Sulfur Ylide Mediated Three-Component
Aziridination and Epoxidation Reactions Using Vinyl Sulfonium
Salts

Christoforos G. Kokotos; Eoghan M. McGarrigle; Varinder K. Aggarwal

doi:10.1055/s-2008-1078252

LETTER

Sulfur Ylide Mediated Three-Component Aziridination and Epoxidation Reactions Using Vinyl Sulfonium Salts

Christoforos G. Kokotos, Eoghan M. McGarrigle, Varinder K. Aggarwal*
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
Fax: +44(117)9298611; e-Mail: v.aggarwal@bristol.ac.uk;

Abstract

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Abstract

Coupling of diphenylvinyl sulfonium triflate with nucleophiles and either aldehydes or imines gives epoxides and aziridines, respectively, in a three-component reaction. cis-Aziridines could be formed in good diastereomeric ratio, and the selectivity was correlated to the reactivity of the imine. This represents the first study of cis/trans selectivity in the reactions of imines with nonstabilized sulfur ylides.

Key words

sulfur ylides - epoxidations - aziridinations - multicomponent reactions - vinyl sulfonium salts

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References

References and Notes

Reviews:

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There is one isolated report of an epoxidation reaction of a butadienylsulfonium salt with a β-keto ester and aldehyde. See:

4a Rowbottom MW. Mathews N. Gallagher T. J. Chem. Soc., Perkin Trans. 1 1998, 3927

For a related example using vinyl selenonium salts, see:

4b Watanabe Y. Ueno Y. Toru T. Bull. Chem. Soc. Jpn. 1993, 66: 2042

5 Corey EJ. Oppolzer W. J. Am. Chem. Soc. 1964, 86: 1899

Nucleophiles with two acidic protons on the same atom have been shown to react with vinyl sulfonium salts to give three-membered rings:

6a Gosselck J. Béress L. Schenk H. Angew. Chem., Int. Ed. Engl. 1966, 5: 596 ; Angew. Chem. 1966, 78, 606

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6f Batty JW. Howes PD. Stirling CJM. J. Chem. Soc., Perkin Trans. 1 1973, 65 ; ref. 6b

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7b Aggarwal VK. Stenson RA. Jones RVH. Fieldhouse R. Blacker J. Tetrahedron Lett. 2001, 42: 1587

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8a McGarrigle EM. Myers EL. Illa O. Shaw MA. Riches SL. Aggarwal VK. Chem. Rev. 2007, 107: 5841

8b Hou XL. Wu J. Fan RH. Ding CH. Luo ZB. Dai LX. Synlett 2006, 181

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8d Aggarwal VK. Badine DM. Moorthie VA. In Aziridines and Epoxides in Asymmetric Synthesis Yudin AK. Wiley-VCH; Weinheim: 2006. Chap. 1.

Only cis-aziridine was obtained in the reaction of(dimethylamino)-p-tolyloxosulfonium ethylide with PhCH=NPh, see:

8e Johnson CR. Janiga ER. J. Am. Chem. Soc. 1973, 95: 7692

9 Aggarwal VK. Charmant JPH. Ciampi C. Hornby JM. O’Brien CJ. Hynd G. Parsons R. J. Chem. Soc., Perkin Trans. 1 2001, 3159

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12

The products were characterized by NMR, IR, MS, and mp (where appropriate). Satisfactory elemental analyses and/or HRMS were obtained for all compounds. Full details and spectra are available from the authors.

