

N -Cyano Methyl 4-Nitrophenyl Sulfilimine (2d)

Produced as for the synthesis of 2c using: methyl 4-nitrophenyl sulfide (5.91 mmol, 1.0 g), cyanogen amide (7.7 mmol, 0.3 g), t-BuOK (7.1 mmol, 0.8 g), MeOH (18 mL), and NBS (8.9 mmol, 1.6 g). CH₂Cl₂ (3 × 65 mL) was used for extraction of the aqueous layer. The product was purified by flash column chromatography (CH₂Cl₂-acetone, 9:1) to give 2d.

Yield: 0.9 g (75%); pale yellow solid.

^¹H NMR (300 MHz, CD₃OD): δ = 8.53 (br d, J = 9.2 Hz, 2 H), 8.18 (br d, J = 9.2 Hz, 2 H), 3.21 (s, 3 H).

^¹³C NMR (75 MHz, CD₃OD): δ = 152.1 (C), 144.5 (C), 128.8 (2 × CH), 126.3 (2 × CH), 121.9 (CN), 37.2 (CH₃).

N -Cyano Methyl 4-Methoxyphenyl Sulfilimine (2e)

Produced as for the synthesis of 2a using: methyl 4-methoxyphenyl sulfide (6.5 mmol, 1.0 g), cyanogen amide (8.4 mmol, 0.35 g), t-BuOK (7.8 mmol, 0.9 g), MeOH (20 mL), and NBS (9.7 mmol, 1.7 g). CH₂Cl₂ (3 × 65 mL) was used for extraction of the aqueous layer. The product was purified by flash column chromatography (CH₂Cl₂-acetone, 9:1→2:1) to give 2e.

Yield: 1.1 g (89%); light, pale yellow solid.

^¹H NMR (300 MHz, CD₃OD): δ = 7.87 (d, J = 9.0 Hz, 2 H), 7.22 (d, J = 9.0 Hz, 2 H), 3.93 (s, 3 H), 3.12 (s, 3 H).

^¹³C NMR (75 MHz, CD₃OD): δ = 163.8 (C), 128.5 (2 × CH), 126.2 (C), 121.3 (CN), 115.4 (2 × CH), 55.0 (CH₃), 34.8 (CH₃).

N -Cyano Methyl Phenyl Sulfoximine (3a)

To a stirred solution of sulfilimine 2a (22.5 mmol, 3.7 g) in EtOH (60 mL), K₂CO₃ (67.6 mmol, 9.3 g) and MCPBA (33.8 mmol, 5.8 g) were added at 0 ˚C. The reaction mixture was allowed to warm to r.t. and stirring was continued for 1.5 h. The solvent was removed under vacuo, and H₂O (150 mL) was added. The resulting mixture was extracted with CH₂Cl₂ (3 × 65 mL) and the combined organic phases were dried over anhydrous MgSO₄ and filtered. Evaporation of the solvent in vacuo followed by flash column chromatography (acetone-pentane, 1:3) gave 3a.

Yield: 3.1 g (76%); white solid.

^¹H NMR (300 MHz, CDCl₃): δ = 8.04-7.98 (m, 2 H), 7.79 (tt, J = 7.4, 1.2 Hz, 1 H), 7.73-7.66 (m, 2 H), 3.35 (s, 3 H).

^¹³C NMR (75 MHz, CDCl₃): δ = 136.0 (C), 135.5 (CH), 130.3 (2 × CH), 127.9 (2 × CH), 111.8 (CN), 44.8 (CH₃).

N -Cyano Benzyl Methyl Sulfoximine (3b)

Produced as for the synthesis of 3a using: sulfilimine 2b (5.8 mmol, 1.04 g), EtOH (60 mL), K₂CO₃ (17.5 mmol, 2.4 g) and MCPBA (8.7 mmol, 1.5 g). Flash column chromatography (EtOAc-pentane, 4:1) gave 3b.

Yield: 0.7 g (60%); white solid.

^¹H NMR (300 MHz, CDCl₃): δ = 7.51-7.43 (m, 5 H), 4.62 (s, 2 H), 3.01 (s, 3 H).

