ORGANIC
LETTERS
2012
Vol. 14, No. 17
4610–4613
A Protocol for Accessing the β‑Azidation
of r,β-Unsaturated Carboxylic Acids
Tommaso Angelini,† Simona Bonollo,† Daniela Lanari,†,‡ Ferdinando Pizzo,† and
Luigi Vaccaro*,†
Laboratory of Green Synthetic Organic Chemistry, CEMIN - Dipartimento di Chimica,
ꢀ
Universita di Perugia, Via Elce di Sotto, 8, Perugia, Italy, and Dipartimento di Chimica e
Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 06123, Perugia, Italy
ꢀ
Received July 26, 2012
ABSTRACT
This contribution reports the preparation and use of a new immobilized catalyst, PS-DABCOF (9), which has been specifically designed to access
for the first time the efficient β-azidation of r,β-unsaturated carboxylic acids.
The researchon β-amino acids and β-peptideshasgrown
dramatically in the past 15 years, since these compounds
are endowed with a wide range of biological activities and
pharmacological properties.1
There are different approaches for the synthesis of
β-amino acids, including R-amino acid homologation,2
addition of enolates or enolate equivalents to imines,3
conjugate addition to electron-deficient olefins,4 and nucleo-
philic ring-opening reaction of β-lactones.5 Among these
methods, aza-Michael addition is one of the most attrac-
tive and several procedures have been reported where
amines6 or N-nucleophiles7 react with R,β-unsaturated
carbonyl compounds. In particular, Michael addition of
the azido ion is an attractive procedure to prepare β-amino
acids, since azides can be easily converted into the corre-
sponding amines. Moreover, β-peptides can be directly built
with the so-called “azido acid approach”,8 exploiting the
azido group as an N-protecting group for a β-amino acid.
Efficient methods for the Lewis acid or Lewis base
catalyzed Michael addition of azides to R,β-unsaturated
carbonyl compounds including unsaturated imides are
known,9 but there are no procedures for the azidation of
R,β-unsaturated carboxylic acids.
The efficient Miller’s procedure is based on the use of a
tertiary amine as the catalyst which is responsible for the
controlled production of hydrazoic acid (the effective azida-
tion reagent) from a 1:1 mixture of TMSN3 and AcOH.9f
We have reported the use of polystyrene-supported
ammonium fluoride (Amberlite IRA900F, Amb-F, and
† CEMIN - Dipartimento di Chimica.
‡ Dipartimento di Chimica e Tecnologia del Farmaco.
(1) (a) Seebach, D.; Beck, A. K.; Capone, S.; Deniau, G.; Groselj, U.;
ꢁ
Zass, E. Synthesis 2009, 1–32. (b) Liu, M.; Sibi, M. P. Tetrahedron 2002,
58, 7991–8035.
(2) (a) Byrne, C. M.; Church, T. L.; Kramer, J. W.; Coates, G. W.
€
Angew. Chem., Int. Ed. 2008, 47, 3979–3983. (b) Flogel, O.; Casi, G.;
Hilvert, D.; Seebach, D. Helv. Chim. Acta 2007, 90, 1651–1666. (c) Gray,
D.; Concellc-on, C.; Gallagher, T. J. Org. Chem. 2004, 69, 4849–4851.
ꢀ
(3) Arrayas, R. G.; Carretero, J. C. Chem. Soc. Rev. 2009, 38,
1940–1948.
(4) Enders, D.; Wang, C.; Liebich, J. X. Chem.;Eur. J. 2009, 15,
11058–11076.
(5) (a) Armstrong, A.; Geldart, S. P.; Jenner, C. R.; Scutt, J. N.
J. Org. Chem.2007, 72, 8091–8094. (b) Nelson, S. G.; Spencer, K. L.;
Cheung, W. S.; Mamie, S. J. Tetrahedron 2002, 58, 7081–7091. (c) Nelson,
S. G.; Spencer, K. L. Angew. Chem., Int. Ed. 2000, 39, 1323–1325.
(8) Wang, X.; Nelson, S. G.; Curran, D. P. Tetrahedreon 2007, 63,
6141–6145.
(9) (a) Taylor, M. S.; Zalatan, D. N.; Lerchner, A. M.; Jacobsen,
E. N. J. Am. Chem. Soc. 2005, 127, 1313–1317. (b) Xu, L.-W.; Li, L.; Xia,
C.-G.; Zhou, S. L.; Li, J. W. Tetrahedron Lett. 2004, 45, 1219–1221.
(c) Guerin, D. J.; Miller, S. J. J. Am. Chem. Soc. 2002, 124, 2134–2136.
(d) Horstmann, T. E.; Guerin, D. J.; Miller, S. J. Angew. Chem., Int. Ed.
2000, 39, 3635–3638. (e) Mayers, J. K.; Jacobsen, E. N. J. Am. Chem.
Soc. 1999, 121, 8959–8960. (f) Guerin, D. J.; Horstmann, T. E.; Miller,
S. J. Org. Lett. 1999, 1, 1107–1109.
€
(6) (a) Weiss, M.; Groger, H. Synlett 2009, 1251–1254. (b) Node, M.;
Hashimoto, D.; Katoh, T.; Ochi, S.; Ozeki, M.; Watanabe, T.; Kajimoto, T.
Org. Lett. 2008, 10, 2653–2656.
(7) (a) Chen, L.-Y.;He, H.;Pei, B. J.;Chan, W.-H.;Lee, A. W.Synthesis
2009, 1573–1577. (b) Vesely, J.; Ibrahem, I.; Rios, R.; Zhao, G.-L.; Xu, Y.;
ꢀ
Cordova, A. Tetrahedron Lett. 2007, 48, 2193–2198. (c) Wabnitz, T. C.; Yu,
J.-Q.; Spencer, J. B. Chem.;Eur. J. 2004, 10, 484–493.
r
10.1021/ol302069h
Published on Web 08/14/2012
2012 American Chemical Society