S. Gil et al. / Tetrahedron Letters 48 (2007) 3451–3453
3453
CN
Field, M. J.; Vartanian, M. G.; Kinsora, J. J.; Lotarski, S.
M.; El-Kattan, A.; Walters, K.; Cherukury, M.; Taylor, C.
P.; Wustrow, D. J.; Schwarz, J. B. Bioorg. Med. Chem.
Lett. 2006, 16, 2333; (b) Denis, J.-N.; Tchertchian, S.;
Tomassini, A.; Vall e´ e, Y. Tetrahedron Lett. 1997, 38, 5503;
57%
S
COOH
S
COOH
COOH
9
1) Et2NLi
1
0
(
c) Azam, S.; D’Souza, A. A.; Wyatt, P. B. J. Chem. Soc.,
COOH
2) BrCH2CN
Perkin Trans. 1 1996, 621.
6
7
. See for example: (a) Martin, C. J.; Rawson, D. J.;
Williams, J. M. J. Tetrahedron: Asymmetry 1998, 9,
3723; (b) Dryonska, V.; Pasnkuleva, I. Org. Prep. Proced.
Int. 1999, 31, 232.
. (a) Calm e` s, M.; Escale, F.; Martinez, J. Tetrahedron:
Asymmetry 2002, 13, 293; (b) Camps, P.; Mu n˜ oz-Torrero,
D.; S a´ nchez, L. Tetrahedron: Asymmetry 2004, 15, 311.
7
0%
O
CN
O
12
11
Scheme 3. Reaction of bromoacetonitrile with o-methyl aromatic
acids.
of a, and c adducts were observed. It is worth noting
that the regioselectivity is modified according to the pro-
gress of the reaction. This phenomenon is explained by
8. (a) Thomson, C. M. Dianion Chemistry in Organic
Synthesis; CRC Press: Boca Raton (FL), 1994; pp 88–
1
29; (b) Gil, S.; Parra, M. Curr. Org. Chem. 2002, 6, 283;
(
c) Gil, S.; Parra, M. Recent Res. Dev. Org. Chem. 2002, 6,
the presence of LiBr; generated as the reaction pro-
gresses (Scheme 2).17
449.
9
. Clayden, I. Organolithiums: Selectivity for Synthesis;
Pergamon Press: Oxford, 2002; pp 73.
The method can be extended to o-methyl aromatic acids,
as seen in Scheme 3. Acids 10 and 12 are obtained in
1
0. Juaristi, E.; Beck, A. K.; Hansen, J.; Matt, T.; Muk-
hopedhyay, T.; Simon, M.; Seebach, D. Synthesis 1993,
1271.
5
7% and 70% yields, respectively. Unfortunately, reac-
tions with o-toluic and 2-methylnicotinic acids, under
different conditions, mainly led to the starting acid.
11. (a) Streitwieser, A.; Husemann, M.; Kim, Y.-J. J. Org.
Chem. 2003, 68, 7937; (b) Eames, J.; Suggate, M. J. Angew.
Chem., Int. Ed. 2005, 44, 186; (c) Scott, R.; Granader, J.;
Hilmersson, G. Chem. Eur. J. 2002, 8, 2081; (d) Sotoca, E.;
Bouillon, J. P.; Gil, S.; Parra, M.; Portella, C. Tetrahedron
In conclusion, we describe a general procedure for the
addition of dianions of carboxylic acids to bromoaceto-
nitrile. This methodology is a new approach from satu-
rated carboxylic acids to the synthesis of c-aminoacids
that are obtained in higher yields (around 75%) than
2
005, 61, 4395.
1
2. (a) Aurell, M. J.; Gil, S.; Mestres, R.; Parra, M.; Parra, L.
Tetrahedron 1998, 54, 4357; (b) Brun, E. M.; Gil, S.;
Mestres, R.; Parra, M. Tetrahedron 1998, 54, 15305; (c)
Brun, E. M.; Gil, S.; Mestres, R.; Parra, M. Synthesis
2000, 1160; (d) Brun, E. M.; Gil, S.; Mestres, R.; Parra, M.
Synlett 2001, 156.
7
those described. The method can be extended to unsat-
urated carboxylic acids.
1
3. (a) Brun, E. M.; Gil, S.; Mestres, R.; Parra, M. Synlett
Acknowledgements
1
999, 1088; (b) Brun, E. M.; Gil, S.; Mestres, R.; Parra, M.
Synthesis 2000, 273; (c) Brun, E. M.; Gil, S.; Parra, M.
Arkivoc 2002, 80.
The present research has been financed by DGCYT
(
CTQ2005-07562-C04-01/BQU) and by the Agencia
14. General procedure: n-BuLi (1.6 M in hexane, 5 mmol) was
introduced with stirring into a reaction flask that has been
purged. Hexane was evaporated under vacuum, the flask
cooled at À78 ꢁC and then THF (2 mL) was added to
redissolve the BuLi. Diethylamine (1 mmol) was added at
À78 ꢁC. The mixture was stirred for 15 min at 0 ꢁC. The
acid (2.25 mmol) in THF (2 mL) was added slowly at
À78 ꢁC. After 30 min at 0 ꢁC usually a clear solution of the
dianion was formed. Bromoacetonitrile (2.25 mmol) in
THF (2 mL) was added slowly at À78 ꢁC. The solution
was stirred at room temperature for 24 h and quenched
Valenciana de Ciencia y Tecnolog ´ı a (GV06/050).
References and notes
1
2
3
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with Et O (3 · 15 mL). The aqueous phase was acidified
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anhyd MgSO . After evaporation of the solvent, the
4
cyanoacids are obtained pure enough for the following
hydrogenation step.
15. (a) Brun, E. M.; Casades, I.; Gil, S.; Mestres, R.; Parra,
M. Tetrahedron Lett. 1998, 39, 5443; (b) Gil, S.; Torres,
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. Suman-Chauhan, N.; Webdale, L.; Hill, D. R.; Woodruff,
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44, 293.
5
. See for example: (a) Burgos-Lepley, C. E.; Thompson, L.
R.; Kneen, C. O.; Osborne, S. A.; Bryans, J. S.; Capiris,
T.; Suman-Chauhan, N.; Dooley, D. J.; Donovan, C. M.;
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S.; Parra, M. Tetrahedron: Asymmetry 2001, 12, 915.