Magnesium Ethyl Malonate1

[64679-38-5]  · C5H6MgO4  · Magnesium Ethyl Malonate  · (MW 154.42)

(reagent for conjugate addition to a,b-unsaturated carbonyl compounds followed by in situ decarboxylation to give 1,5 keto-esters;2 conjugate addition to other functionality;2 acylation of active esters1,3)

Alternate Name: MEM.

Physical Data: high melting solid salt; ethanol complex.

Solubility: sol DMF; slightly sol THF.

Form Supplied in: off-white solid or slurry in THF.

Analysis of Reagent Purity: 1H NMR. Drying: azeotrope with benzene or toluene; high vacuum.

Handling, Storage, and Precautions: hygroscopic solid; stable for at least several weeks as a solid or slurry in dry THF.

Introduction.

Magnesium ethyl malonate (1) undergoes conjugate addition reactions with a,b-enones and other activated alkenes,2 as well as acylation of active esters.1,3 Decarboxylation occurs upon neutralization with acetic acid or during workup, affording a single-step addition of an acetic ester residue. Ethyl Malonate reacts with magnesium metal turnings in ethanol to give (1), a basic salt, complexed with 1 equiv of ethanol (eq 1) or with isopropylmagnesium bromide to form a bromide complex.1

Dilithio ethyl malonate undergoes alkylation with alkyl halides and subsequent decarboxylation (eq 2).4 Little or no reaction occurs with ketones or enones.

Conjugate Additions.

As the magnesium salt, (1) gives exclusive conjugate, 1,4 addition to a,b-enones, probably due to the reversibility of 1,2-addition (eq 3).2 Steric hindrance at either the a- or b-position can inhibit addition of (1) and starting material is then recovered.2 Conjugate addition of (1) to 6-methyl-2-cyclohexenone occurs with stereoselection (axial attack) (eq 4).5 Other a,b-unsaturated electron-withdrawing groups give conjugate addition with (1) (eqs 5-7).2,6

Acylations.

Magnesium ethyl malonate adds the acetic ester residue to activated carboxylic acid derivatives, acid chlorides (eq 8),1,3a acyl imidazolides (eqs 9-12),1,3b-f and mixed anhydrides (eq 11).3b Decarboxylation is more facile after acylation with (1) than after conjugate addition and does not require prolonged treatment after neutralization with acetic acid.

Electrophiles such as (methylthio)alkylideniminium salts react with (1) to give the expected addition products (eq 13).7

Analogous Magnesium Malonates.

The neutral magnesium carboxylate salt of S-thioethyl methylthiomalonate has been prepared and added to acyl imidazolides (eq 14).8 The methyl ester analog of (1) is also reactive (eq 15).8

Related Reagents.

Bis(trimethylsilyl) Malonate; Diethyl Ethoxymagnesiomalonate; Diethyl Malonate; 2,2-Dimethyl-1,3-dioxane-4,6-dione; Ethyl Bromozincacetate; Ethyl Lithioacetate; Ethyl Lithio(trimethylsilyl)acetate; Ethyl Malonate; Ethyl Trimethylsilylacetate; Ethyl Trimethylsilyl Malonate.


1. (a) Ireland, R.; Marshall, J. JACS 1959, 81, 2907. (b) Bram, G.; Vilkas, M. BSF 1964, 945.
2. (a) McMurry, J. E.; Andrus, W. A.; Musser, J. H. SC 1978, 8, 53. (b) Fang, J. M. JOC 1982, 47, 3464. (c) Bailey, W. F.; Nurmi, T. T.; Patricia, J. J.; Wang, W. JACS 1987, 109, 2442. (d) Bailey, W. F.; Khanolkar, A. D. JOC 1990, 55, 6058.
3. (a) Pollet, P.; Gelin, S. S 1978, 142. (b) Hankovszky, H. O.; Hideg, K.; Lex, L.; Kulcsar, G.; Halasz, H. A. CJC 1982, 60, 1432. (c) Batty, D.; Crich, D. JCS(P1) 1992, 3205. (d) Houghten, R. A.; Simpson, R. A.; Hanson, R. N.; Rapoport, H. JOC 1979, 44, 4536. (e) Schroeder, M. C.; Kiely, J. S.; Johnson, D. R.; Szoteck, D. L.; Domagala, J. M. Stickney, T. M.; Michel, A.; Kampf, J. M. JHC 1992, 29, 1481. (f) Gumieniak, J.; Andruszkiewicz, R.; Borowski, E. Pol. J. Chem. 1984, 58, 881.
4. McMurry, J. E.; Musser, J. H. JOC 1975, 40, 2556.
5. Bohlmann, F.; Suding, H. LA 1985, 160.
6. (a) Schlessinger, R. H.; Wood, J. L. JOC 1986, 51, 2621. (b) Denmark, S. E.; Weber, E. J. HCA 1983, 66, 1655.
7. Gugelchuk, M. M.; Hart, D. J.; Tsai, Y. M. JOC 1981, 46, 3671.
8. Brooks, D. W.; Lu, L. D.-L.; Masamune, S. AG(E) 1979, 18, 72.

Alex Andrus

Applied Biosystems, Foster City, CA, USA



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