New Persistent Heteroarylmethyl Radicals Resulting from the Intramolecular Addition of Aryloxymethyl Radicals onto Ketenimines. Synthesis of 2H-1,4-Benzoxazines

Abstract

A novel method for producing aryloxymethyl radicals, based on the treatment of (phenylseleno)methyl aryl ethers with tris(trimethylsilyl)silane and AIBN is disclosed, as well as the intramolecular addition of such radicals onto C,C-disubstituted ketenimines. The persistent α-(2H-1,4-benzoxazin-3-yl)benzyl radicals resulting from such cyclization processes undergo cross-coupling with the 1-cyano-1-methylethyl radical arising from the thermal ­decomposition of AIBN to give 2H-1,4-benzoxazines. These radical cyclizations are controlled by the persistent radical effect. The crystal and molecular structure of benzoxazine 10a has been solved by X-ray analysis.

Key words

ketenimine - aryloxymethyl radical - cyclization - persistent - 1,4-benzoxazines

References

• 1 Griller D. Ingold KU. Acc. Chem. Res.  1976,  9:  13 
• 2a Gomberg M. Chem. Rev.  1925,  1:  91 
• 2b Ballester M. Pure Appl. Chem.  1967,  15:  123 
• 2c Laukamp H. Nauta WT. MacLean C. Tetrahedron Lett.  1968,  9:  249 
• 2d Carilla J. Fajarí L. Juliá L. Riera J. Viadel L. Tetrahedron Lett.  1994,  35:  6529 
• 2e Neumann WP. Uzick W. Zarkadis AK. J. Am. Chem. Soc.  1986,  108:  3762 
• 2f Neumann WP. Stapel R. Chem. Ber.  1986,  119:  2006 
• 2g Sholle VD. Rozantsev EG. Russ. Chem. Rev.  1973,  42:  1011 
• 2h McBride JM. Tetrahedron  1974,  30:  2009 
• 3a Mangini A. Pedulli GF. Tiecco M. Tetrahedron Lett.  1968,  9:  4941 
• 3b Mangini A. Pedulli GF. Tiecco M. J. Heterocycl. Chem.  1969,  6:  271 
• 4 Tzerpos NI. Zarkadis AK. Kreher RP. Repas L. Lehnig M. J. Chem. Soc., Perkin Trans. 2  1995,  755 
• 5 Katritzky A. Yang B. Dalal NS. J. Org. Chem.  1998,  63:  1467 
• 6 Alajarín M. Vidal A. Tovar F. Targets Heterocycl. Syst.  2000,  4:  293 ; and references cited therein
• 7a Alajarín M. Vidal A. Ortín M.-M. Tetrahedron Lett.  2003,  44:  3027 
• 7b Alajarín M. Vidal A. Ortín M.-M. Org. Biomol. Chem.  2003,  1:  4282 
• 7c Alajarín M. Vidal A. Ortín M.-M. Bautista D. New J. Chem. in press
• For a seminal paper in which the PRE was recognized see:
• 8a Fischer H. J. Am. Chem. Soc.  1986,  108:  3925 
• 8b For the naming of the principle of PRE see: Daikh BE. Finke RG. J. Am. Chem. Soc.  1992,  114:  2938 
• 8c For an excellent review on the PRE see: Fischer H. Chem. Rev.  2001,  101:  3581 
• 8d For examples of PRE in organic synthesis see: Studer A. Angew. Chem. Int. Ed.  2000,  39:  1108 
• 8e Wetter C. Jantos K. Woithe K. Studer A. Org. Lett.  2003,  5:  2899 
• 8f Studer A. Chem.-Eur. J.  2001,  7:  1159 
• 8g Leroi C. Fenet B. Couturier J.-L. Guerret O. Ciufolini MA. Org. Lett.  2003,  5:  1079 
• 8h Allen AD. Fenwick MF. Henry-Riyad H. Tidwell TT. J. Org. Chem.  2001,  66:  5759 
• 8i Wetter C. Studer A. Chem. Commun.  2004,  174 
• 9 Boivin J. Fouquet E. Schiano A.-M. Zard SZ. Tetrahedron  1994,  50:  1769 
• 10a Walkington AJ. Whiting DA. Tetrahedron Lett.  1989,  30:  4731 
• 10b Ahmad-Junan SA. Walkington AJ. Whiting DA. J. Chem. Soc., Perkin Trans. 1  1992,  2313 
• 11 Gutenberger G. Steckhan E. Blechert S. Angew. Chem. Int. Ed.  1998,  37:  660 
• 12 Mikami T. Harada M. Narasaka K. Chem. Lett.  1999,  425 
• 13 Comasseto JV. Ferreira JTB. Brandt CA. Petragnani N. J. Chem. Res., Synop.  1982,  212 
• For examples of aza-Wittig reactions between phosphazenes and ketenes see:
• 14a

  ref. [7]