^¹³C NMR (75 MHz, CDCl₃): δ = 131.2 (2 × CH), 130.5 (CH), 129.3 (2 × CH), 125.9 (C), 112.2 (CN), 61.8 (CH₂), 38.6 (CH₃).

N -Cyano Diphenyl Sulfoximine (3c)

Produced as for the synthesis of 3a using: sulfilimine 2c (15.0 mmol, 3.4 g), EtOH (60 mL), K₂CO₃ (45.1 mmol, 6.2 g) and MCPBA­ (22.5 mmol, 3.9 g). The mixture was stirred for 2 h (instead of 1.5 h). Flash column chromatography (EtOAc-pentane, 2:1) gave 3c.

Yield: 3.1 g (86%); white solid.

^¹H NMR (400 MHz, CDCl₃): δ = 8.03 (dd, J = 7.1, 1.7 Hz, 2 H), 7.69 (tt, J = 7.1, 1.4 Hz, 4 H), 7.61 (tt, J = 7.1, 1.7 Hz, 4 H).

^¹³C NMR (100 MHz, CDCl₃): δ = 137.3 (2 × C), 134.7 (2 × CH), 130.0 (4 × CH), 127.9 (4 × CH), 111.9 (CN).

N -Cyano Methyl 4-Nitrophenyl Sulfoximine (3d)

Produced as for the synthesis of 3a using: sulfilimine 2d (4.3 mmol, 0.9 g), EtOH (60 mL), K₂CO₃ (12.9 mmol, 1.8 g) and MCPBA (6.5 mmol, 1.1 g). The mixture was stirred for 2.5 h (instead of 1.5 h). Flash column chromatography (EtOAc-pentane, 1:4→EtOAc) gave 3d.

Yield: 0.9 g (96%); pale yellow solid.

^¹H NMR (300 MHz, DMSO-d ₆): δ = 8.55 (br d, J = 8.8 Hz, 2 H), 8.32 (br d, J = 8.8 Hz, 2 H), 3.30 (s, 3 H).

^¹³C NMR (75 MHz, DMSO-d ₆): δ = 151.3 (C), 141.8 (C), 129.6 (2 × CH), 125.1 (2 × CH), 111.6 (CN), 42.1 (CH₃).

N -Cyano Methyl 4-Methoxyphenyl Sulfoximine (3e)

Produced as for the synthesis of 3c using: sulfilimine 2e (5.7 mmol, 1.1 g), EtOH (60 mL), K₂CO₃ (17.0 mmol, 2.3 g) and MCPBA (8.6 mmol, 1.5 g). Flash column chromatography (EtOAc-pentane, 1:4→EtOAc) gave 3e.

Yield: 0.9 g (77%); white solid.

^¹H NMR (300 MHz, CD₃OD): δ = 7.97 (br d, J = 9.1 Hz, 2 H), 7.23 (br d, J = 9.1 Hz, 2 H), 3.91 (s, 3 H), 3.47 (s, 3 H).

^¹³C NMR (75 MHz, CD₃OD): δ = 165.3 (C), 130.1 (2 × CH), 126.8 (C), 115.1 (2 × CH), 112.7 (CN), 55.2 (CH₃), 43.4 (CH₃).

N H-Methyl Phenyl Sulfoximine (4a)

Method A: To sulfoximine 3a (1.0 g, 5.6 mmol), aq H₂SO₄ (50%, 25 mL) was added. The mixture was heated at reflux for 2 h and then allowed to cool to r.t. After neutralization with 50% NaOH the mixture was extracted with CH₂Cl₂ (3 × 50 mL), the combined organic layers were dried over anhydrous MgSO₄ and the solvent was removed under reduced pressure. Purification by flash column chromatography (EtOAc-acetone, 5:1) gave 4a.

Yield: 0.6 g (64%) white solid.

^¹H NMR (300 MHz, CDCl₃): δ = 8.06-7.98 (m, 2 H), 7.66-7.52 (m, 3 H), 3.10 (s, 3 H, CH₃), 2.86 (br s, 1 H, NH).