13

N ,4-Dimethyl- N -{[1-(toluene-4-sulfonyl)-3-phenyl-2-aziridinyl]methyl}benzenesulfonamide (Table 2, Entry 2) cis-Isomer as a colourless oil; R _f = 0.40 (EtOAc-PE, 3:7). IR (film): 1598 (Ar), 1330 (SO₂), 1160 (SO₂) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.86 (2 H, d, J = 8.3 Hz, ArH), 7.50 (2 H, d, J = 8.3 Hz, ArH), 7.35 (2 H, d, J = 8.3 Hz, ArH), 7.27-7.16 (7 H, m, ArH), 3.93 (1 H, d, J = 7.0 Hz, NCHPh), 3.25-3.14 (2 H, m, NCHH and NCHCH₂), 2.53 (1 H, dd, J = 14.3, 7.0 Hz, NCHH), 2.44 (6 H, s, 2 × CH₃), 2.38 (3 H, s, CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 145.0 (C), 143.5 (C), 136.2 (C), 135.9 (C), 132.0 (C), 130.0 (CH), 129.9 (CH), 129.7 (CH), 128.6 (CH), 128.3 (CH), 127.4 (CH), 127.3 (CH), 47.6 (CH₂), 44.4 (CH), 44.1 (CH), 35.4 (CH₃), 21.7 (CH₃), 21.5 (CH₃). MS (CI): m/z (%) = 471 (14) [MH⁺], 198 (100) [Ts(Me)NCH₂ ⁺]; trans-isomer (obtained as a mixture with cis-isomer) as a colorless oil; R _f = 0.40 (EtOAc-PE, 3:7). IR (film): ν_max = 1599 (Ar), 1332 (SO₂), 1161 (SO₂) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.77 (2 H, d, J = 8.3 Hz, ArH), 7.69 (2 H, d, J = 8.3 Hz, ArH), 7.31 (2 H, d, J = 8.3 Hz, ArH), 7.26-7.19 (7 H, m, ArH), 3.85 (1 H, d, J = 3.8 Hz, NCHPh), 3.55 (1 H, dd, J = 14.6, 8.6 Hz, NCHH), 3.03 (1 H, ddd, J = 8.6, 8.6, 3.8 Hz, NCHCH₂N), 2.43 (6 H, s, 2 × CH₃), 2.42-2.38 (4 H, m, NCHH and CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 144.9 (C), 143.6 (C), 136.2 (C), 134.0 (C), 132.0 (C), 129.9 (CH), 129.8 (CH), 128.6 (CH), 128.5 (CH), 127.4 (CH), 127.3 (CH), 126.9 (CH), 49.6 (CH), 49.0 (CH₂), 48.8 (CH), 36.5 (CH₃), 21.7 (CH₃), 21.5 (CH₃). MS (CI): m/z (%) = 471 (14) [MH⁺], 198 (100) [Ts(Me)NCH₂ ⁺].

14

Diethyl 2-Methyl-2-({1-[(4-methylphenyl)sulfonyl]-3-phenyl-2-aziridinyl}methyl)malonate (Table 3, Entry 3)
cis/trans-Isomers (3:1) as a colorless oil (89%); R _f = 0.30 (EtOAc-PE, 2:8). IR (film): 1761 (OCO), 1162 (SO₂) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ(cis) = 7.85 (2 H, d, J = 8.3 Hz, ArH), 7.32-7.17 (7 H, m, ArH), 4.19-4.02 (4 H, m, 2 × OCH₂), 3.87 (1 H, d, J = 7.2 Hz, NCHPh), 2.99-2.91 (1 H, m, NCHCH₂), 2.43 (3 H, s, CH₃), 1.87 (1 H, dd, J = 14.9, 5.8 Hz, CHH), 1.70 (1 H, dd, J = 14.9, 6.4 Hz, CHH), 1.31 (3 H, s, CH₃), 1.27-1.11 (6 H, m, 2 × CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 171.5 (C), 171.4 (C), 144.7 (C), 144.6 (C), 132.4 (C), 129.8 (CH), 129.6 (CH), 128.5 (CH), 128.2 (CH), 127.6 (CH), 61.8 (CH₂), 61.6 (CH₂), 52.4 (C), 45.1 (CH), 42.7 (CH), 31.1 (CH₂), 21.6 (CH₃), 19.5 (CH₃), 13.9 (CH₃), 13.8 (CH₃). ^¹H NMR (400 MHz, CDCl₃): δ(trans) = 7.78 (2 H, d, J = 8.3 Hz, ArH), 7.32-7.17 (7 H, m, ArH), 4.19-4.02 (4 H, m, 2 × OCH₂), 3.78 (1 H, d, J = 4.2 Hz, NCHPh), 2.99-2.91 (1 H, m, NCHCH₂), 2.49-2.36 (5 H, m, CH₂ and CH₃), 1.31 (3 H, s, CH₃), 1.27-1.11 (6 H, m, 2 × CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 171.5 (C), 171.4 (C), 144.4 (C), 143.6 (C), 134.8 (C), 129.8 (CH), 128.8 (CH), 128.5 (CH), 127.4 (CH), 126.7 (CH), 61.8 (CH₂), 61.7 (CH₂), 52.9 (C), 46.2 (CH), 43.7 (CH), 31.9 (CH₂), 21.6 (CH₃), 20.7 (CH₃), 13.9 (CH₃), 13.8 (CH₃). MS (CI): m/z (%) = 460 (28) [MH⁺] , 414 (17) [M⁺ - EtO], 286 (100) [M⁺ - C(CO₂Et)₂Me].

