Diethyl Diazomethylphosphonate1

(R = Et)

[25411-73-8]  · C5H11N2O3P  · Diethyl Diazomethylphosphonate  · (MW 178.13) (R = Me)

[27491-70-9]  · C3H7N2O3P  · Dimethyl Diazomethylphosphonate  · (MW 152.09)

(nucleophilic diazo species for the preparation of substituted diazophosphonates,3,4 b-ketophosphonates,5 alkynes,6-8 electron-rich alkenes,9 various cyclopropane derivatives,10-12 and five-membered rings13,14)

Alternate Name: DAMP.

Physical Data: yellow liquid, bp 51 °C/0.1 mmHg; 86-88 °C/0.2 mmHg.

Solubility: sol organic solvents.

Preparative Method: by diazotization of diethyl or dimethyl (aminomethyl)phosphonate using Sodium Nitrite under acidic conditions.2

Handling, Storage, and Precautions: should be stored under an inert atmosphere at 4 °C, and handled as any other diazo compound; all distillations should be carried out behind a blast shield.

Introduction.

The corresponding dimethyl ester, dimethyl diazomethylphosphonate, is also widely used; this entry discusses both reagents. The acronym DAMP is used for both the ethyl and methyl derivatives.

Preparation of Diazophosphonates.

Diethyl diazomethylphosphonate is readily lithiated (n-Butyllithium, THF, -100 °C) and the resulting lithio derivative can be acylated (Phenacyl Bromide, 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-hydroxyphosphonates result when the lithio derivative is treated with aryl aldehydes; alternatively, these can be prepared by direct reaction of DAMP with aldehydes in the presence of Triethylamine (eq 2).4

Preparation of b-Ketophosphonates.

In the presence of Tin(II) Chloride, DAMP adds to aldehydes to give b-ketophosphonates in reasonable yield (eq 3).5

Preparation of Alkynes.

Diaryl ketones are converted into alkynes by reaction of the lithium (or potassium) salt of DAMP. The reaction presumably involves a Horner-Wadsworth-Emmons-like elimination to give the diazoalkene, followed by aryl migration with loss of nitrogen (eq 4)6 (see also Diazo(trimethylsilyl)methyllithium).

Aldehydes react to give the homologous terminal alkyne by a similar mechanism involving hydrogen migration. The reaction appears to be quite general and has been applied to complex aldehydes for natural product synthesis (eqs 5 and 6).7,8

Preparation of Electron-Rich Alkenes.

Both acyclic and cyclic ketones are homologated to enol ethers or enamines by reaction with DAMP/Potassium t-Butoxide followed by an alcohol or secondary amine (eqs 7 and 8).9 The reaction presumably involves a diazoalkene intermediate, but, because alkyl groups migrate poorly, an alkyne is not formed; instead, reaction with the nucleophile occurs.

Preparation of Cyclopropanes.

When the above reactions of ketones are carried out in the presence of alkenes, alkylidenecyclopropanes are formed in good yield by addition to the alkylidenecarbene (eq 9).10

The reaction has been extended to a-phenylseleno ketones; in this case the resulting phenylseleno-substituted alkylidenecyclopropanes undergo rearrangement to vinylcyclopropanes.2c,11

An alternative route to alkylidenecyclopropanes involves Copper powder or Copper(I) Trifluoromethanesulfonate catalyzed reaction of the alkene with DAMP to give cyclopropylphosphonates, followed by Horner-Wadsworth-Emmons reaction with an aldehyde or ketone (eq 10).2a,12

Preparation of Five-Membered Rings.

The alkylidenecarbenes generated from diazoalkenes (resulting from reaction of ketones with DAMP) undergo intramolecular C-H insertion reactions to give cyclopentenes (eq 11)13 and dihydrofurans, and hence furans (eq 12).14


1. For general reviews, see: (a) Regitz, M. AG(E) 1975, 14, 222. (b) Regitz, M.; Maas, G. Diazo Compounds. Properties and Synthesis; Academic: Orlando, 1986.
2. (a) Seyferth, D.; Marmor, R. S.; Hilbert, P. JOC 1971, 36, 1379. (b) Regitz, M.; Liedhegener, A.; Eckstein, U.; Martin, M.; Anschütz, W. LA 1971, 748, 207. (c) Lewis, R. T.; Motherwell, W. B. T 1992, 48, 1465.
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. Colvin, E. W.; Hamill, B. J. JCS(P1) 1977, 869.
7. Nakatsuka, M.; Ragan, J. A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber, S. L. JACS 1990, 112, 5583.
8. Kabat, M.; Kiegiel, J.; Cohen, N.; Toth, K.; Wovkulich, P. M.; Uskoković, M. R. TL 1991, 32, 2343.
9. (a) Gilbert, J. C.; Weerasooriya, U. TL 1980, 21, 2041. (b) Gilbert, J. C.; Weerasooriya, U. JOC 1983, 48, 448. (c) Gilbert, J. C.; Weerasooriya, U.; Wiechman, B.; Ho, L. TL 1980, 21, 5003. (d) Gilbert, J. C.; Senaratne, K. P. A. TL 1984, 25, 2303.
10. Gilbert, J. C.; Weerasooriya, U.; Giamalva, D. TL 1979, 4619.
11. Lewis, R. T.; Motherwell, W. B. CC 1988, 751.
12. Lewis, R. T.; Motherwell, W. B. TL 1988, 29, 5033.
13. Gilbert, J. C.; Giamalva, D. H.; Weerasooriya, U. JOC 1983, 48, 5251.
14. Buxton, S. R.; Holm, K. H.; Skattebøl, L. TL 1987, 28, 2167.

Christopher J. Moody

Loughborough University of Technology, UK



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