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.

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 

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]).

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