15

1-(4-Toluenesulfonyl)-2-phenyl-3-[(phenylsul-fanyl)methyl]aziridine (Table 3, Entry 6)
cis:trans-Isomers (1:5) as a colorless oil (33%); R _f = 0.45 (EtOAc-PE, 3:7). IR (film): 1347 (SO₂), 1164 (SO₂) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ(cis) = 7.58 (2 H, d, J = 8.3 Hz, ArH), 7.35-7.08 (12 H, m, ArH), 4.03 (1 H, d, J = 7.0 Hz, NCHPh), 3.29-3.19 (2 H, m, NCHCHH), 2.62 (1 H, dd, J = 14.2, 7.0 Hz, CHH), 2.36 (3 H, s, CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 143.5 (C), 137.0 (C), 135.2 (C), 134.6 (C), 129.8 (CH), 129.7 (CH), 129.1 (CH), 128.8 (CH), 128.1 (CH), 127.7 (CH), 127.1 (CH), 126.6 (CH), 46.2 (CH), 45.1 (CH), 35.4 (CH₂), 21.6 (CH₃). ^¹H NMR (400 MHz, CDCl₃): δ(trans) = 7.81 (2 H, d, J = 8.3 Hz, ArH), 7.35-7.08 (12 H, m, ArH), 4.70 (1 H, d, J = 4.2 Hz, NCHPh), 3.73 (1 H, ddd, J = 7.0, 6.5, 4.2 Hz, NCHCH₂), 3.12 (1 H, dd, J = 14.1, 6.5 Hz, CHH), 2.81 (1 H, dd, J = 14.1, 7.0 Hz, CHH), 2.42 (3 H, s, CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 144.7 (C), 137.2 (C), 135.0 (C), 134.4 (C), 129.9 (CH), 129.7 (CH), 129.6 (CH), 129.2 (CH), 129.0 (CH), 128.9 (CH), 128.2 (CH), 127.4 (CH), 48.9 (CH), 46.3 (CH), 35.6 (CH₂), 21.7 (CH₃). MS (CI): m/z (%) = 396 (3) [MH⁺], 224 (100) [MH⁺ - TsNH₂], 155 (16) [Ts⁺].

16

Diethyl 2-(Acetylamino)-2-{[3-(4-methoxyphenyl)-1-(4-toluene-sulfonyl)-2-aziridinyl]methyl}malonate (Table 4, Entry 8) cis-Isomer as a colorless oil (62%); R _f = 0.40 (EtOAc-PE, 4:6). IR (film): 1762 (OCO), 1160 (SO₂) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.79 (2 H, d, J = 8.3 Hz, ArH), 7.29 (2 H, d, J = 8.3 Hz, ArH), 7.21 (1 H, br s, NH), 6.95 (2 H, d, J = 8.7 Hz, ArH), 6.75 (2 H, d, J = 8.7 Hz, ArH), 4.41-4.09 (4 H, m, 2 × OCH₂), 3.74 (1 H, d, J = 7.2 Hz, NCHAr), 3.73 (3 H, s, OCH₃), 2.89 (1 H, ddd, J = 10.1, 7.2, 3.7 Hz, NCHCH₂), 2.53 (1 H, dd, J = 15.1, 3.7 Hz, CHH), 2.41 (3 H, s, CH₃), 2.10 (1 H, dd, J = 15.1, 10.1 Hz, CHH), 2.07 (3 H, s, CH₃), 1.33-1.15 (6 H, m, 2 × CH₃). ^¹³C NMR (100.5 MHz, CDCl₃): δ = 169.7 (C), 167.4 (C), 167.2 (C), 159.5 (C), 144.9 (C), 131.1 (C), 129.8 (CH), 128.5 (CH), 128.1 (CH), 123.8 (C), 114.0 (CH), 65.1 (C), 62.9 (CH₂), 62.7 (CH₂), 55.3 (CH₃), 45.1 (CH), 41.1 (CH), 28.9 (CH₂), 23.0 (CH₃), 21.8 (CH₃), 14.0 (CH₃), 13.9 (CH₃). MS (CI): m/z (%) = 533 (58) [MH⁺], 320 (100) [MH⁺ - TsNHAc].