Diethyl Ethylidenemalonate

[1462-12-0]  · C9H14O4  · Diethyl Ethylidenemalonate  · (MW 186.21)

(2,4-dienoates;1 Michael acceptor; 1,4-addition;2 [3 + 2] cycloaddition;3 cyclopropanes;4 cyclopentenes5)

Physical Data: bp 115-118 °C/17 mmHg; d 1.019 g cm-3.

Solubility: sol ethanol and diethyl ether.

Form Supplied in: colorless liquid; widely available.

Analysis of Reagent Purity: n20D = 1.4420.

Preparative Method: obtained by heating paraldehyde, Acetic Anhydride, and Diethyl Malonate.6

Purification: fractional vacuum distillation.

Handling, Storage, and Precautions: store at 5 °C. Use in a fume hood.

The reaction of diethyl ethylidenemalonate with benzaldehyde derivatives in the presence of methanolic Benzyltrimethylammonium Hydroxide (Triton B)1b or Tetramethylammonium Hydroxide1e yields methyl (2E,4E)-dienoates (eq 1).1 The reagent is used for the synthesis of cannabinoids.1a,c

Diethyl ethylidenemalonate reacts as a Michael acceptor with nucleophiles such as enolates,2d,p germanium-masked dienolates,2c acyl anions (thiazolium salt catalyzed; eq 2),2k organometallic compounds (Li,2m Mg,2q Mn,2e Cu,2a Zn2n,o), activated nitriles (ruthenium catalyzed),2f and lithium trialkylalkynylborates.2i,l

The 1,4-addition of crotylorganometallics of B, Ti, Zr, and Sn produces the anti adduct predominantly (eq 3).2g,h

Radicals such as the cyclohexyl radical, formed in situ by photolysis of the dicarbonyl(h5-cyclopentadienyl)iron dimer in the presence of cyclohexyl iodide, can be trapped by diethyl ethylidenemalonate to give the 1,4-addition products (eq 4).2b

Cyclopentenones are formed in a [3 + 2] cycloaddition with cyclopropenone acetals (see Diethyl Ethoxymethylenemalonate).3 The double bond of diethyl ethylidenemalonate can be cyclopropanated in high yield with Bromoform and Sodium Hydroxide in the presence of benzyltriethylammonium chloride (2) (eq 5).4 Cyclopentene derivatives can be obtained in moderate yields by treatment of diethyl ethylidenemalonate with propargyl bromides and zinc in THF at low temperature (eq 6).5

Dialkyl benzylidenemalonates obtained by Knoevenagel reaction7 of dialkyl malonates and benzaldehyde are useful substrates for the synthesis of dialkyl mesoxalates by ozonolysis.8

Related Reagents.

Diethyl Ethoxymethylenemalonate; Diethyl Malonate; Diethyl Methylenemalonate; 2,2-Dimethyl-1,3-dioxane-4,6-dione; Methyl 6-Oxo-1-cyclohexenecarboxylate.

1. (a) Crombie, L.; Crombie, W. M. L.; Tuchinda, P. JCS(P1) 1988, 1255. (b) Dallacker, F.; Tumbrink, L. ZN(B) 1984, 39, 925. (c) Crombie, L.; Crombie, W. M. L.; Kilbee, G. W.; Tuchinda, P. TL 1979, 4773. (d) Horton, W. J.; Pitchforth, L. L. JOC 1960, 25, 131. (e) Gardner, P. D.; Horton, W. J.; Thompson, G.; Twelves, R. R. JACS 1952, 74, 5527.
2. (a) Cahiez, G.; Venegas, P.; Tucker, C. E.; Majid, T. N.; Knochel, P. CC 1992, 1406. (b) Giese, B.; Thoma, G. HCA 1991, 74, 1135. (c) Yamamoto, Y.; Okano, H.; Yamada, J.-I. TL 1991, 32, 4749. (d) Robl J. A. TL 1990, 31, 3421. (e) Cahiez, G.; Alami, M. T 1989, 45, 4163. (f) Naota, T.; Taki, H.; Mizuno, M.; Murahashi, S.-I. JACS 1989, 111, 5954. (g) Yamamoto, Y.; Nishii, S. JOC 1988, 53, 3597. (h) Yamamoto, Y.; Nishii, S.; Maruyama, K. CC 1985, 386. (i) Pelter, A.; Hughes, L.; Rao, J. M. JCS(P1) 1982, 719. (k) Stetter, H.; Jonas, F. CB 1981, 114, 564. (l) Pelter, A.; Rao, J. M. TL 1981, 22, 797. (m) Trost, B. M.; Chan, D. M. T. JACS 1981, 103, 5972. (n) Bellassoued, M.; Frangin, Y.; Gaudemar, M. S 1977, 205. (o) Gaudemar-Bardone, F.; Gaudemar, M. BSF(2) 1973, 12, 3467. (p) Sato, K.; Kurihara, Y.; Inoue, S. BCJ 1967, 40, 942. (q) Holmberg, G.-A. ACS 1958, 12, 229.
3. (a) Tokuyama, H.; Isaka, M.; Nakamura, E. JACS 1992, 114, 5523. (b) Boger, D. L.; Brotherton, C. E. JACS 1986, 108, 6695. (c) Boger, D. L.; Brotherton, C. E. JACS 1984, 106, 805.
4. Baird, M. S.; Gerrard, M. E. TL 1985, 26, 6353.
5. Bellassoued, M.; Frangin, Y.; Gaudemar, M. S 1978, 150.
6. Fones, W. S. OSC 1963, 4, 293.
7. Tietze, L. F.; Beifuss, U. COS 1991, 2, 341.
8. Tietze, L. F.; Bratz, M. OS 1992, 71, 214.

Lutz F. Tietze & Holger Geissler

Georg-August-Universität zu Göttingen, Germany

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