Methyl Magnesium Carbonate1

[4861-79-4]  · C3H6MgO4  · Methyl Magnesium Carbonate  · (MW 130.40)

(agent for the a-carboxylation of nitroalkanes, ketones, lactones, hydantoins, and phenols1)

Alternate Name: MMC.

Preparative Methods: prepared in situ by saturating a solution (2 M) of Magnesium Methoxide in DMF with Carbon Dioxide.3 It is assumed to have the formula MeOMgOCO2Me.(CO2)n where n varies with temperature and solvent.2

Carboxylation of Nitroalkanes and Ketones.

Stiles and Finkbeiner discovered that methyl magnesium carbonate readily carboxylated nitroalkanes at the a-position (eq 1).2 They concluded that the reaction proceeds to give a magnesium chelate which confers stability on the products (eq 2).4 The procedure has recently been used to prepare isotopically labelled a-oxoglutaric acid from [13C]nitromethane.5

MMC has also been used to carboxylate ketones (eqs 3 and 4), although quite vigorous conditions (100-130 °C) are required.6 The process is considered to be reversible and results in the carboxy group occupying the less hindered location. It is thus highly selective for carboxylation at the terminal methyl group of 2-alkanones.7 Carboxylation at a methine site has not been observed. b-Tetralones, which might have been expected to undergo carboxylation at the more acidic C-1 position, afford the C-3 isomers (eq 5) since the peri interaction between the aromatic ring and a carboxy group at C-1 would be destabilizing.8

The carboxylation of hydrindenones with MMC (eq 6) was observed to take a very different course9,10 from that experienced with the equivalent octalone (eq 7)9 and with cholest-4-en-3-one (eq 8).11 The difference was attributed to a preference for heteroannular dienolate formation in the hydrindene substrate, relative to the decalin systems. Carboxylation of a ketone, used as an intermediate in the synthesis of quassins, failed when a neighboring acetoxy group underwent hydrolysis. When the interfering hydroxy was protected as a TBDMS or THP ether, however, an excellent yield of the desired product was obtained (eq 9).12

Carboxylation and a-Methylenation of Lactones.

Lactones are readily carboxylated with MMC and the higher stability of the products, relative to those from ketones, ensures generally excellent yields (eq 10).13 The carboxylic acid products may be used in a particularly efficaceous preparation of a-methylene lactones with formaldehyde (eq 11)14 or Eschenmoser's salt (eq 12).15

During the synthesis of protolichesterinic acid, the carboxylation failed on a lactone substrate bearing a methoxycarbonyl substituent, but the reaction proceeded satisfactorily with the parent acid (eq 13).16

Miscellaneous Carboxylations.

Hydantoins are readily carboxylated with MMC (eq 14) and the products may be alkylated in situ (eq 15).17 The carboxylation of resorcinols has been reported, including a phenolic intermediate in the synthesis of cannabinoids (eq 16).18

Related Reactions.

Modest yields have been obtained from the carboxylation of ketones with a 2:1 complex of potassium phenoxide and CO2,19 and with the complexes (1),20 (2),21 (3),22 and (4).23 However, the ureide complexes (5)24 afforded significantly improved yields, as does a mixture of Triethylamine with Magnesium Iodide (prepared in situ from MgCl2 and NaI) in acetonitrile.25 This last magnesium carbamate differs from the others in allowing carboxylation at methine positions, as in dimethylcyclohexanone (65% yield) and isobutyrophenone (90% yield).

Related Reagents.

Carbon Dioxide; Carbon Oxysulfide; N,N-Carbonyldiimidazole; Diethyl Carbonate; Methyl Chloroformate; Methyl Cyanoformate.

1. (a) House, H. O. Modern Synthetic Reactions, Benjamin: Menlo Park, 1972; pp 758-759. (b) Haruki, E. In Organic and Bio-organic Chemistry of Carbon Dioxide, Inoue, S., Ed.; Wiley: New York, 1982; pp 7-9.
2. (a) Finkbeiner, H. L.; Stiles, M. JACS 1959, 81, 505. (b) Finkbeiner, H. L.; Wagner, G. W. JOC 1963, 28, 215; Finkbeiner, H. L.; Stiles, M. JACS 1963, 85, 616.
3. Steinkopf, W. CB 1909, 42, 3925.
4. Finkbeiner, H. L.; Stiles, M. JACS 1963, 85, 616.
5. Baldwin, J. E.; Adlington, R. M.; Schofield, C. J.; Sobey, W. J.; Wood, M. E. CC 1989, 1012.
6. Stiles, M. JACS 1959, 81, 2598.
7. (a) Crombie, L.; Hemesley, P.; Pattenden, G. TL 1968, 3021. (b) Whitlock, B. J.; Whitlock, H. W., Jr. JOC 1974, 39, 3144.
8. Pelletier, S. W.; Chappell, R. L.; Parthasarathy, P. C.; Lewin, N. JOC 1966, 31, 1747.
9. Micheli, R. A.; Hajos, Z. G.; Cohen, N.; Parrish, D. R.; Portland, L. A.; Sciamanna, W.; Scott, M. A.; Wehrli, P. A. JOC 1975, 40, 675.
10. (a) Rychnovsky, S. D.; Mickus, D. E. JOC 1992, 57, 2732. (b) Isaacs, R. C. A.; Di Grandi, M. J.; Danishefsky, S. J. JOC 1993, 58, 3938.
11. Huynh, C.; Julia, S. BSF 1972, 1794.
12. Kerwin, S. M.; Paul, A. G.; Heathcock, C. H. JOC 1987, 52, 1686.
13. Martin, J.; Watts, P. C.; Johnson, F. CC 1970, 27.
14. Parker, W. L.; Johnson, F. JOC 1973, 38, 2489.
15. Lansbury, P. T.; Vacca, J. P. T 1982, 38, 2797.
16. Martin, J.; Watts, P. C.; Johnson, F. JOC 1974, 39, 1676.
17. Finkbeiner, H. L. JOC 1965, 30, 3414.
18. Mechoulam, R.; Ben-Zvi, Z. CC 1969, 343.
19. Mori, H.; Yamamoto, H.; Kwan, T. CPB 1972, 20, 2440.
20. Matsumura, N.; Ohba, T.; Yoneda, S. CL 1983, 317.
21. Matsumura, N.; Sakaguchi, Y.; Ohba, T.; Inoue, H. CC 1980, 326.
22. Tsuda, T.; Chujo, Y.; Hayasaki, T.; Saegusa, T. CC 1979, 797.
23. Matsumura, N.; Ohba, T.; Inoue, H. BCJ 1982, 55, 3949.
24. (a) Sakurai, H.; Shirahata, A.; Hosomi, A. TL 1980, 1967. (b) Matsumura, N.; Asai, N.; Yoneda, S. CC 1983, 1487.
25. Tirpak, R. E.; Olsen, R. S.; Rathke, M. W. JOC 1985, 50, 4877.

Lewis N. Mander

The Australian National University, Canberra, Australia

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