^¹³C NMR (75 MHz, CDCl₃): δ = 132.9 (CH), 129.1 (2 × CH), 127.6 (2 × CH), 46.1 (CH₃).

Method B: To a stirred solution of sulfoximine 3a (5.6 mmol, 1.0 g) in CH₂Cl₂ (100 mL) at 0 ˚C, TFAA (2.3 mL, 16.6 mmol) was added. The mixture was allowed to react at r.t. until most of the starting material was consumed (monitored by TLC). Then, the reaction mixture was concentrated, diluted with MeOH (40 mL) and treated with K₂CO₃ (27.7 mmol, 3.8 g). The reaction was allowed to react at r.t. until the starting material was consumed (monitored by TLC). The solvent was then removed under reduced pressure and H₂O (100 mL) was added. The resulting mixture was extracted with CH₂Cl₂ (3 × 50 mL) and the organic layer was then dried over anhydrous MgSO₄ and filtered. Evaporation of the solvent in vacuo followed by flash column chromatography (EtOAc→EtOAc-acetone, 5:1) gave 4a.

Yield: 0.5 g (63%); white solid.

Acknowledgment

This work was supported by the Fonds der Chemischen Industrie and, in part, by a grant from the German-Israeli Foundation (GIF) for scientific research and development.

References

• For selected recent examples, see:
• 1a Walker DP. Zawistoski MP. McGlynn MA. Li J.-C. Kung DW. Bonnette PC. Baumann A. Buckbinder L. Houser JA. Boer J. Mistry A. Han S. Xing L. Guzman-Perez A. Bioorg. Med. Chem. Lett.  2009,  19:  3253 
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• 1d Jautelat R, Lücking U, Siemeister G, Schulze J, and Lienau P. inventors; (Bayer Schering Pharma AG) 046035  A1. 
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• 2a Reggelin M. Zur C. Synthesis  2000,  1 
• 2b Harmata M. Chemtracts  2003,  16:  660 
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• 2c Okamura H. Bolm C. Chem. Lett.  2004,  33:  482 
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• 2d Bentley R. Chem. Soc. Rev.  2005,  34:  609 
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• 2e Worch C. Mayer AC. Bolm C. In Organosulfur Chemistry in Asymmetric Synthesis   Toru T. Bolm C. Wiley-VCH; Weinheim: 2008.  p.209 
• For recent applications of sulfoximines as chiral ligands in metal catalysis, see:
• 3a Frings M. Atodiresei I. Wang Y. Runsink J. Raabe G. Bolm C. Chem. Eur. J.  2010,  16:  4577 
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• 3b Frings M. Goedert D. Bolm C. Chem. Commun.  2010, DOI: 10.1039/C0CC00996B; and references therein
• For Cu catalysis, see:
• 4a Kwart H. Kahn AA. J. Am. Chem. Soc.  1967,  89:  1950 
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• 4b Müller JFK. Vogt P. Tetrahedron Lett.  1998,  39:  4805 
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• 4c Lacôte E. Amatore M. Fensterbank L. Malacria M. Synlett  2002,  116 
