Facile synthesis of fluorinated phosphonates via photochemical and thermal reactions

Article abstract of DOI:10.1021/ja971345t

Under UV irradiation (254 nm) at ambient temperature, a degassed mixture of (EtO)₂POP(OEt)₂ and R(f)I {(f) = CF₃, C2F₅, C₄F₉, C₆F₁₃, (CF₃)₂CF, CF₂CF=CF₂, ClCF₂CF₂, BrCF₂CF₂, C₆F₅, ClCF₂CFClCF₂CF₂, I(CF₂)₃, I(CF₂)₄. FO₂S(CF₂)₄, FO₂S(CF₂)₂O(CF₂)₂} affords the fluorinated phosphonite, [R(f)P(OEt)₂]. Oxidation of the phosphonites, [R(f)P(OEt)₂], with Me₃COOH gave the corresponding fluorinated phosphonates, (EtO)₂P(O)R(f) (1-14), in 35-80% isolated yields. CF₃CCl₂I reacts with (EtO)₂POP(OEt)₂ at room temperature in the absence of UV irradiation to afford [CF₃CCl₂P(OEt)₂] which upon oxidation gave a 52% yield of CF₃CCl₂P(O)(OEt)₂ (15). The reaction of (EtO)₂POP(OEt)₂ and R(f)I (R(f) = ClCF₂CF₂, BrCF₂CF₂ C₂F₅) at 125 °C in the presence of Me₃COOCMe₃ and subsequent oxidation of the resultant phosphonites afforded phosphonates (2, 7, and 8) albeit in lower yields (49-62%) compared to those of the photochemical reaction (58-80%). (RO)₂P(O)CF₂CF₂I (R = Et, i-Pr) (16 and 17) was obtained (42-48%) when a degassed mixture of (RO)₃P and BrCF₂CF₂I was subjected to UV irradiation (254 nm) at ambient temperature via a unique photochemical transformation.

