LETTER
Mild Hydrohalogenation of 3-Propynamides
91
Sulikowski, G. A. Tetrahedron Lett. 2001, 42, 6621.
(c) Mori, M.; Nakanishi, M.; Kajishima, D.; Sato, Y. J. Am.
Chem. Soc. 2003, 125, 9801.
1) ZnI2 (2 equiv)
t-BuI (3 equiv)
O
I
O
R
O
CH2Cl2, 18 h, r.t.
R
O
(3) Ikoma, M.; Oikawa, M.; Sasaki, M. Tetrahedron 2008, 64,
2) H2O
2740.
4a–d
5a–d
(4) Han, C.; Shen, R.; Su, S.; Porco, J. A. Jr. Org. Lett. 2004, 6,
27.
(5) (a) Bey, P.; Vevert, J. P. J. Org. Chem. 1980, 45, 3249.
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Mons, S.; Delpech, B.; Marazano, C. Eur. J. Org. Chem.
2006, 4106.
4a, R = Allyl
5a, 50%
5b, 94%
5c, 87%
5d, 62%
4b, R = Bn
4c, R = (CH2)3Ph
4d, R =
CH2
H
Scheme 5 Hydroiodination of propiolic esters
(6) For the preparation of (E)-3-bromopropenamides via the
reaction of 3-aminopropynal with HBr followed by
rearrangement, see: (a) Neuenschwander, M.; Hafner, K.
Angew. Chem., Int. Ed. Engl. 1968, 7, 460. (b) Gais, H.-J.;
Hafner, K.; Neuenschwander, M. Helv. Chim. Acta 1969, 52,
2641. (c) Niederhauser, A.; Neuenschwander, M. Helv.
Chim. Acta 1973, 56, 1318. For the synthesis of (E)- or (Z)-
iodopropenamides via peptide coupling reaction between the
corresponding (E)- or (Z)-iodopropenoic acids and an amine,
see refs. 1d, 3, 4. For aminolysis of acyl chlorides prepared
from 3-bromo- or 3-iodopropenoic acids leading to a
mixture of Z- and E-isomers, see: (d) Wilson, R. M.;
Commons, T. J. J. Org. Chem. 1975, 40, 2891. (e) Wojcik,
J.; Witanowski, M. J. Mol. Struct. 1978, 49, 249.
(7) Fujisawa, T.; Tanaka, A.; Ukaji, Y. Chem. Lett. 1989, 1255.
(8) (a) Ma, S.; Lu, X. Tetrahedron Lett. 1990, 31, 7653.
(b) Ma, S.; Lu, X.; Li, Z. J. Org. Chem. 1992, 57, 709. (c)
For the use of NaI in AcOH, see: Marek, I.; Alexakis, A.;
Normant, J.-F. Tetrahedron Lett. 1992, 33, 5329.
(9) The reactions were generally performed at 90 °C over 22–48
h. At 70 °C lower yields were obtained (see ref. 8b).
(10) Feray, L.; Bertrand, M. P. Eur. J. Org. Chem. 2008, 3164.
(11) Using only 2 equivalents of tert-butyl iodide led to lower
yields.
Finally, 1-phenylprop-2-yn-1-one was tested as substrate
(Scheme 6). In this case the reaction led exclusively to the
E-isomer. However, the yield was rather low. It is known
from previous work that in this case the Z-isomer is slowly
converted into the E-isomer on standing at 35 °C.8b
O
1) ZnI2 (2 equiv)
t-BuI (3 equiv)
CH2Cl2, 18 h, r.t.
O
I
2) H2O
40%
6
7
Scheme 6 Hydroiodination of 1-phenylprop-2-yn-1-one
In conclusion, we have shown that the couple zinc halide
and tert-butyl halide could be used to prepare stereoselec-
tively (Z)-halopropenamides under very mild conditions.
High yields were obtained at room temperature whatever
the substitution of the amide. This mild methodology, also
suitable to prepare 3-halopropenoates, offers an alterna-
tive to the most commonly used procedures.
(12) De la Pradilla, R. F.; Morente, M.; Paley, R. S. Tetrahedron
Lett. 1992, 33, 6101.
(13) This might be correlated to the relative basicity of amides
and sulfoxides.