• For Rh catalysis, see:
• 4d Okamura H. Bolm C. Org. Lett.  2004,  6:  1305 
  Search in Google Scholar
• For Ag catalysis, see:
• 4e Cho GY. Bolm C. Org. Lett.  2005,  7:  4983 
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• For Fe catalysis, see:
• 4f Bach T. Körber C. Tetrahedron Lett.  1998,  39:  5015 
  Search in Google Scholar
• 4g Bach T. Körber C. Eur. J. Org. Chem.  1999,  64:  1033 
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• 4h García Mancheño O. Bolm C. Org. Lett.  2006,  8:  2349 
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• 4i Bolm C. García Mancheño O. Chem. Eur. J.  2007,  13:  6674 
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• 4j Bolm C. García Mancheño O. Dallimore J. Plant A. Org. Lett.  2009,  11:  2429 
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• For metal-free sulfur iminations, see:
• 5a Cho GY. Bolm C. Tetrahedron Lett.  2005,  46:  8007 
  Search in Google Scholar
• 5b Siu T. Picard CJ. Yudin AK. J. Org. Chem.  2005,  70:  932 
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• 5c Karabuga S. Kazaz C. Kilic H. Ulukanli S. Celik A. Tetrahedron Lett.  2005,  46:  5225 
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• 5d Krasnova LB. Hili RM. Chernoloz OV. Yudin AK. ARKIVOC  2005,  (iv):  26 
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• 5e García Mancheño O. Bolm C. Org. Lett.  2007,  9:  2951 
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• 5f Ochiai M. Naito M. Miyamoto K. Hayashi S. Nakanishi W. Chem. Eur. J.  2010,  in press, DOI: 10.1002/chem.201000759 
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  CrossrefSearch in Google Scholar
• 7a Huang JX, Rogers RB, Orr N, Sparks TC, Gifford JM, Loso MR, Zhu Y, and Meade T. inventors; (Dow AgroSciences) WO 149134  A1. Various N-cyano sulfoximines are of interest as agrochemicals. A prominent example is the sap-feeding insecticide Sulfoxaflor, which is scheduled for launch in 2012 by Dow AgroSciences. For details, see:
• 7b Schade M, Grimm C, Faerber M, Müller K, and Campbell S. inventors; (Syngenta) WO  040623. For a recent report on pesticidal combinations containing Sulfoxaflor, see:
• For previous syntheses of sulfilimines and sulfoximines with N-cyano groups, see:
• 8a Swern D. Ikeda I. Whitfield GF. Tetrahedron Lett.  1972,  2635 
• 8b Stoss P. Satzinger G. Tetrahedron Lett.  1973,  267 
• 8c Hutchins MGK. Swern D. Tetrahedron Lett.  1981,  22:  4599 
  Search in Google Scholar
• 8d Kemp JEG. Ellis D. Closier MD. Tetrahedron Lett.  1979,  3781 
• 8e Zhu Y, Rogers RB, and Huang JX. inventors; (Dow AgroSciences) US 0228027  A1. 

