Intermolecular Alkyl Radical Addition to Methyl 2-(2,6-Dichlorophenyl)-2H-azirine-3-carboxylate

Abstract

The 2H-azirine 1 acts as an effective radical acceptor for secondary and tertiary alkyl iodides mediated by triethylborane. The addition proceeds with high regio- and diastereo-selectivity.

Key words - 2H-azirine - intermolecular radical addition - triethyl­borane

References

For reviews see:

1a Friestad GK. Tetrahedron  2001,  57:  5461 

1b Naito T. Heterocycles  1999,  50:  505 

1c Fallis AG. Brinza IM. Tetrahedron  1997,  53:  17543 

For some examples see:

2a Miyabe H. Ueda M. Nishimura A. Naito T. Org. Lett.  2002,  4:  131 

2b Kim S. Kavali R. Tetrahedron Lett.  2002,  43:  7189 

2c Halland N. Jorgensen KA. J. Chem. Soc., Perkin Trans. 1  2001,  1290 

2d Miyabe H. Ueda M. Naito T. J. Org. Chem.  2000,  65:  5043 

2e Bertrand MP. Stephanie C. Feray L. Nouguier R. Perfetti P. Tetrahedron  2000,  56:  3951 

2f Miyabe H. Ueda M. Yoshioka N. Yamakawa K. Naito T. Tetrahedron  2000,  56:  2413 

2g Miyabe H. Fujishima Y. Naito T. J. Org. Chem.  1999,  64:  2174 

2h Bertrand MP. Feray L. Nouguier R. Perfetti P. J. Org. Chem.  1999,  64:  9189 

2i Miyabe H. Ueda M. Yoshioka N. Naito T. Synlett  1999,  465 

2j Miyabe H. Yamakawa K. Yoshioka N. Naito T. Tetrahedron  1999,  55:  11209 

2k Miyabe H. Shibata R. Sangawa M. Ushiro C. Naito T. Tetrahedron  1998,  54:  11431 

2l Miyabe H. Shibata R. Ushiro C. Naito T. Tetrahedron Lett.  1998,  39:  631 

2m Miyabe H. Ushiro C. Naito T. Chem. Commun.  1997,  1789 

3a Miyabe H. Fujii K. Naito T. Org. Biomol. Chem.  2003,  1:  381 

3b Friestad GK. Qin J. J. Am. Chem. Soc.  2001,  123:  9922 

3c Friestad GK. Qin J. J. Am. Chem. Soc.  2000,  122:  8329 

3d Bertrand MP. Feray L. Nouguier R. Perfetti P. Synlett  1999,  1148 

3e Miyabe H. Fujii K. Naito T. Org. Lett.  1999,  1:  569 

3f Bertrand MP. Feray L. Nouguier R. Stella L. Synlett  1998,  780 

4a Gilchrist TL. Aldrichimica Acta  2001,  34:  51 

4b Alves MJ. Azoia NG. Bickley JF. Fortes AG. Gilchrist TL. Mendonca R. J. Chem. Soc., Perkin Trans. 1  2001,  2969 

4c Alves MJ. Gilchrist TL. Sousa JH. J. Chem. Soc., Perkin Trans. 1  1999,  1305 

5 Review: Ollivier C. Renaud P. Chem. Rev.  2001,  101:  3415 

6

CCDC 207633 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax:[phone]; e-mail: [e-mail].).

7 Yamada K. Fujihara H. Yamamoto Y. Miwa Y. Taga T. Tomioka K. Org. Lett.  2002,  4:  3509 

8

Typical Procedure: A solution of triethylborane (15% in hexane) (0.4 mL, 6.12 mmol) was added to a mixture of methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxylate (0.3g, 1.23 mmol) and the alkyl iodide (12.4 mmol) in CH₂Cl₂ (20 mL) at -40 °C. The reaction was maintained at this temperature for 30 min and the mixture was then washed with a 10% aq solution of NaHCO₃ the organic layer dried (Na₂SO₄) and evaporated. Flash chromatography (hexanes/EtOAc: 80/20) afforded the product.
With iodoethane: Methyl 3-(2,6-dichlorophenyl)-2-ethylaziridine-2-carboxylate 2a, 0.24 g (71%), mp 53.0-54.5 °C (from toluene/CH₂Cl₂). (Found: C, 52.28; H, 4,92; N, 5,07. C₁₂H₁₃Cl₂NO₂ requires C, 52.57; H, 4.78; N, 5.11%). IR ν_max = 1724, 1433, 1207, 777 cm^-1. ¹H NMR (300 ΜΗz): δ = 1.11 (3 H, t, J = 7.5 Hz), 1.52-1.64 (1 H, m, CH₃HCH), 2.41-2.53 (2 H, m, CH₃HCH and NH, integration became one after D₂O shake), 3.12 (1 H, br s, H-3, turns into a sharp singlet after D₂O shake), 3.57 (3 H, s,) 7.12-7.17 (1 H, m), 7.27-7.29 (2 H, m). MS (CI): m/z (%) = 274 (100), 276 (66), 278 (12) [(M + H)⁺].
With 2-iodopropane: Methyl 3-(2,6-dichlorophenyl)-2-(1-methylethyl) aziridine-2-carboxylate 2b, 0.29 g (82%); mp 81.7-82.9 (from hexanes/EtOAc). (Found: C, 53.96; H, 5.47; N, 5.03; C₁₃H₁₅Cl₂NO₂ requires C, 54.18; H, 5.25; N, 4.86%). IR ν_max = 3209, 2968, 1724, 1433, 1207, 775 cm^-1. ¹H NMR (300 Μz): δ = 1.2 (9 H, s), 2.66 (1 H, br d, J = 7.3 Hz, aziridine NH), 3.28 (1 H, br d, J = 7.1 Hz, H-3), 3.47 (3 H, s) 7.10-7.16 (1 H, m), 7.25-7.28 (2 H, m). MS (CI): m/z (%) = 288 (100), 290 (66), 292 (12) [(M + H)⁺].
With 2-iodo-2-methylpropane: Methyl 3-(2,6-dichloro-phenyl)-2-(1,1-dimethylethyl)aziridine-2-carboxy-late 2c (0.33 g, 89%), as a low melting point solid. IR ν_max = 3406, 2959, 1714, 1431, 1242, 774 cm^-1. ¹H NMR (300 Μz): δ = 1.2 (9 H, s), 2.66 (1 H, bd, J = 7.3 Hz, aziridine NH), 3.28 (1 H, bd, J = 7.1 Hz, H-3), 3.47 (3 H, s) 7.10-7.16 (1 H, m), 7.25-7.28 (2 H, m).
With iodocyclohexane: Methyl 3-(2,6-dichlorophenyl)-2-cyclohexylaziridine-2-carboxylate 2d, (0.32 g, 79%), mp 105.6-107.2 °C (from toluene/CH₂Cl₂), IR ν_max = 3209, 2967, 1724, 1433, 1207, 775 cm^-1. ¹H NMR (300 Μz): δ = 1.08-1.9 (10 H, multiplet), 2.29 (1 H, br t, J = 4.2 Hz), 2.54 (1 H, br s, NH), 3.28 (1 H, br s), 7.10-7.16 (1 H, m), 7.26-7.29 (2 H, m).

9 Giese B. In Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds   Pergamon Press; Oxford: 1986. 

10

Similar mechanisms, for borane mediated reactions, have been proposed, see references: 1a) p. 5488; 2c); 2i); 2j); 5) p. 3429; 9) p. 86.