Full text of DOI:10.1021/ja971345t

J. Am. Chem. Soc. 1997, 119, 9137-9143
9137
Facile Synthesis of Fluorinated Phosphonates Via Photochemical
and Thermal Reactions
Haridasan K. Nair and Donald J. Burton*
Contribution from the Department of Chemistry, UniVersity of Iowa, Iowa City, Iowa 52242
ReceiVed April 28, 1997X
Abstract: Under UV irradiation (254 nm) at ambient temperature, a degassed mixture of (EtO)2POP(OEt)2 and RfI
{Rf ) CF3, C2F5, C4F9, C6F13, (CF3)2CF, CF2CFdCF2, ClCF2CF2, BrCF2CF2, C6F5, ClCF2CFClCF2CF2, I(CF2)3,
I(CF2)4, FO2S(CF2)4, FO2S(CF2)2O(CF2)2} affords the fluorinated phosphonite, [RfP(OEt)2]. Oxidation of the
phosphonites, [RfP(OEt)2], with Me3COOH gave the corresponding fluorinated phosphonates, (EtO)2P(O)Rf (1-
14), in 35-80% isolated yields. CF3CCl2I reacts with (EtO)2POP(OEt)2 at room tempearture in the absence of UV
irradiation to afford [CF3CCl2P(OEt)2] which upon oxidation gave a 52% yield of CF3CCl2P(O)(OEt)2 (15). The
reaction of (EtO)2POP(OEt)2 and RfI (Rf ) ClCF2CF2, BrCF2CF2, C2F5) at 125 °C in the presence of Me3COOCMe3
and subsequent oxidation of the resultant phosphonites afforded phosphonates (2, 7, and 8) albeit in lower yields
(49-62%) compared to those of the photochemical reaction (58-80%). (RO)2P(O)CF2CF2I (R ) Et, i-Pr) (16 and
17) was obtained (42-48%) when a degassed mixture of (RO)3P and BrCF2CF2I was subjected to UV irradiation
(254 nm) at ambient temperature Via a unique photochemical transformation.
Introduction
Soborovoskii and Baina prepared (EtO)2P(O)CF2H Via reac-
tion of the diethylphosphite anion with chlorodifluoromethane
(eq 1).2 Later, synthesis of dialkyl (bromodifluoromethyl)-
Phosphate esters constitute one of the most significant
structural entities in all living organisms, and the preparation
of a number of new phosphonates and their biochemical studies
have been reported.1 The first preparation of a fluorinated
phosphonate, (EtO)2P(O)CF2H, was reported by Soborovskii and
Baina 37 years ago.2 Since then, relatively few fluorinated
phosphonates have been reported, compared to their nonfluori-
nated analogues, although it is well documented that incorpora-
tion of fluorine into biologically important compounds results
in enhanced activity and stability while a steric demand similar
to the hydrogen atom is exhibited.3 This dearth of fluorinated
analogues can be attributed to the lack of synthetic procedures,
since methods commonly used for the preparation of phospho-
nates cannot usually be applied to fluorinated analogues.
phosphonate, from a trialkylphosphite and CF2Br2, was reported
(eq 2).16 Although, mechanistically, both of these reactions (eqs
(4) (a) Chambers, R. D.; O’Hagan, D.; Lamont, B. R.; Jain, S. C. J.
Chem. Soc., Chem. Commun. 1990, 1053. (b) Chambers, R. D.; Jaouhari,
R.; O’Hagan, D. J. Fluorine Chem. 1989, 44, 275. (c) Arabshahi, L.; Khan,
N. N.; Butler, M.; Noonan, T.; Brown, N. C.; Wright, G. E. Biochemistry
1990, 29, 6820. (d) Stremler, K. E.; Poulter, C. D. J. Am. Chem. Soc. 1987,
109, 5542. (e) Davisson, V. J.; Woodside, A. B.; Neal, T. R.; Stremler, K.
E.; Muehlbacher; Poulter, C. D. J. Org. Chem. 1986, 51, 4768. (f) Vrang,
L.; Oeberg, B. Antimicrob. Agents Chemother. 1986, 29, 867-872. (g)
Blackburn, G. M.; Rashid, A.; Bisbal, C.; Lebleu, B. Chem. Scr. 1986, 26,
21. (h) Davisson, V. J.; Davis, D. R.; Dixit, V. M.; Poulter, C. D. J. Org.
Chem. 1987, 52, 1794. (i) Bigge, C. F.; Drummond, J. T.; Johnson, G.
Tetrahedron Lett. 1989, 30, 7013. (j) Burton, D. J.; Sprague, L. G. J. Org.
Chem. 1989, 54, 613. (k) Su, D.; Cen, W.; Kirchmeir, R. L.; Shreeve, J.
M. Can. J. Chem. 1989, 67, 1795. (l) Chambers, R. D.; Jaouhari, R.;
O’Hagan, D. J. Chem. Soc., Chem. Commun. 1988, 1169. (m) Yang, Z.
Y.; Burton, D. J. Tetrahedron Lett. 1991, 32, 1019. (n) Differding, E.;
Duthaler, R. O.; Ruegg, G. M.; Schmit, C. Synth. Lett. 1991, 395. (o) Yang,
Z. Y.; Burton, D. J. J. Org. Chem. 1992, 57, 4676. (p) Hu, C. M.; Chen, J.
J. Chem. Soc., Perkin Trans. 1993, 1, 327. (q) Burton, D. J.; Yang, Z. Y.;
Qiu, W. Chem. ReV. 1996, 96, 1641
(5) (a) Berkowitz, D. B.; Eggen, M.; Shen, Q.; Shoemaker, R. K. J. Org.
Chem. 1996, 61, 4666. (b) Austin, R. E.; Cleary, D. G. Nucleosides
Nucleotides 1996, 14, 1803. (c) Herpin, T. F.; Houlton, J. S.; Motherwell,
W. B.; Roberts, B. P.; Wiebel, J. J. Chem. Soc., Chem. Commun. 1996,
613. (d) Piettre, S. R. Tetrahedron Lett. 1996, 37, 2233. (e) Nieschalk, J.;
Batsanov, A.; O’Hagan, D.; Howard, J. A. K. Tetrahedron 1996, 52, 165.
(f) Leqeux, T. P.; Percy, J. M. J. Chem. Soc., Chem. Commun. 1995, 2111.
(g) Nieschalk, J.; O’Hagan, D. J. Chem. Soc., Chem. Commun. 1995, 719.
(h) Otaka, A.; Miyoshi, K.; Burke, T. R., Jr.; Roller, P. P.; Kubota, H.
Tetrahedron Lett. 1995, 36, 927. (i) Matulic-Adamic, J.; Haeberli, P.;
Usman, N. J. Org. Chem. 1995, 60, 2563. (j) Berkowitz, D. B.; Shen, Q.;
Maeng, J. H. Tetrahedron Lett. 1994, 35, 6445. (k) Gordeev, M. F.; Patel,
D. V.; Barker, P. L.; Gordon, E. M. Tetrahedron Lett. 1994, 35, 7585. (l)
Smyth, M. S.; Burke, T. R., Jr; Tetrahedron Lett. 1994, 35, 551. (m) Vinod,
T. K.; Griffith, H.; Keana, J. F. W. Tetrahedron Lett. 1994, 35, 7193. (n)
Wrobel, J.; Dietrich, A. Tetrahedron Lett. 1993, 34, 3546. (o) Burke, T.
R., Jr.; Smyth, M. S.; Otaka, A.; Roller, P. P. Tetrahedron Lett. 1993, 34,
4125. (p) Berkowitz, D. B. J. Org. Chem. 1993, 58, 6174.
In recent years, the desirable properties conferred upon
fluorine substitution have caused an increased interest in the
study of fluorinated phosphonates.4,5 Blackburn and co-
workers6 suggested that (R,R-difluoroalkyl)phosphonates should
mimic phosphate esters better than the corresponding phospho-
nates. Therefore, fluorinated phosphonates have been investi-
gated as phosphonate analogues,4-6 enzyme inhibitors,7 fuel cell
electrolytes,8 and chelating agents.9 The continued interest in
these compounds is manifested by the recent syntheses of a
number of novel fluorinated bisphosphonates, bisphosphonic
acids,10-13 and phosphonic acids.14,15
X Abstract published in AdVance ACS Abstracts, September 1, 1997.
(1) Engel, R. Chem. ReV. 1977, 77, 349.
(2) Soborovoskii, L. Z.; Baina, N, N. F. Zh. Obshch. Khim. 1959, 29,
1144; J. Gen. Chem. USSR (Engl. Transl.) 1959, 29, 1115.
(3) (a) Filler, R., Kobayashi, Y., Yagupolskii, L. M., Eds.; Organofluorine
Compounds in Medicinal Chemistry and Biomedical Applications; Else-
vier: Amsterdam, New York, 1993. (b) Welch, J. T.; Eswarakrishnan, S.
Fluorine in Bioorganic Chemistry; John Wiley & Sons Inc.: New York,
1991. (c) Welch, J. T., Ed.; SelectiVe Fluorination in Organic and
Bioorganic Chemistry; ACS Symposium Series 456; American Chemical
Society Washington, DC, 1991. (d) Filler, R., Kobayashi, Y., Eds.;
Biomedical Aspects of Fluorine Chemistry; Kodasha/Elsevier: New York,
1982. (e) Welch, J. T. Tetrahedron 1987, 43, 3123. (f) Filler, R., Ed.;
Biochemistry InVolVing Carbon-Fluorine Bonds; ACS Symposium Series
28; American Chemical Society: Washington, DC, 1976.
S0002-7863(97)01345-0 CCC: $14.00 © 1997 American Chemical Society