• 14b Alajarín M. Vidal A. Tovar F. Ramírez de Arellano MC. Cossío FP. Arrieta A. Lecea B. J. Org. Chem.  2000,  65:  3633 
• 14c Alajarín M. Vidal A. Ortín M.-M. Synthesis  2002,  2393 ; and references cited therein
• 15 Pracejus H. Wallura G. J. Prakt. Chem.  1962,  19:  33 
• 16 Taylor EC. McKillop A. Hawks GH. Org. Synth.  1973,  52:  36 
• For articles dealing with persistent nitrogen-centered radicals see:
• 19a Nakatsuji M. Miura Y. Teki Y. J. Chem. Soc., Perkin Trans. 2  2001,  738 
• 19b Miura Y. Momoki M. Fuchikami T. Teki Y. Itoh K. Mizutani H. J. Org. Chem.  1996,  61:  4300 
• 19c Roberts JR. Ingold KU. J. Am. Chem. Soc.  1973,  95:  3228 
• 19d Griller D. Mendenhall GD. van Hoof W. Ingold KU. J. Am. Chem. Soc.  1974,  96:  6068 

17

Typical Procedure: A solution of the corresponding ketenimine 8 (1.5 mmol) in anhyd benzene (100 mL) was heated under nitrogen at reflux temperature and tris(trimethylsilyl)silane (0.56 g, 2.25 mmol) and AIBN (0.098 g, 0.6 mmol) were added. Further additions of tris(trimethylsilyl)silane and AIBN were made as follows: 1) after 4 h since the first addition, tris(trimethylsilyl)silane (0.19 g, 0.75 mmol) and AIBN (0.098 g, 0.6 mmol) and 2) 4 h later, tris(trimethylsilyl)silane (0.37 g, 1.5 mmol) and AIBN (0.098 g, 0.6 mmol). After 16 h since the last addition the solvent was removed under reduced pressure and the crude material was chromatographed on a silica gel column, using hexanes/EtOAc (9:1) as eluent.
1,4-Benzoxazine 9f: R_f = 0.48; yield 27%; colorless prisms (Et₂O); mp 177-178 °C. IR (nujol): 2234, 1625, 1258, 1220, 1164, 1117, 1074, 1044, 964, 889, 827, 741, 707 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.23 (s, 3 H), 1.50 (s, 3 H), 3.39 (d, 1 H, J = 13.5 Hz), 4.28 (d, 1 H, J = 13.5 Hz), 6.79 (d, 1 H, J = 8.7 Hz), 7.11 (dd, 1 H, J = 8.7, 2.7 Hz), 7.41 (very broad s, 8 H), 7.61 (d, 1 H, J = 2.7 Hz), 7.91 (broad s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 25.3, 27.6, 37.3 (s), 63.6, 64.2 (s), 116.7, 127.2 (s), 127.4, 127.7 (s), 128.3, 128.5, 128.6, 128.9, 130.0, 131.1, 133.9 (s), 136.4 (s), 137.0 (s), 145.2 (s), 164.9 (s). MS: m/z (relative intensity) = 402 (3) [M⁺ + 2], 400 (8) [M⁺], 332 (100). Anal. Calcd for C₂₅H₂₁ClN₂O: C, 74.90; H, 5.28; N, 6.99. Found: C, 74.77; H, 5.21; N, 7.11.
1,4-Benzoxazine 10f: R_f = 0.36; yield 55%; colorless prisms (Et₂O); mp 143-144 °C. IR (nujol): 2233, 1624, 1600, 1579, 1494, 1299, 1261, 1236, 1198, 1128, 971, 870, 819, 763, 709, 668 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.47 (s, 3 H), 1.51 (s, 3 H), 4.77 (d, 1 H, J = 11.7 Hz), 4.92 (d, 1 H, J = 11.7 Hz), 6.82 (d, 1 H, J = 8.7 Hz), 6.99 (dd, 1 H, J = 8.7, 2.4 Hz), 7.08-7.11 (m, 2 H), 7.15 (d, 1 H, J = 2.4 Hz), 7.16-7.19 (m, 2 H), 7.28-7.35 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 27.8, 28.9, 56.8 (s), 65.2, 118.3, 121.8 (s), 123.4, 124.7, 125.1 (s), 128.1, 128.2, 128.4, 128.5, 129.8, 130.6, 132.4 (s), 139.5 (s), 140.2 (s), 142.8 (s), 147.5 (s). MS: m/z (relative intensity) = 402 (2) [M⁺ + 2], 400 (5) [M⁺], 332 (100). Anal. Calcd for C₂₅H₂₁ClN₂O: C, 74.90; H, 5.28; N, 6.99. Found: C, 74.76; H, 5.18; N, 7.08.

18

Crystallographic data for the structure 10a have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 229317. Copies of the data can be obtained on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (e-mail: [e-mail]).