PAPER
Simple and Direct Access to Ethylidene Malonates
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was stirred for 10 min at 20 °C under N2. Then, acetaldehyde (1.1
mL, 20 mmol) was added in one portion through the vapor condens-
er and the solution was stirred at 80 °C for 10 min. The reaction
mixture was allowed to cool at r.t. and slowly decomposed in a sat.
solution of Na2CO3 (25 mL). The aqueous phase was extracted with
Et2O (2 × 15 mL) and the combined organic phases were washed
with brine and, after drying, were evaporated under reduced pres-
sure. The residue was purified using flash chromatography (eluent:
EtOAc–cyclohexane, 15:85); yield: 84%; colorless solid; mp 110
°C.
(3) Also see: Jabin, I.; Revial, G.; Monnier-Benoit, N.;
Netchitailo, P. J. Org. Chem. 2001, 66, 256.
(4) (a) For a review, see: Jones, G. In Organic Reactions, Vol.
15; Wiley: New York, 1967, 204. (b) Brettle, R. In
Comprehensive Organic Chemistry, Vol. 1; Stoddart, J. F.,
Ed.; Pergamon Press: Oxford UK, 1979, 943; see page 967.
(c) Tiezte, L. F.; Beifuss, U. In Comprehensive Organic
Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press:
Oxford UK, 1991, 341.
(5) Chodroff, S.; Whitmore, W. F. J. Am. Chem. Soc. 1950, 72,
1073.
IR (neat): 1744, 1590, 1484, 1158, 1130, 815, 734, 684, cm–1.
(6) See for example: Cardillo, G.; Fabbroni, S.; Gentilucci, L.;
Gianotti, M.; Tolomelli, A. Synth. Commun. 2003, 33, 1587.
(7) (a) Kaupp, G.; Naimi-Jamal, M. R.; Schmeyers, J.
Tetrahedron 2003, 59, 3753. (b) McCluskey, A.; Robinson,
P. J.; Hill, T.; Scott, J. L.; Edwards, J. K. Tetrahedron Lett.
2002, 43, 3117.
(8) (a) Texier-Boulet, F.; Foucaud, A. Tetrahedron Lett. 1982,
23, 4927. (b) Cooke, G.; Palmer, H. M.; Schultz, O. Synth.
Commun. 1996, 2549. (c) Cabello, J. A.; Campelo, J. M.;
Garcia, A.; Luna, D.; Marinas, J. M. J. Org. Chem. 1984, 49,
5195. (d) Angeletti, E.; Canapa, C.; Martinetti, G.;
Venturello, P. Tetrahedron Lett. 1993, 34, 7437.
(9) Brufola, G.; Fringuelli, F.; Piernatti, O.; Pizzo, F.
Heterocycles 1997, 45, 1715.
(10) (a) Mitra, A. K.; De, A.; Karchaudhuri, N. Synth. Commun.
1999, 29, 2731. (b) Cherouvrier, J. R.; Boisset, J.; Carreaux,
F.; Bazureau, J. P. Green Chem. 2001, 3, 165.
(11) Jenner, G. Tetrahedron Lett. 2001, 42, 243.
(12) Morrisson, D. W.; Forbes, D. C.; Davis, J. H. Jr.
Tetrahedron Lett. 2001, 42, 6053.
1H NMR (200 MHz, CDCl3): d = 1.64 (d, 3J = 7.0 Hz, 3 H, CH3),
3
3
3.57 (q, J = 7.0 Hz, 1 H, CHCH3), 4.44 (d, J = 7.0 Hz, 2 H,
CH2CHCH3), 7.22–7.52 (m, 20 H, HAr).
13C NMR (50 MHz, CDCl3): d = 14.8 (CH3), 33.1 (CHCH3), 54.3
(2 × CH, CH2CHCH3), 121.3 (8 × CH, CHo-Ar), 126.4 (4 × CH,
CHp-Ar), 129.6 (8 × CH, CHm-Ar), 150.3 (4 × C, CAr), 166.3 (2 × C,
CO), 166.8 (2 × C, CO).
Anal. Calcd for C32H26O8 (538.54): C, 71.37; H, 4.87. Found: C,
71.15; H, 4.95.
Synthesis of 2-(1-Hydroxyethyl)malonic Acid Dimethyl Ester
(4b)21
A suspension of alumina (1.02 g, 10 mmol), dimethyl malonate
(264 mg, 2 mmol) and acetaldehyde (176 mg, 0.22 mL, 4 mmol) in
CH2Cl2 (4 mL) was stirred at 20 °C for 24 h (the reaction progress
was monitored by 1H NMR). The mixture was filtered over a pad of
celite, the filtrate was concentrated in vacuo and the residue was pu-
rified by flash chromatography on alumina (cyclohexane–EtOAc,
8:2); yield: 81%; colorless oil.
(13) (a) Liu, H. N.; Auchus, R.; Walsh, C. T. J. Am. Chem. Soc.
