Triethyl Methanetricarboxylate1

(1; R1 = R2 = Me)

[1186-73-8]  · C7H10O6  · Trimethyl Methanetricarboxylate  · (MW 190.17) (2; R1 = Me, R2 = Et)

[125563-04-4]  · C8H12O6  · Ethyl Dimethyl Methanetricarboxylate  · (MW 204.20) (3; R1 = Et, R2 = Me)

[124896-06-6]  · C9H14O6  · Diethyl Methyl Methanetricarboxylate  · (MW 218.23) (4; R1 = R2 = Et)

[6279-86-3]  · C10H16O6  · Triethyl Methanetricarboxylate  · (MW 232.26) (5; R1 = Et, R2 = t-Bu)

[71170-90-6]  · C12H20O6  · t-Butyl Diethyl Methanetricarboxylate  · (MW 260.32)

(masked malonate ester equivalent;2,3 regiospecific radical addition to terminal alkenes;4 MnIII-induced substitution on electron-rich aromatics5,6)

Physical Data: (1) bp 111-112 °C/4 mmHg; mp 45-46 °C; (2) bp 138-139 °C/12 mmHg; (3) bp 140-142 °C/12 mmHg; (4) bp 135-137 °C/12 mmHg; mp 27-29 °C; d 1.100 g cm-3.

Preparative Methods: methanetricarboxylate esters are generally prepared from appropriate malonate esters via formation of a metal salt and addition of an alkyl chloroformate (eq 1). Sodiomalonates work well for most esters (e.g. R1 = R2 = Me);7 however, magnesiomalonates generally provide better results for ethyl esters.8 Acylation of malonate esters has also been accomplished using Magnesium Oxide as the base,9 which is advantageous for the preparation of symmetric methanetricarboxylate esters (R1 = R2) because strictly anhydrous conditions are not required.

Trialkyl methanetricarboxylates are easily alkylated;1 facile dealkoxycarbonylation of these triesters has prompted their use as masked malonate esters.1,2,3 Conjugate addition (eq 2) of triethyl methanetricarboxylate occurs with a variety of Michael acceptors under phase-transfer conditions, providing a convenient two-carbon chain elongation.10

Trialkyl methanetricarboxylate radicals readily add to terminal alkenes, giving predominately the 1:1 adducts (50-75%).1,4 Unlike the radical additions of malonate or acetate esters to alkenes, the addition of methanetricarboxylate esters is regiospecific and limited exclusively to a-alkenes.4 Saponification of the 1:1 adduct, followed by decarboxylation, is a convenient route to n-alkylcarboxylic acids and is a two-carbon homologation of the starting alkene. Methanetricarboxylate esters also readily undergo manganese(III)-induced addition to electron-rich aromatic systems;5 this reactivity is attributed to the very electrophilic nature of the triester radical. This reaction was exploited to give the shortest, most efficient, reported synthesis of the analgesic ketorolac:6,11 three steps and 64% overall yield from 2-benzoylpyrrole (eq 3).

These triesters react with a variety of amines to give a broad range of products.1 Condensation of the triethyl ester with pyrazoles provided facile access to cross-conjugated mesomeric betaines without the use of chlorocarbonylketenes (eq 4).12

Pyrolysis of o-carboranes in the presence of trialkyl methanetricarboxylates produces 9-alkyl-o-carboranes in moderate yields, and represents one of the few reliable preparations of these molecules.13

Related Reagents.

Diethyl Malonate; Ethyl 3,3-Diethoxyacrylate; Diethyl Ethoxymagnesiomalonate; Ethyl Malonate; Ethyl Trimethylsilyl Malonate; Magnesium Ethyl Malonate; Malonic Acid; 2,2-Dimethyl-1,3-dioxane-4,6-dione.

1. Newkome, G. R.; Baker, G. R. OPP 1986, 18, 119.
2. Padgett, H. C.; Csendes, I. G.; Rapoport, H. JOC 1979, 44, 3492.
3. Brillon, D. SC 1986, 16, 291.
4. Vogel, H. H. S 1970, 99.
5. Cho, I.-S.; Muchowski, J. M. S 1991, 567.
6. Artis, D. R.; Cho, I.-S.; Muchowski, J. M. CJC 1992, 70, 1838.
7. Corson, B. B.; Sayre, J. L. OSC 1943, 2, 596.
8. Lund, H.; Voigt, A. OSC 1943, 2, 594.
9. Skarżewski, J. T 1989, 45, 4593.
10. Skarżewski, J. S 1990, 1125.
11. Artis, D. R.; Cho, I.-S.; Muchowski, J. M. CJC 1992, 70, 1838.
12. Kappe, T.; Kos, C. S 1989, 629.
13. Albagli, D.; Zheng, G.; Jones, M., Jr. IC 1986, 25, 129.

Gregory R. Baker & George R. Newkome

University of South Florida, Tampa, FL, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.