Radical Reduction of Aromatic Azides to Amines
with Tributylgermanium Hydride
mediated by Bu3SnH/AIBN; these include, inter alia, reductions
4d,5
of azides to amines, conversions of cyclic azidoalkyl ketones
4
a,b,d,6
to medium-sized lactams,
rearrangements of alkyl azides
7
to alkylideneanilines, ring expansions of azidoazabicyclo[2.2.1]-
heptanes to diazabicyclo[3.2.1]octanes, and additionally, tandem
Luisa Benati, Giorgio Bencivenni, Rino Leardini,*
Matteo Minozzi, Daniele Nanni, Rosanna Scialpi,
Piero Spagnolo,* and Giuseppe Zanardi
8
cyclizations of azidoalkylmalononitriles leading to pyrrolopyr-
9
roles and pyrrolopyridines. Despite the fact that the reaction
Dipartimento di Chimica Organica “A. Mangini”,
UniVersit a` di Bologna, Viale Risorgimento 4,
I-40136 Bologna, Italy
of azides with Bu3SnH/AIBN provides a most convenient entry
to valuable aminyl radicals, this method is unfortunately limited
by the known toxicity of Bu3SnH and other organotin hydrides
and, additionally, the serious problems connected with full
removal of tin residues from reaction mixtures. Therefore, the
alternative use of other nontoxic group XIV hydrides such as
the organosilicon or organogermanium ones is a crucial goal
for synthetic applications of those nitrogen intermediates.
ReceiVed October 18, 2005
1
0
However, although as early as 1979 triorganosilyl radicals
derived from silanes were reported to react with a variety of
azides and display EPR spectra ascribable to silyltriazenyl
adducts, the synthetic potential of these radical reactions has
2
d
since remained virtually unexplored. As far as triorganoger-
manium hydrides, to our knowledge their reactivity toward
azides is to date totally unknown.
Aromatic azides are inert toward tributylgermanium hydride
under thermal conditions in the absence and in the presence
of a radical initiator but in the presence of catalytic amounts
of benzenethiol undergo fast reaction, yielding reduced
anilines and 2-germylated derivatives in high overall yields.
Our long interest in the radical chemistry of azides prompted
us to undertake a study of the radical reaction of tributylger-
manium hydride (Bu3GeH) with aryl azides with the hope of
producing N-germylaminyl radical intermediates (and thence
reduced amines). The choice of Bu3GeH was suggested by a
Organic azides are important intermediates that have found
extensive use in the synthesis of acyclic and cyclic nitrogen-
containing compounds. The utility of these versatile intermedi-
ates comes from their fair ability to react with electrophilic and
nucleophilic species, additionally acting as 1,3-dipoles in
cycloaddition reactions as well as affording reactive nitrenes
1
1
very recent work of Bowman and co-workers, which showed
1
2
that this hydride can be used as a promising alternative to
Bu3SnH with a wide range of radical substrates.
Preliminary experiments established that Bu3GeH, contrary
13
to the tin counterpart, was totally inert toward various electron-
1
under thermal and photochemical conditions. Radical reactions
(
5) (a) Frankel, M.; Wagner, D.; Gertner, D.; Zikha, A. J. Organomet.
Chem. 1967, 7, 518. (b) Samano, M. C.; Robins, M. J. Tetrahedron Lett.
991, 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,
3, 1919. (e) Hays, D. S.; Fu, G. C. J. Org. Chem. 1998, 63, 2796. (f)
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 In particular, the thermal reactions
with tributyltin hydride (Bu3SnH), in the presence of a radical
initiator (AIBN), smoothly afford N-stannylaminyl radicals
through loss of nitrogen by intermediate 1,3- and/or 3,3-
1
,3
6
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,
4
stannyltriazenyl radical adducts. The stannylaminyl radicals
1
01, 192378c.
actually occur as key intermediates in numerous azide processes
(6) Benati, L.; Nanni, D.; Sangiorgi, C.; Spagnolo, P. J. Org. Chem.
1
999, 64, 7836.
(
1) (a) The Chemistry of the Azido Group; Patai, S., Ed.; Wiley: New
(7) Kim, S.; Do, J. Y. J. Chem. Soc., Chem. Commun. 1995, 1607.
(8) Moreno-Vargas, A. J.; Vogel, P. Tetrahedron Lett. 2003, 44, 5069.
(9) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
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.
Scialpi, R.; Spagnolo, P.; Strazzari, S.; Zanardi, G.; Rizzoli, C. Org. Lett.
2004, 6, 417.
(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,
(10) (a) Roberts, B. P.; Winter, J. N. J. Chem. Soc., Perkin Trans. 2
1979, 1353. (b) Brand, J. C.; Roberts, B. P.; Winter, J. N. J. Chem. Soc.,
Perkin Trans. 2 1983, 261.
4
6, 4570. (c) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc. 1994, 116,
5
521. (d) Montevecchi, P. C.; Navacchia, M. L.; Spagnolo, P. Eur. J. Org.
(11) Bowman, W. R.; Krintel, S. L.; Schilling, M. B. Org. Biomol. Chem.
2004, 2, 585.
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.
(12) Tributylgermanium hydride can be purchased from Aldrich or Acros,
but the commercial compound, especially that from Aldrich, is expensive.
However, the hydride can be easily prepared in the laboratory on a large
scale through a Cp2TiCl2-catalyzed Grignard reaction between germanium
tetrachloride and butylmagnesium chloride for ca. five times the price of
the purchase of Bu3SnH. Part of this excess cost is offset by the superior
stability and the lack of wastage commonly encountered with the use of
Bu3SnH, see: Colacot, T. J. J. Organomet. Chem. 1999, 580, 378 and ref
11.
(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,
6
9, 2755.
(4) (a) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc. 1993, 115,
3
5
1
328. (b) Kim, S.; Kim, S. S.; Seo, H. S.; Yoon, K. S. Tetrahedron 1995,
1, 8437. (c) Dang, H.-S.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 1
996, 1493. (d) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni,
(13) In the absence of a radical initiator, Bu3SnH normally converts azides
to amines through thermally unstable stannyltriazene adducts; see ref 4d
and references therein.
D.; Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem. 2005, 70, 3046.
10.1021/jo0521697 CCC: $33.50 © 2006 American Chemical Society
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J. Org. Chem. 2006, 71, 434-437
Published on Web 11/22/2005