Methyl Chlorooxalate

[5781-53-3]  · C3H3ClO3  · Methyl Chlorooxalate  · (MW 122.51)

(acylating agent;1 heterocycle synthesis;2 deoxygenation intermediate;3 chiral a-hydroxy ketones4)

Alternate Names: MCO; methyl oxalyl chloride.

Physical Data: bp 118-120 °C; d 1.332 g cm-3.

Form Supplied in: liquid; commercially available.

Preparative Methods: originally prepared from methyl oxalate and phosphorus pentachloride,5 a simpler procedure involves treatment of crystalline potassium methyl oxalate with thionyl chloride and isolation of the product by distillation.6

Handling, Storage, and Precautions: corrosive liquid; lachrymator. Use in a fume hood.

Oxalyl Transfer.

Much of the chemistry of methyl chlorooxalate (MCO) is simply that of an acylating agent and parallels that of standard acid chlorides. Thus, in addition to acylating a variety of alcohols, this reagent has also been reported to acylate naphthols,1 indoles,7 and oxazoles.8 An interesting acylation of a 1-deoxy-1-diazo fructose derivative (1) with MCO provided the product (2) in 65% yield (eq 1).9 Attempts to use simpler acid chlorides (acetyl or benzoyl) for this chain elongation were not successful.

Heterocycle Synthesis.

Methyl chlorooxalate can be used to prepare a number of carboxy-substituted ring systems. For example, treatment of (3) with MCO in pyridine gave the isoflavone (4) in 66% yield (eq 2).2 Another interesting use of this reagent in an intramolecular cyclization is the reported construction of penems and carbapenems.10 Treatment of either (5a) or (5b) with Triethyl Phosphite provides the cyclized products (6a) and (6b) in 83% and 92% yields, respectively (eq 3). This reaction is thought to proceed by generation of a carbene intermediate. MCO has also been used for the construction of indole systems.11

Deoxygenation of Alcohols.

Methyl chlorooxalate has found use in the deoxygenation of tertiary and secondary alcohols.3 A number of gibberellic acid derivatives were acylated with this reagent under mild conditions without the use of base. The resulting methyl oxalyl esters were treated with Tri-n-butylstannane and 2,2-azo-2-methylpropionitrile in refluxing toluene to provide the deoxygenated products in good yield (eq 4).

Finally, an interesting application of this reagent for the preparation of chiral a-hydroxy ketones has recently been reported.4

1. Piccolo, O.; Filippini, L.; Tinucci, L.; Valoti, E.; Citterio, A. T 1986, 42, 885.
2. Farkas, L.; Gottsegen, A.; Nográdi, M. JCS(C) 1971, 1994.
3. Dolan, S. C.; MacMillan, J. CC 1985, 1588.
4. Flynn, G. A.; Beight, D. W. TL 1988, 29, 423.
5. Anschutz, R. LA 1889, 254, 1.
6. Southwick, P. L.; Seivard, L. L. JACS 1949, 71, 2532.
7. (a) Atta-ur-Rahman; Fatima, T.; Hasan, N. M. J. Chem. Soc. Pakistan 1989, 11, 24. (b) Leeson, P. D. JCS(P1) 1984, 2125.
8. Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P. JOC 1987, 52, 3413.
9. Meyer, B.; Kogelberg, H.; Koll, P.; Laumann, U. TL 1989, 30, 6641.
10. Kametani, T.; Chu, S.-D.; Itoh, A.; Wang, T.-C.; Nakayama, A.; Honda, T. CC 1988, 544.
11. Capuano, L.; Ahlhelm, A.; Hartmann, H. CB 1986, 119, 2069.

Michael D. Ennis

The Upjohn Company, Kalamazoo, MI, USA

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