1984, 106, 5335. (b) Ishida, A.; Yamashita, S.; Takamuku,
S. Bull. Chem. Soc. Jpn. 1988, 61, 2229.
(14) (a) Lehnert, W. Tetrahedron Lett. 1970, 34, 4723.
(b) Lehnert, W. Tetrahedron 1972, 28, 663. (c) Lehnert, W.
Tetrahedron 1973, 29, 635. (d) Compare: Jones, G. Org.
React. (N.Y.) 1967, 15, 204.
IR (neat): 3530, 2958, 2851, 1731 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.09 (d, 3J = 6.4 Hz, 3 H, CH3CH),
3.25 (d, 3J = 6.9 Hz, 1 H, CHCH3), 3.26 (br s, 1 H, OH), 3.57 (s, 3
H, CH3O), 3.59 (s, 3 H, CH3O), 4.18 (p, 3J = 6.6 Hz, 1 H, CHCH3)
13C NMR (50 MHz, CDCl3): d = 20.3 (CH3CH), 52.0 (2 × OCH3),
58.4 (CHCH3), 66.2 (CHOH), 167.9 (CO), 168.5 (CO).
HRMS (ESI): m/z [M + Na+] calcd for C7H12O5Na: 199.0582;
found: 199.0576.
(15) Taken from the web page available at:
(16) Weir, M. R. S.; Hyne, J. B. Can. J. Chem. 1965, 43, 772.
(17) Prajapati, G.; Lekhok, K. C.; Sandhu, J. S.; Ghosh, A. C. J.
Chem. Soc., Perkin Trans 1 1996, 959.
(18) (a) Wingler, F.; Reiff, H. Liebigs Ann. Chem. 1967, 705, 96.
(b) Yamamoto, Y.; Nishii, S. J. Org. Chem. 1988, 53, 3597.
(c) Bogdanov, V. S.; Ugrak, B. I.; Krasnaya, Z. A.;
Stytsenko, T. S. Bull. Acad. Sci. USSR, Div. Chem. Sci.
(Engl. Transl.) 1990, 298.
(19) For a synthesis and reactivity of aldol 4c, see for example:
(a) Roesch, A. Bull. Soc. Chim. 1937, 4, 1643. (b) Brink,
M.; Schjanberg, E. J. Prakt. Chem. 1980, 685. (c) Ref. 13b.
(20) Lopez Giral, A.; Mahuteau-Betzer, F.; Gateau-Olesker, A.;
Marazano, C. Eur. J. Org. Chem. 2003, 1859.
(21) Doleschall, G. Acta Chim. Hung. 1991, 128, 823.
(22) Bégué, J.-P.; Bonnet-Delpon, D.; Crousse, B. Synlett 2004,
18.
(23) (a) A partial conversion was observed after 12 h at 80 °C
(1a:7 = 3:1). No trace of ethylidene diacetate 5 could be
detected in the crude. (b) Cardillo, G.; Gentilucci, L.;
Gianotti, M.; Perciaccante, R.; Tolomelli, A. J. Org. Chem.
2001, 66, 8657. (c) Tsuboi, S.; Wada, H.; Murakana, K.;
Takeda, A. Bull. Chem. Soc. Jpn. 1987, 60, 2917.
(24) (a) Matsuki, T.; Hu, N. X.; Aso, Y.; Otsubo, T.; Ogura, F.
Bull. Chem. Soc. Jpn. 1989, 62, 2105. (b) Niwayama, S.;
Houk, K. N.; Kusumi, T. Tetrahedron Lett. 1994, 35, 527.
Acknowledgment
This work was supported by the CNRS and the MENRT. We thank
Michèle Ourevitch (CNRS, BioCIS, Châtenay-Malabry, France)
for NMR assistance and Sophie Mairesse-Lebrun (CNRS, BioCIS,
Châtenay-Malabry, France) for elemental analyses.
References
(1) (a) d’Angelo, J.; Desmaële, D.; Dumas, F.; Guingant, A.
Tetrahedron: Asymmetry 1992, 3, 459. (b) d’Angelo, J.;
Cavé, C.; Desmaële, D.; Dumas, F. In Trends in Organic
Chemistry, Vol. 4; Pandalai, S. G., Ed.; Trivandrum: India,
1993, 555.
(2) (a) Camara, C.; Joseph, D.; Dumas, F.; d’Angelo, J.;
Charoni, A. Tetrahedron Lett. 2002, 42, 1445. (b) de
Oliveira, E. R.; Miet, C.; d’Angelo, J.; Dumas, F. In
Chemical Processes and Reactions under Extreme or Non-
Classic Conditions; Luche, J. L.; Balny, C.; Benefice, S.;
Denis, J. M.; Pétrier, C., Eds.; Office for Official
Publications of the European Communities: Luxembourg,
1998, 97. (c) Camara, C.; Keller, L.; Jean-Charles, K.;
Joseph, D.; Dumas, F. High Pres. Res. 2004, 24, 149.
Synthesis 2006, No. 6, 1045–1049 © Thieme Stuttgart · New York