Using I₂ instead of NBS under those conditions led to the desired products in lower yields.

Attempting to use other oxidants such as KMnO₄ for the sulfilimine oxidations led to lower sulfoximine yields.

References

• For selected recent examples, see:
• 1a Walker DP. Zawistoski MP. McGlynn MA. Li J.-C. Kung DW. Bonnette PC. Baumann A. Buckbinder L. Houser JA. Boer J. Mistry A. Han S. Xing L. Guzman-Perez A. Bioorg. Med. Chem. Lett.  2009,  19:  3253 
  Search in Google Scholar
• 1b García Mancheño O. Dallimore J. Plant A. Bolm C. Adv. Synth. Catal.  2010,  352:  309 
  Search in Google Scholar
• 1c Jeschke P, Thielert W, and Hungenberg H. inventors; WO 022897  A2.  (Bayer CropScience AG)
• 1d Jautelat R, Lücking U, Siemeister G, Schulze J, and Lienau P. inventors; (Bayer Schering Pharma AG) 046035  A1. 
• For reviews, see:
• 2a Reggelin M. Zur C. Synthesis  2000,  1 
• 2b Harmata M. Chemtracts  2003,  16:  660 
  Search in Google Scholar
• 2c Okamura H. Bolm C. Chem. Lett.  2004,  33:  482 
  Search in Google Scholar
• 2d Bentley R. Chem. Soc. Rev.  2005,  34:  609 
  Search in Google Scholar
• 2e Worch C. Mayer AC. Bolm C. In Organosulfur Chemistry in Asymmetric Synthesis   Toru T. Bolm C. Wiley-VCH; Weinheim: 2008.  p.209 
• For recent applications of sulfoximines as chiral ligands in metal catalysis, see:
• 3a Frings M. Atodiresei I. Wang Y. Runsink J. Raabe G. Bolm C. Chem. Eur. J.  2010,  16:  4577 
  Search in Google Scholar
• 3b Frings M. Goedert D. Bolm C. Chem. Commun.  2010, DOI: 10.1039/C0CC00996B; and references therein
• For Cu catalysis, see:
• 4a Kwart H. Kahn AA. J. Am. Chem. Soc.  1967,  89:  1950 
  Search in Google Scholar
• 4b Müller JFK. Vogt P. Tetrahedron Lett.  1998,  39:  4805 
  Search in Google Scholar
• 4c Lacôte E. Amatore M. Fensterbank L. Malacria M. Synlett  2002,  116 
• For Rh catalysis, see:
• 4d Okamura H. Bolm C. Org. Lett.  2004,  6:  1305 
  Search in Google Scholar
• For Ag catalysis, see:
• 4e Cho GY. Bolm C. Org. Lett.  2005,  7:  4983 
  Search in Google Scholar
• For Fe catalysis, see:
• 4f Bach T. Körber C. Tetrahedron Lett.  1998,  39:  5015 
  Search in Google Scholar
• 4g Bach T. Körber C. Eur. J. Org. Chem.  1999,  64:  1033 
  Search in Google Scholar
• 4h García Mancheño O. Bolm C. Org. Lett.  2006,  8:  2349 
  Search in Google Scholar
• 4i Bolm C. García Mancheño O. Chem. Eur. J.  2007,  13:  6674 
  Search in Google Scholar
• 4j Bolm C. García Mancheño O. Dallimore J. Plant A. Org. Lett.  2009,  11:  2429 
  Search in Google Scholar
• For metal-free sulfur iminations, see:
• 5a Cho GY. Bolm C. Tetrahedron Lett.  2005,  46:  8007 
  Search in Google Scholar
• 5b Siu T. Picard CJ. Yudin AK. J. Org. Chem.  2005,  70:  932 
  Search in Google Scholar
• 5c Karabuga S. Kazaz C. Kilic H. Ulukanli S. Celik A. Tetrahedron Lett.  2005,  46:  5225 
  Search in Google Scholar
• 5d Krasnova LB. Hili RM. Chernoloz OV. Yudin AK. ARKIVOC  2005,  (iv):  26 
  Search in Google Scholar
• 5e García Mancheño O. Bolm C. Org. Lett.  2007,  9:  2951 
  Search in Google Scholar
• 5f Ochiai M. Naito M. Miyamoto K. Hayashi S. Nakanishi W. Chem. Eur. J.  2010,  in press, DOI: 10.1002/chem.201000759 
• 6 García Mancheño O. Bistri O. Bolm C. Org. Lett.  2007,  9:  3809 
  CrossrefSearch in Google Scholar
• 7a Huang JX, Rogers RB, Orr N, Sparks TC, Gifford JM, Loso MR, Zhu Y, and Meade T. inventors; (Dow AgroSciences) WO 149134  A1. Various N-cyano sulfoximines are of interest as agrochemicals. A prominent example is the sap-feeding insecticide Sulfoxaflor, which is scheduled for launch in 2012 by Dow AgroSciences. For details, see:
• 7b Schade M, Grimm C, Faerber M, Müller K, and Campbell S. inventors; (Syngenta) WO  040623. For a recent report on pesticidal combinations containing Sulfoxaflor, see:
• For previous syntheses of sulfilimines and sulfoximines with N-cyano groups, see:
• 8a Swern D. Ikeda I. Whitfield GF. Tetrahedron Lett.  1972,  2635 
• 8b Stoss P. Satzinger G. Tetrahedron Lett.  1973,  267 
• 8c Hutchins MGK. Swern D. Tetrahedron Lett.  1981,  22:  4599 
  Search in Google Scholar
• 8d Kemp JEG. Ellis D. Closier MD. Tetrahedron Lett.  1979,  3781 
• 8e Zhu Y, Rogers RB, and Huang JX. inventors; (Dow AgroSciences) US 0228027  A1. 

Using I₂ instead of NBS under those conditions led to the desired products in lower yields.

Attempting to use other oxidants such as KMnO₄ for the sulfilimine oxidations led to lower sulfoximine yields.