Dimethyl Diazomethylphosphonate

(R = Me)

[27491-70-9]  · C3H7N2O3P  · Dimethyl Diazomethylphosphonate  · (MW 150.09) (R = Et)

[25411-73-8]  · C5H11N2O3P  · Diethyl Diazomethylphosphonate  · (MW 178.15)

(bifunctional reagents capable of Horner-Wadsworth-Emmons and carbene chemistry;6 conversion of aldehydes to terminal alkynes;6a preparation of vinyl ethers10 and enamines;11 cyclopropanation of alkenes;20 cycloaddition to furnish heterocycles21)

Alternate Name: DAMP.

Physical Data: (R = Me) bp 59 °C/0.1 mmHg; n25D 1.4585. (R = Et) bp 86-88 °C/0.2 mmHg; n25D 1.4503.

Solubility: insol H2O; sol MeOH, THF, toluene.

Preparative Methods: for the most part, the reagents have been prepared by the method of Seyferth,1 a convenient three-step sequence beginning with commercially available N-(bromomethyl)phthalimide. More recently, two alternatives have been detailed, both of which appear to offer synthetic utility.2

Handling, Storage, and Precautions: stable indefinitely when stored at 4 °C under argon. Caution: All distillations should be carried out behind a blast shield.

Preparation of Diazo Phosphonates.

Diethyl (diazomethyl)phosphonate is readily lithiated (n-Butyllithium, THF, -100 °C) and the resulting lithio derivative can be acylated (PhCOBr, 33%) (eq 1) or silylated (poor yield).3 The corresponding silver derivative, formed by treatment with Silver(I) Oxide, can be alkylated with reactive allylic halides.3 a-Diazo-b-hydroxy phosphonates result when the lithio derivative is treated with aryl aldehydes; alternatively they can be prepared by direct reaction of DAMP with aldehydes in the presence of Triethylamine (eq 2).4

Insertion Reactions.

The reagents, with Lewis acid catalysis, insert smoothly into readily fissile bonds. Thus aldehydes are converted into b-keto phosphonates5 on treatment with the reagents and Tin(II) Chloride (eq 3).

Tandem Horner-Wadsworth-Emmons Carbene Reactions.

Carbonyl groups, on treatment with the anion of the reagents, are smoothly converted into intermediate vinyl carbene species.6,9 In the case of ketones, one of three pathways is then followed. The first is a [1,2]-aryl shift which may occur to form an internal alkyne (eq 4).6a,7 Reports indicate that, for the most part, this shift does not occur with transfer of an alkyl group.8 The second possibility occurs when an abstractable hydrogen is available, into which bond the carbene inserts.9 Examples of this chemistry abound; the method is useful for furnishing vinyl ethers (eq 5),2b,6b,10 enamines (eq 5),6b,11 cyclic alkenes (eq 6),9,12,13 furans,14 and other heterocycles (eq 7).15 A recent example describes possible limitations of this technology, however; use of Trimethylsilyldiazomethane offers some improvement.12b Here, the alkenation sequence is provided by a Peterson alkenation reaction. Finally, the intermediate vinylcarbene species may be intercepted by alkenes, to yield methylenecyclopropanes.2a,16

With aldehydes, treatment with dialkyl diazomethylphosphonate leads exclusively to terminal alkynes (eq 8).2b,6a This has proven useful, and is compatible with adjacent chirality (eqs 9 and 10).17,18 The method provides a useful alternative to the Corey-Fuchs protocol, which could prove troublesome in some circumstances.19

Cyclopropanation.

The reagents furnish cyclopropylphosphonates on exposure to alkenes in the presence of a metal or metal salt (eq 11).1,20

Cycloadditions.

The dipolar nature of the reagent has been exploited in the synthesis of pyrazolines,1 1,2,4-diazaphospholes (eq 12),21 dihydropyridazines,18 pyridazines,22 and pyrazoles.23 On installation of a dipolarophilic group a to the diazo moiety, intramolecular cycloadditions are possible, and have been extensively investigated (eq 13).24

Related Reagents.

Methylenecyclopropane.


1. Seyferth, D.; Marmor, R. S.; Hilbert, P. JOC 1971, 36, 1379.
2. (a) Lewis, R. T.; Motherwell, W. B. T 1992, 48, 1465. (b) Ohira, S. SC 1989, 19, 561.
3. Regitz, M.; Weber, B.; Eckstein, U. LA 1979, 1002.
4. Disteldorf, W.; Regitz, M. CB 1976, 109, 546.
5. Holmquist, C. R.; Roskamp, E. J. TL 1992, 33, 1131.
6. (a) Gilbert, J. C.; Weerasooriya, U. JOC 1982, 47, 1837. (b) Gilbert, J. C.; Weerasooriya, U. JOC 1983, 48, 448.
7. Gilbert, J. C.; Weerasooriya, U. JOC 1979, 44, 4997.
8. For an exception, see: Gilbert, J. C.; Baze, M. E. JACS 1984, 106, 1885.
9. Gilbert, J. C.; Giamalva, D. H.; Weerasooriya, U. JOC 1983, 48, 5251.
10. Gilbert, J. C.; Weerasooriya, U.; Wiechman, B.; Ho, L. TL 1980, 21, 5003.
11. Gilbert, J. C.; Senaratne, K. P. A. TL 1984, 25, 2303.
12. (a) Ohira, S.; Ishi, S.; Shinohara, K.; Nozaki, H. TL 1990, 31, 1039. (b) Ohira, S.; Okai, K.; Moritani, T. CC 1992, 721.
13. Stewart, A. O.; Williams, R. M. Carbohydr. Res. 1984, 135, 167.
14. Buxton, S. R.; Holm, K. H.; Skattebøl, L. TL 1987, 28, 2167.
15. (a) Hauske, J. R.; Guadliana, M.; Desai, K. JOC 1982, 47, 5019. (b) Gilbert, J. C.; Blackburn, B. K. TL 1984, 25, 4067. (c) Gilbert, J. C.; Blackburn, B. K. JOC 1986, 51, 4087.
16. Gilbert, J. C.; Weerasooriya, U.; Giamalva, D. TL 1979, 4619.
17. (a) Hauske, J. R.; Dorff, P.; Julin, S.; Martinelli, G.; Bussolari, J. TL 1992, 33, 3715. (b) Parry, R. J.; Muscate, A.; Askonas, L. J. B 1991, 30, 9988. (c) Nerenberg, J. B.; Hung, D. T.; Somers, P. K.; Schreiber, S. L. JACS 1993, 115, 12 621.
18. Delpech, B.; Lett, R. TL 1989, 30, 1521.
19. Yau, E. K.; Coward, J. K. JOC 1990, 55, 3147.
20. (a) Seyferth, D.; Marmor, R. S. TL 1970, 2493. (b) Lewis, R. T.; Motherwell, W. B. TL 1988, 29, 5033.
21. Märkl, G.; Trötsch, I. AG(E) 1984, 23, 901.
22. Heydt, H.; Eisenbarth, P.; Feith, K.; Regitz, M. JHC 1986, 23, 385.
23. Regitz, M.; Martin, R. PS 1983, 18, 163.
24. Regitz, M.; Schoder, W. S 1985, 178.

Kevin M. Short

Wayne State University, Detroit, MI, USA

Christopher J. Moody

Loughborough University of Technology, UK



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