(14) (Z)-N,N-Diallyl-3-iodoacrylamide(2d); Typical
Procedure
References and Notes
(1) For Sonogashira coupling reaction, see: (a) Eichberg, M. J.;
Dorta, R. L.; Grotjahn, D. B.; Lamottke, K.; Schmidt, M.;
Vollhardt, K. P. C. J. Am. Chem. Soc. 2001, 123, 9324.
(b) Fiandanese, V.; Babudri, F.; Marchese, G.; Punzi, A.
Tetrahedron 2002, 58, 9547. (c) Cherry, K.; Thibonnet, J.;
Duchêne, A.; Parrain, J.-L.; Abarbri, M. Tetrahedron Lett.
2004, 45, 2063. (d) Cramer, N.; Laschat, S.; Baro, A.;
Schwalbe, H.; Richter, C. Angew. Chem. Int. Ed. 2005, 44,
820. (e) Cramer, N.; Buchweitz, M.; Laschat, S.; Frey, W.;
Baro, A.; Mathieu, D.; Richter, C.; Schwalbe, H. Chem. Eur.
J. 2006, 12, 2488. For Stille coupling reaction, see:
(f) Mcdonald, G.; Alcaraz, L.; Wei, X.; Lewis, N. J.; Taylor,
R. J. K. Tetrahedron 1998, 54, 9823. (g) Cherry, K.;
Abarbri, M.; Parrain, J.-L.; Duchêne, A. Tetrahedron Lett.
2003, 44, 5791. (h) Cherry, K.; Duchêne, A.; Thibonnet, J.;
Parrain, J.-L.; Abarbri, M. Synthesis 2005, 2349. For
coupling reaction with organozirconocenes, see:
To a solution of N,N-diallyl-3-propynamide (50 mg, 0.335
mmol) in CH2Cl2 (1.7 mL) were added t-BuI (200 mL, 1.67
mmol, 3 equiv) and ZnI2 (214 mg, 0.67 mmol, 2 equiv) at r.t.
After 18 h, H2O (5 mL) was added, and the reaction mixture
was extracted twice with CH2Cl2. The organic layers were
dried over MgSO4, filtered, and concentrated under reduce
pressure. Flash chromatography on SiO2 (100% pentane
then 100% Et2O) afforded 2d (81 mg, 0.293 mmol, 87%). 1H
NMR (300 MHz): d = 3.85 (br d, J = 5.1 Hz, 2 H), 4.05 (br
d, J = 5.9 Hz, 2 H), 5.11–5.28 (m, 4 H), 5.68–5.89 (m, 2 H),
6.85 (d, J = 8.8 Hz, 1 H), 7.10 (d, J = 8.8 Hz, 1 H). 13C NMR
(75 MHz): d = 47.4 (CH2), 49.9 (CH2), 87.6 (=CHI), 117.9
(=CH2), 118.4 (=CH2), 132.9 (=CH), 133.1 (=CH), 134.5
(=CH), 167.1 (C=O). HRMS: m/z calcd for C9H12NOI
[MH]+: 278.0036; found: 278.0035.
(15) Taniguchi, M.; Kobayashi, S.; Nakagawa, M.; Hino, T.
(i) Crombie, L.; Hobbs, A. J. W.; Horsham, M. A.
Tetrahedron Lett. 1986, 27, 4763.
Tetrahedron Lett. 1987, 28, 4875. (j) Rossi, R.; Carpita, A.;
Lippolis, V. Synth. Commun. 1991, 21, 333. For annulation
of allenes, see: (k) Larock, R. C.; He, Y.; Leong, W. W.;
Han, X.; Refvik, M. D.; Zenner, J. M. J. Org. Chem. 1998,
63, 2154.
(16) Owing to complexation of the product to zinc salts, the
olefinic protons are more deshielded in the crude reaction
mixture – before aqueous treatment – than in the pure
isolated product 2d (d = 7.0 ppm and 7.4 ppm with a
coupling constant equal to 9.1 Hz: 6.85 ppm and 7.10 ppm
with a coupling constant equal to 8.8 Hz, respectively).
(17) Using zinc bromide led to degradation of benzylic and
propargylic esters.
(2) (a) Grigg, R.; Sridharan, V.; Stevenson, P.; Sukirthalingam,
S. Tetrahedron 1989, 45, 3557. (b) Kiewel, K.; Tallant, M.;
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