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

<A NAME="RG05004ST-1">1</A> Griller D. Ingold KU. Acc. Chem. Res.  1976,  9:  13 

<A NAME="RG05004ST-2A">2a</A> Gomberg M. Chem. Rev.  1925,  1:  91 

<A NAME="RG05004ST-2B">2b</A> Ballester M. Pure Appl. Chem.  1967,  15:  123 

<A NAME="RG05004ST-2C">2c</A> Laukamp H. Nauta WT. MacLean C. Tetrahedron Lett.  1968,  9:  249 

<A NAME="RG05004ST-2D">2d</A> Carilla J. Fajarí L. Juliá L. Riera J. Viadel L. Tetrahedron Lett.  1994,  35:  6529 

<A NAME="RG05004ST-2E">2e</A> Neumann WP. Uzick W. Zarkadis AK. J. Am. Chem. Soc.  1986,  108:  3762 

<A NAME="RG05004ST-2F">2f</A> Neumann WP. Stapel R. Chem. Ber.  1986,  119:  2006 

<A NAME="RG05004ST-2G">2g</A> Sholle VD. Rozantsev EG. Russ. Chem. Rev.  1973,  42:  1011 

<A NAME="RG05004ST-2H">2h</A> McBride JM. Tetrahedron  1974,  30:  2009 

<A NAME="RG05004ST-3A">3a</A> Mangini A. Pedulli GF. Tiecco M. Tetrahedron Lett.  1968,  9:  4941 

<A NAME="RG05004ST-3B">3b</A> Mangini A. Pedulli GF. Tiecco M. J. Heterocycl. Chem.  1969,  6:  271 

<A NAME="RG05004ST-4">4</A> Tzerpos NI. Zarkadis AK. Kreher RP. Repas L. Lehnig M. J. Chem. Soc., Perkin Trans. 2  1995,  755 

<A NAME="RG05004ST-5">5</A> Katritzky A. Yang B. Dalal NS. J. Org. Chem.  1998,  63:  1467 

<A NAME="RG05004ST-6">6</A> Alajarín M. Vidal A. Tovar F. Targets Heterocycl. Syst.  2000,  4:  293 ; and references cited therein

<A NAME="RG05004ST-7A">7a</A> Alajarín M. Vidal A. Ortín M.-M. Tetrahedron Lett.  2003,  44:  3027 

<A NAME="RG05004ST-7B">7b</A> Alajarín M. Vidal A. Ortín M.-M. Org. Biomol. Chem.  2003,  1:  4282 

<A NAME="RG05004ST-7C">7c</A> 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:

<A NAME="RG05004ST-8A">8a</A> Fischer H. J. Am. Chem. Soc.  1986,  108:  3925 

<A NAME="RG05004ST-8B">8b</A> For the naming of the principle of PRE see: Daikh BE. Finke RG. J. Am. Chem. Soc.  1992,  114:  2938 

<A NAME="RG05004ST-8C">8c</A> For an excellent review on the PRE see: Fischer H. Chem. Rev.  2001,  101:  3581 

<A NAME="RG05004ST-8D">8d</A> For examples of PRE in organic synthesis see: Studer A. Angew. Chem. Int. Ed.  2000,  39:  1108 

<A NAME="RG05004ST-8E">8e</A> Wetter C. Jantos K. Woithe K. Studer A. Org. Lett.  2003,  5:  2899 

<A NAME="RG05004ST-8F">8f</A> Studer A. Chem.-Eur. J.  2001,  7:  1159 

<A NAME="RG05004ST-8G">8g</A> Leroi C. Fenet B. Couturier J.-L. Guerret O. Ciufolini MA. Org. Lett.  2003,  5:  1079 

<A NAME="RG05004ST-8H">8h</A> Allen AD. Fenwick MF. Henry-Riyad H. Tidwell TT. J. Org. Chem.  2001,  66:  5759 

<A NAME="RG05004ST-8I">8i</A> Wetter C. Studer A. Chem. Commun.  2004,  174 

<A NAME="RG05004ST-9">9</A> Boivin J. Fouquet E. Schiano A.-M. Zard SZ. Tetrahedron  1994,  50:  1769 

<A NAME="RG05004ST-10A">10a</A> Walkington AJ. Whiting DA. Tetrahedron Lett.  1989,  30:  4731 

<A NAME="RG05004ST-10B">10b</A> Ahmad-Junan SA. Walkington AJ. Whiting DA. J. Chem. Soc., Perkin Trans. 1  1992,  2313 

<A NAME="RG05004ST-11">11</A> Gutenberger G. Steckhan E. Blechert S. Angew. Chem. Int. Ed.  1998,  37:  660 

<A NAME="RG05004ST-12">12</A> Mikami T. Harada M. Narasaka K. Chem. Lett.  1999,  425 

<A NAME="RG05004ST-13">13</A> 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:

<A NAME="RG05004ST-14A">14a</A>

ref. [7]

<A NAME="RG05004ST-14B">14b</A> Alajarín M. Vidal A. Tovar F. Ramírez de Arellano MC. Cossío FP. Arrieta A. Lecea B. J. Org. Chem.  2000,  65:  3633 

<A NAME="RG05004ST-14C">14c</A> Alajarín M. Vidal A. Ortín M.-M. Synthesis  2002,  2393 ; and references cited therein

<A NAME="RG05004ST-15">15</A> Pracejus H. Wallura G. J. Prakt. Chem.  1962,  19:  33 

<A NAME="RG05004ST-16">16</A> Taylor EC. McKillop A. Hawks GH. Org. Synth.  1973,  52:  36 

<A NAME="RG05004ST-17">17</A>

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.

<A NAME="RG05004ST-18">18</A>

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:

<A NAME="RG05004ST-19A">19a</A> Nakatsuji M. Miura Y. Teki Y. J. Chem. Soc., Perkin Trans. 2  2001,  738 

<A NAME="RG05004ST-19B">19b</A> Miura Y. Momoki M. Fuchikami T. Teki Y. Itoh K. Mizutani H. J. Org. Chem.  1996,  61:  4300 

<A NAME="RG05004ST-19C">19c</A> Roberts JR. Ingold KU. J. Am. Chem. Soc.  1973,  95:  3228 

<A NAME="RG05004ST-19D">19d</A> Griller D. Mendenhall GD. van Hoof W. Ingold KU. J. Am. Chem. Soc.  1974,  96:  6068