Diethyl Difluoromethylphosphonate

[1478-53-1]  · C5H11F2O3P  · Diethyl Difluoromethylphosphonate  · (MW 188.11)

(precursor for the introduction of (EtO)2P(O)CF2- and =CF2 groups into organic compounds)

Preparative Methods: prepared by the reaction of sodium diethyl phosphite with Chlorodifluoromethane in hexane (49% yield)1 or in THF (77% yield);2 or generated in situ from diethyl bromodifluoromethylphosphonate and BuLi.3

Reaction with Carbonyl Compounds.

Deprotonation of diethyl difluoromethylphosphonate with Lithium Diisopropylamide at -78 °C gives the carbanion (eq 1) which is only stable at or below -78 °C.2 Reaction of the carbanion with aldehydes and ketones at -78 °C, followed by decomposition (heating THF solution) of the intermediate, gives the corresponding 1,1-difluoroalkenes (eq 2).2,4 The intermediate can be trapped by electrophiles, such as proton2,5 and acid chlorides,6 to form the corresponding phosphonates.

Reaction with Alkyl and Allyl Halides and Alkyl Triflates.

The carbanion of diethyl difluoromethylphosphonate also reacts with alkyl halides,2,7,8 alkyl triflates,9 oxalate,10 and allyl bromide2 to form the corresponding 1,1-difluoro phosphonates (eq 3).

Reaction with Other Electrophiles.

The carbanion of diethyl difluoromethylphosphonate can be trapped with Chlorotrimethylsilane or trialkylchlorostannanes to produce the corresponding trimethylsilylated and trialkyltin-substituted 1,1-difluoro phosphonates (eq 4).2

The carbanion also reacts with diethyl chlorophosphate or benzoyl chloride to give the corresponding a,a-difluoro bisphosphonate and b-ketophosphonate, respectively (eq 5).2,11,12 Treatment of the carbanion of diethyl difluoromethylphosphonate with Carbon Dioxide at -78 °C leads to the formation of the carboxylic acid (eq 6). The thiocarboxylic acid is formed by a similar reaction of the carbanion with Carbon Oxysulfide (eq 6).13 The carbanion reacts in a 1,4 addition with 4-chloro-b-nitrostyrene to give the nitro phosphonate (eq 7).14

1. (a) Soborovskii, L. Z.; Baina, N. F. JGU 1959, 29, 1115. (b) Bergstrom, D. E.; Shum, P. W. JOC 1988, 53, 3953.
2. Obayashi, M.; Ito, E.; Matsui, K.; Kondo, K. TL 1982, 23, 2323.
3. Sprague, L. G. Ph.D. Thesis, University of Iowa, 1986.
4. (a) Burton, D. J.; Yang, Z.-Y. T 1992, 48, 189. (b) Sagami Chemical Research Center Jpn. Patent 57 142 926 (CA 1983, 98, 34 296).
5. Halazy, S.; Gross-Berges, V. CC 1992, 743.
6. Martin, S. F.; Dean, D. W.; Wagman, A. S. TL 1992, 33, 1839.
7. (a) Halazy, S; Ehrhard, A.; Danzin, C. JACS 1991, 113, 315. (b) Bigge, C. F.; Drummond, J. T.; Johnson, G. TL 1989, 30, 7013.
8. Kim, C. U.; Luh, B. Y.; Misco, P. F.; Bronson, J. J.; Hitchcock, M. J. M.; Ghazzouli, I.; Martin, J. C. JMC 1990, 33, 1207.
9. Wolff-Kugel, D.; Halazy, S. TL 1991, 32, 6341.
10. Phillion, D. P.; Cleary, D. G. JOC 1992, 57, 2763.
11. Biller, S. A.; Forster, C.; Gordon, E. M.; Harrity, T.; Scott, W. A.; Ciosek, C. P., Jr. JMC 1988, 31, 1869.
12. Biller, S. A.; Forster, C. T 1990, 46, 6645.
13. Blackburn, G. M.; Brown, D.; Martin, S. J. JCR(S) 1985, 92.
14. Howson, W.; Hills, J. M.; Blackburn, G. M.; Broekman, M. BML 1991, 1, 501.

Donald J. Burton & Weiming Qiu

University of Iowa, Iowa City, IA, USA

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