radicals are the key intermediates in many azide cyclization/
rearrangement processes mediated by tributyltin hydride
(Bu3SnH) and AIBN.1,4
Iminyl Radicals from r-Azido o-Iodoanilides via
1,5-H Transfer Reactions of Aryl Radicals: New
Transformation of r-Azido Acids to
Decarboxylated Nitriles
The radical chemistry of azides has invariably been confined
to the generation and synthetic applications of aminyl radicals,
although a work appeared in 1997 seemingly suggesting that
alkyl azides might additionally act as progenitors of iminyl
radicals, provided that transient radicals be produced on the
carbon atom linked to the azido function.5 The radical chain
reaction of benzenethiol with R-azidostyrenes was found to
afford virtually quantitative yields of ꢀ-sulfanylated imines and
tautomeric enamines clearly ascribable to the intervention of
2-sulfanyliminyl radicals. These intermediates could result from
sulfanyl radical attack at the azide ꢀ-carbon followed by
ꢀ-elimination of molecular nitrogen from the ensuing R-azido-
benzyl radical adduct.5 Surprisingly, despite that promising
chemical information, the potential utility of alkyl azides in the
production of iminyl radicals has remained to date totally
ignored.
Giorgio Bencivenni, Tommaso Lanza, Rino Leardini,*
Matteo Minozzi, Daniele Nanni, Piero Spagnolo,* and
Giuseppe Zanardi
Dipartimento di Chimica Organica “A. Mangini”, UniVersita`
di Bologna, Viale Risorgimento 4, I-40136 Bologna, Italy
ReceiVed February 26, 2008
Iminyl radicals are of significant interest in synthetic radical
chemistry due to their ability to perform cyclizations onto
aromatic rings6a,e,f and double bonds, 7 and additional fragmen-
tation reactions to give nitrile products.5,7b,8 These nitrogen
species have been formerly generated by various methods, i.e.,
thermolysis, photolysis, or flash vacuum pyrolysis of N-
substituted imine derivatives,6a–d intramolecular addition of
carbon6e,f,8b,c and nitrogen radicals4g to nitriles, and radical-
chain reactions of Bu3SnH with sulfanylimines,9a benzotriazo-
lylimines,8a and xanthic hydrazones.9b,c
The radical reaction of tributyltin hydride with o-iodo-N-
methylanilides derived from R-azido acids provides an
excellent access to R-(aminocarbonyl)iminyl radicals through
1,5-hydrogen transfer reaction of initially formed aryl radicals
followed by ꢀ-elimination of dinitrogen from ensuing
R-azido-R-(aminocarbonyl)alkyl radicals. The outcoming
iminyls display a peculiar tendency to form corresponding
nitriles by ꢀ-elimination of aminocarbonyl radicals.
(3) (a) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem. 2006, 71, 5822. (b) Benati,
L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo,
P.; Zanardi, G. J. Org. Chem. 2006, 71, 434. (c) Benati, L.; Bencivenni, G.;
Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo, P.; Strazzari, S.;
Zanardi, G.; Rizzoli, C. Org. Lett. 2006, 8, 2499.
In recent years considerable attention has been devoted to
the radical chemistry of alkyl and aryl azides, which have
been shown to act, to a varying degree, as radical acceptors
toward a range of carbon- and heteroatom-centered species
yielding aminyl radicals after nitrogen loss from initial
triazenyl adducts.1 The intramolecular additions of carbon
radicals usefully afford cyclic aminyl radicals that are
valuable intermediates for the synthesis of N-heterocycles.2
The intermolecular additions of silyl,3a germyl,3b indyl,3c and,
mainly, stannyl radicals1 efficiently lead to corresponding
N-substituted aminyl radicals. In particular, N-stannylaminyl
(4) Selected examples:(a) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc.
1993, 115, 3328. (b) Kim, S.; Kim, S. S.; Seo, H. S.; Yoon, K. S. Tetrahedron
1995, 51, 8437. (c) Kim, S.; Do, J. Y. Chem. Commun. 1995, 1607. (d)
Hornemann, A. M.; Lundt, I. J. Org. Chem. 1998, 63, 1919. (e) Hays, D. S.; Fu,
G. C. J. Org. Chem. 1998, 63, 2796. (f) Moreno-Vargas, A. J.; Vogel, P.
Tetrahedron Lett. 2003, 44, 5069. (g) Benati, L.; Bencivenni, G.; Leardini, R.;
Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo, P.; Strazzari, S.; Zanardi, G.;
Rizzoli, C. Org. Lett. 2004, 6, 417.
