Catalytic Synthesis of Sulfoximines using Copper(II) Salts

Abstract

The reaction of PhI=NTs with sulfoxides in the presence of catalytic amounts of copper(II) salts afforded the corresponding N-tosylsulfoximines in high yield. This method is highly tolerant to reaction conditions (no need of distilled solvents and/or inert atmospheres) and allowed the formation of previously unknown acetylenic sulfoximines with complete retention of configuration at sulfur.

asymmetric synthesis - catalysis - copper - sulfoxides - sulfur

References

1 Johnson CR. Aldrichimica Acta  1985,  18:  3 

2 Reggelin M. Zur C. Synthesis  2000,  1 

3 Bolm C. Kaufmann D. Zehnder M. Neuburger M. Tetrahedron Lett.  1996,  37:  3985 

4 Bolm C. Simic O. J. Am. Chem. Soc.  2001,  123:  3830 

5 Evans DA. Bilodeau MT. Faul MM. J. Am. Chem. Soc.  1994,  116:  2742 

6a Muller JFK. Vogt P. Tetrahedron Lett.  1998,  39:  4805 

6b For iron-mediated related work, see: Bach T. Körber C. Eur. J. Org. Chem.  1999,  1033 

7 Bolm C. Muniz K. Aguilar N. Kesselgruber M. Raabe G. Synthesis  1999,  1251 

8 Bolm C. Kesselgruber M. Muniz K. Raabe G. Organometallics  2000,  19:  1648 

9 Takada H. Nishibayashi Y. Ohe K. Uemura S. Baird CP. Sparey TJ. Taylor PC. J. Org. Chem.  1997,  62:  6512 

10

Representative Procedure: Ethyl p-tolylsulfoxide (0.5 mmol; 1 equiv; 84 mg) was added to a solution of Cu(OTf)₂ (0.5 mmol; 10 mol%; 18 mg) in MeCN (3 mL) at r.t. PhI=NTs (0.55 mmol; 1.1 equiv; 205 mg) was then dropped in one batch. The reaction was monitored by rapid disappearance of the yellowish powder from the reaction mixture, which turned homogeneous and green after two minutes. MeCN was removed in vacuo and the crude material was purified by FC on silicagel (10 g; hexane-AcOEt 70/30) to yield sulfoximine 2a (163 mg; 96%). 2a: C₁₆H₁₉O₃S₂, MW = 337.45, white solid, mp 79-81 °C. IR(neat): 3000, 2940, 2220, 1575 cm^-1. ^¹ H NMR (400 MHz, CDCl₃): δ = 7.86 (d, J = 7.9 Hz, 4 H arom.); 7.41 (d, J = 8.1 Hz, 2 H arom.); 7.27 (d, J = 8.1 Hz, 2 H arom.); 3.53 (q, J = 7.4 Hz, 2 H); 2.48 (s, 3 H); 2.41 (s, 3 H); 1.28 (d, J = 7.4 Hz, 3 H). ^¹³ C NMR (50 MHz, CDCl₃): δ = 145.4 (s), 142.4 (s), 140.7 (s), 132.3 (s), 130.0 (d), 129.0 (d), 128.2 (d), 126.4 (d), 52.7 (t), 21.5 (q), 21.3 (q), 7.2 (q). Anal. Calcd for C₁₆H₁₉O₃S₂: C, 56.95; H, 5.67; N, 4.15. Found: C, 56.79; H, 5.82; N, 4.27.

11

The sulfoximines were separated on a CHIRALCEL OJ column (Heptane-i-PrOH 88/12; 0.3 mLmin^-1; p = 15 bar) and compared to racemic samples. Sulfoxides with ee > 98% led to sulfoximines with ee > 98%.

12

When submitted to our conditions, (R)-methyl-p-tolyl sulfoxide (ee > 98%) yielded the corresponding (-) sulfoximine (97%, ee > 98%), implying an (R) absolute configuration at sulfur (Johnson, C. R.; Schroeck, C. W. J. Am. Chem. Soc. 1973, 95, 7418; we obtained the same specific rotation as the authors. This delivers additional evidence for a good ee). The reaction thus proceeds with retention of configuration.

13 Handy ST. Czopp M. Org. Lett.  2001,  3:  1423