due to the recent finding that aryl azides can be generally
produced in very good yields upon CuI-catalyzed coupling
reaction of the corresponding iodides and bromides with sodium
azide under mild thermal conditions.6
Radical Reduction of Aromatic Azides to Amines
with Triethylsilane
Luisa Benati, Giorgio Bencivenni, Rino Leardini,
Matteo Minozzi,* Daniele Nanni,* Rosanna Scialpi,
Piero Spagnolo,* and Giuseppe Zanardi
The conversion of azides to amines can be achieved by a
large variety of reported methods.1,7 The procedure involving
tributyltin hydride (Bu3SnH) in the presence of a radical initiator
(AIBN) has found almost invariable use to perform that process
under radical conditions.8,9 Incidentally, the N-stannylaminyl
radicals involved in this process can alternatively act as key
intermediates in numerous interesting azide cyclization/re-
arrangement processes mediated by Bu3SnH/AIBN.8,10 This
method is unfortunately limited by the known toxicity of
organotin compounds and, additionally, the serious problems
connected with full removal of tin residues from the reaction
mixtures. Therefore, replacement of Bu3SnH with other nontoxic
group XIV hydrides, such as the organosilicon or organoger-
manium ones, is highly desirable. On this basis, in a very recent
work, we have made first successful use of a triorganogerma-
nium hydride (Bu3GeH) in the radical aryl azides reduction.11
To circumvent the poor hydrogen-donating properties of the
germanium hydride, the procedure has been carried out follow-
ing the “polarity reversal catalysis” technique introduced by
Roberts12 and upgraded by Bowman,13 that is, by using Bu3-
GeH in the presence of catalytic benzenethiol in refluxing
toluene (Scheme 1, Y ) Ph, X ) Bu3Ge).14 Our tin-free radical
Dipartimento di Chimica Organica “A. Mangini”, UniVersita` di
Bologna, Viale Risorgimento 4, I-40136 Bologna, Italy
ReceiVed April 19, 2006
Aromatic azides are inert toward triethylsilane under thermal
conditions in the presence of a radical initiator, but in the
presence of additional catalytic amounts of tert-do-
decanethiol, they afford anilinosilanes and thence the cor-
responding anilines in virtually quantitative yields.
Since the discovery of organic azides more than a century
ago, numerous syntheses of these energy-rich molecules have
been exploited and their applications in organic synthesis have
enormously widened.1 Radical reactions of azides are still less
documented, but the reported studies have clearly revealed that
these reactions also provide useful synthetic routes to N-
heterocycles.2,3
Straightforward reduction to amines is one of the most
attractive synthetic applications of azides. Since aliphatic azides
are readily available from the corresponding halides and
sulfonates, they serve as one of the most reliable ways to
introduce an amino substituent onto an aliphatic carbon. The
conversion of aromatic azides into anilines has received
relatively modest interest until very recently, especially since
those azides have been mostly produced from the anilines
themselves via their diazonium salts.1,4,5 Nowadays, an easy
entry to anilines from aryl azides has become highly appealing
(5) Rodriguez, J. A. R.; Abramovitch, R. A.; de Souse, J. D. F.; Leiva,
G. C. J. Org. Chem. 2004, 69, 2920.
(6) (a) Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6,
2571. (b) Zhu, W.; Ma, D. Chem. Commun. 2004, 888. (c) Cai, Q.; Zhu,
W.; Zhang, Y.; Ma, D. Synthesis 2005, 498. (d) Andersen, J.; Madsen, U.;
Bjorkling, F.; Liang, X. Synlett 2005, 2209. (e) Andersen, J.; Bolvig, S.;
Liang, X. Synlett 2005, 2941.
(7) For a comprehensive review on azide reduction methods, see:
Amantini, D.; Fringuelli, F.; Pizzo, F.; Vaccaro, L. Org. Prep. Proc. Int.
2002, 34, 109.
(8) (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) Dang, H.-S.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 1
1996, 1493. (d) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni,
D.; Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem. 2005, 70, 3046.
(9) (a) Frankel, M.; Wagner, D.; Gertner, D.; Zikha, A. J. Organomet.
Chem. 1967, 7, 518. (b) Samano, M. C.; Robins, M. J. Tetrahedron Lett.
1991, 32, 6293. (c) Poopeiko, N. E.; Pricota, T. I.; Mikhailopulo, I. A.
Synlett 1991, 342. (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)
Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.; Strazzari,
S.; Zanardi, G. Tetrahedron 2002, 58, 3485. (g) Zaitseva, V. E.; Dyatkina,
N. B.; Kraevskii, A. A.; Skaptsova, N. V.; Turina, O. V.; Gottikh, B. P.;
Azhaev, A. V. Bioorg. Khim. (Moscow) 1984, 10, 670; Chem. Abstr. 1984,
101, 192378c.
(10) (a) Benati, L.; Nanni, D.; Sangiorgi, C.; Spagnolo, P. J. Org. Chem.
1999, 64, 7836. (b) Kim, S.; Do, J. Y. Chem. Commun. 1995, 1607. (c)
Moreno-Vargas, A. J.; Vogel, P. Tetrahedron Lett. 2003, 44, 5069. (d)
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.
(11) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem. 2006, 71, 434. Also a
group XIII hydride, namely, dichloroindium hydride, has just been proved
to react smoothly with organic azides: Benati, L.; Bencivenni, G.; Leardini,
R.; Nanni, D.; Minozzi, M.; Spagnolo, P.; Scialpi, R.; Zanardi, G. Org.
Lett. 2006, 8, 2499.
(12) (a) Roberts, B. P. Chem. Soc. ReV. 1999, 28, 25. (b) Dang, H.-S.;
Roberts, B. P.; Tocher, D. A. J. Chem. Soc., Perkin Trans. 1 2001, 2452.
(c) Cai, Y.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 2 2002, 1858.
(13) Bowman, W. R.; Krintel, S. L.; Schilling, M. B. Org. Biomol. Chem.
2004, 2, 585.
(1) (a) The Chemistry of the Azido Group; Patai, S., Ed.; Wiley: New
York, 1971. (b) Azides and Nitrenes: ReactiVity and Utility; Scriven, E. F.
V., Ed.; Academic Press: New York, 1984. (c) Scriven, E. F. V.; Turnbull,
R. Chem. ReV. 1988, 88, 297. (d) Bra¨se, S.; Gil, C.; Knepper, K.;
Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44, 5188.
(2) For selected reactions of carbon-centered radicals with alkyl and aryl
azides, see: (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) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.;
Spagnolo, P.; Strazzari, S.; Zanardi, G. Org. Lett. 2002, 4, 3079. (f) Lizos,
D. E.; Murphy, J. A. Org. Biomol. Chem. 2003, 1, 117.
(3) For recent examples of radical azidations using sulfonyl azides, see:
(a) Renaud, P.; Ollivier, C. J. Am. Chem. Soc. 2001, 123, 4717. (b) Renaud,
P.; Ollivier, C.; Panchaud, P. Angew. Chem., Int. Ed. 2002, 41, 3460. (c)
Renaud, P.; Ollivier, C.; Panchaud, P.; Zigmantas, S. J. Org. Chem. 2004,
69, 2755.
(4) Liu, Q.; Tor, Y. Org. Lett. 2003, 5, 2571 and references cited therein.
10.1021/jo060824k CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/24/2006
5822
J. Org. Chem. 2006, 71, 5822-5825