(5) Montevecchi, P. C.; Navacchia, M. L.; Spagnolo, P. J. Org. Chem. 1997,
62, 5846.
(6) (a) Atmaran, S.; Forrester, A. E.; Gill, M.; Thomson, R. H. J. Chem.
Soc., Perkin Trans. 1 1981, 1721. (b) Black, M.; Cadogan, J. I. M.; Leardini,
R.; McDougald, G.; McNab, H.; Nanni, D.; Reed, D.; Zompatori, A. J. Chem.
Soc., Perkin Trans. 1 1988, 1825. (c) Leardini, R.; McNab, H.; Nanni, D.;
Parsons, S.; Reed, D.; Tenan, A. G. J. Chem. Soc., Perkin Trans. 1 1998, 1833.
(d) Creed, T.; Leardini, R.; McNab, H.; Nanni, D.; Nicolson, I. S.; Reed, D.
J. Chem. Soc., Perkin Trans. 1 2001, 1079. (e) Bowman, W. R.; Bridge, C. F.;
Cloonan, M. O.; Leach, D. C. Synlett 2001, 765. (f) Bowman, W. R.; Bridge,
C. F.; Brookes, P.; Cloonan, M. O.; Leach, D. C. J. Chem. Soc., Perkin Trans.
1 2002, 58.
(1) (a) Roberts, B. P.; Dang, H.-S. J. Chem. Soc., Perkin Trans. 1 1996,
1493. (b) Benati, L.; Nanni, D.; Sangiorgi, C.; Spagnolo, P. J. Org. Chem. 1999,
64, 7836. (c) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.;
Strazzari, S.; Zanardi, G.; Calestani, G. Tetrahedron 2002, 58, 3485. (d) Benati,
L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo,
P.; Zanardi, G. J. Org. Chem. 2005, 70, 3046.
(7) For reviews on aminyl radical cyclizations onto alkenes, see:(a) Zard,
S. Z. Synlett 1996, 1148. (b) Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53,
17543.
(2) Selected examples:(a) Benati, L.; Montevecchi, P. C.; Spagnolo, P.
Tetrahedron Lett. 1978, 815. (b) Benati, L.; Montevecchi, P. C. J. Org. Chem.
1981, 46, 4570. (c) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc. 1994, 116,
5521. (d) Montevecchi, P. C.; Navacchia, M. L.; Spagnolo, P. Eur. J. Org. Chem.
1998, 1219. (e) Kizil, M.; Patro, B.; Callaghan, O.; Murphy, J. A.; Hursthouse,
M. B.; Hibbs, D. J. Org. Chem. 1999, 64, 7856. (f) Benati, L.; Leardini, R.;
Minozzi, M.; Nanni, D.; Spagnolo, P.; Strazzari, S.; Zanardi, G. Org. Lett. 2002,
4, 3079. (g) Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
Spagnolo, P.; Strazzari, S. Org. Lett. 2003, 5, 1313.
(8) (a) Kaim, L. E.; Meyer, C. J. Org. Chem. 1996, 61, 1556. (b) Bowman,
W. R.; Bridge, C. F.; Brookes, P. Tetrahedron Lett. 2000, 41, 8989. (c) Crich,
D.; Bowers, A. A. J. Org. Chem. 2006, 71, 3452.
(9) (a) Boivin, J.; Fouquet, E.; Zard, S. Z. Tetrahedron 1994, 50, 1745. (b)
LeTadic-Biadatti, M. H.; Callier-Doublanchet, A.-C.; Horner, J. H.; Quiclet-
Sire, B.; Zard, S. Z.; Newcomb, M. J. Org. Chem. 1997, 62, 559. (c) Callier-
Doublanchet, A.-C.; Horner, J. H.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron
Lett. 1995, 36, 8791.
10.1021/jo800453z CCC: $40.75
Published on Web 05/10/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 4721–4724 4721