Ethyl Difluoroiodoacetate

(R = Et)

[7648-30-8]  · C4H5F2IO2  · Ethyl Difluoroiodoacetate  · (MW 249.94) (R = Me)

[109872-87-9]  · C3H3F2IO2  · Methyl Difluoroiodoacetate  · (MW 235.92)

(useful for introduction of a CF2CO2R group)

Physical Data: R = Et, bp 70-72 °C/70 mmHg;1 bp 72-74 °C/70 mmHg.2

Preparative Methods: prepared by the reaction of FSO2OCF2CO2Et with NaI (93%) (eq 1);2 oxidation of CF2ICH=CF2 followed by esterification with EtOH (overall, 21% (eq 2);3 by the addition of ICl to EtOCF = CF2 followed by hydrolysis (overall, 44%) (eq 3);1 and by the iodination of XZnCF2CO2Et generated from BrCF2CO2Et (available commercially) and Zn (58-73%) (eq 4).4

Handling, Storage, and Precautions: handle in a fume hood

Reformatsky Reaction.

Treatment of difluoroiodoacetates with Zinc and aldehydes or imines gives the corresponding b-hydroxy-a,a-difluoro esters (eq 5)5 and a,a-difluoro b lactams,6 respectively. Alternatively, BrCF2CO2Et could also be utilized as a precursor for this transformation.7 Difluoroiodoacetates are converted to the 2,2-difluoroketene silyl acetal by the reaction with Zn and Chlorotrimethylsilane. Subsequently, the silyl acetal reacts with a,b-unsaturated compounds to form the 1,4-addition product or a mixture of 1,4-addition and 1,2-addition products.8

Formation and Reactions of the CuCF2CO2R Reagent.

The copper reagent CuCF2CO2R is prepared by the reaction of difluoroiodoacetate and Copper. This copper reagent couples with a variety of halides including vinyl bromides and iodides, aryl and alkyl iodides, and allyl and benzyl bromides (eq 6).9

Radical Addition to Alkenes.

Addition of difluoroiodoacetates to alkenes has been initiated by Cu,4,10 peroxide, and metallo complexes11 to give the corresponding ester adduct, which could be reduced by Zinc/Nickel(II) Chloride4 to form the iodine-free a,a-difluoro ester (eq 7). More conveniently, the a,a-difluoro ester could be prepared from difluoroiodoacetates and alkenes in the presence of Zn/NiCl2.6H2O.12 In this process, Zn/NiCl2.6H2O behaves both as the radical initiator and the reducing reagent (eqs 7 and 8).

Related Reagents.

Chlorodifluoromethane; Dibromodifluoromethane; Ethyl Bromozincacetate; Methyl Bromoacetate; Sodium Chlorodifluoroacetate; Zinc.

1. (a) Dyatkin, B. L.; Lantseva, L. T.; Knunyants, I. L. USSR Patent 289 081, 1971 (CA 1971, 74, 111 582). (b) Syntheses of Fluoroorganic Compounds; Knunyants, I. L.; Yakobson, G. G., Eds.; Springer: Berlin, 1985; p 63.
2. Knunyants, I. L.; Mukhametshin, F. M.; German, L. S.; Delyagina, N. I.; Korovushkin, G. G. IZV 1985, 1314 (Engl. transl.).
3. Grindahl, G. A.; Bajzer, W. X. Pierce, O. R. JOC 1967, 32, 603.
4. Yang, Z.-Y.; Burton, D. J. JOC 1991, 56, 5125.
5. Kitagawa, O.; Taguchi, T.; Kobayashi, Y. TL 1988, 29, 1803.
6. Taguchi, T.; Kitagawa, O.; Suda, Y.; Ohkawa, S.; Hashimoto, A.; Iitaka, Y.; Kobayashi, Y. TL 1988, 29, 5291.
7. For recent review see: Burton, D. J.; Yang, Z.-Y. T 1992, 48, 189.
8. Kitagawa, O.; Hashimoto, A.; Kobayashi, Y.; Taguchi, T. CL 1990, 1307.
9. (a) Taguchi, T.; Kitagawa, O.; Morikawa, T.; Nishiwaki, T.; Uehara, H.; Endo, H.; Kobayashi, Y. TL 1986, 27, 6103. (b) Kitagawa, O.; Taguchi, T.; Kobayashi, Y. CL 1989, 389.
10. Kitagawa, O.; Miura, A.; Kobayashi, Y.; Taguchi, T. CL 1990, 1011.
11. Kiseleva, L. N.; Dostovalova, V. I.; Velichko, F. K.; Cherstkov, V. F.; Sterlin, S. R.; Savicheva, G. I.; Kurykin, M. A.; German, L. C. IZV 1988, 1914 (Engl. transl.).
12. (a) Yang, Z.-Y.; Burton, D. J. CC 1992, 233. (b) Yang, Z.-Y.; Burton, D. J. JOC 1992, 57, 5144.

Donald J. Burton & Weiming Qiu

University of Iowa, Iowa City, IA, USA

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