9138 J. Am. Chem. Soc., Vol. 119, No. 39, 1997
Nair and Burton
Scheme 1
1 and 2) appear to be SN2 type displacements, they actually
involve the generation and subsequent capture of
difluorocarbene.17-20 Thus, the above methods are specific for
difluoromethyl analogues and cannot be extended to higher
homologues. Photochemical preparation of (EtO)2P(O)Rf {Rf
) CF3, C6F5} Via treatment of a mixture of (EtO)3P and CF3I
or C6F5I has been reported;21 however, this procedure was not
successful for the synthesis of higher homologues.17 In 1981,
Kato and Yamabe reported the synthesis of (EtO)2P(O)Rf (Rf
) C6F13, C4F9, (CF3)2CF) in 41-71% yield Via a thermally-
induced radical reaction of tetraethylpyrophosphite and the
respective F-alkyl iodide.22 Recently, the reaction of (EtO)2P-
(O)Cl and in situ generated RfMgX {Rf ) C6F13, Cl(CF2)4, Cl-
(CF2)6, Cl(CF2)8, and FO2S(CF2)2O(CF2)4} at -50 °C was
reported to afford the corresponding F-alkylphosphonates.23 In
a recent paper,24 we reported the preparation of dialkyl (â-
halotetrafluoroethyl)phosphonates Via thermally- and photo-
chemically-induced radical reactions.
Table 1. Preparation of Fluorinated Phosphonates
isolated yield
(%)b
no. method
product
(EtO)2P(O)CF3
(EtO)2P(O)C2F5
(EtO)2P(O)CF(CF3)2
(EtO)2P(O)C4F9
1
2
3
A
A, B
A
63
58, 49
63
4
A
69
79
59
5
6
7
8
A
A
A, B
A, B
A
(EtO)2P(O)C6F13
(EtO)2P(O)CF2CFdCF2
(EtO)2P(O)CF2CF2Br
(EtO)2P(O)CF2CF2Cl
(EtO)2P(O)(CF2)3I
As part of our program, we investigated the synthesis of
fluorinated phosphonates by various approaches. In this paper,
we describe the facile synthesis of a number of novel as well
as previously reported dialkyl fluorinated phosphonates from
readily available substrates, in good yields, Via photochemically-
and thermally-induced radical reactions.
80, 62
75, 53
37
9
10
11
12
13
14
15
16
17
A
A
A
A
A
C
D
D
(EtO)2P(O)(CF2)4I
(EtO)2P(O)C6F5
35
35
72
57
64
52
42
48
(EtO)2P(O)CF2CF2CFClCF2Cl
(EtO)2P(O)CF2CF2OCF2CF2SO2F
(EtO)2P(O)(CF2)4SO2F
(EtO)2P(O)CCl2CF3
(EtO)2P(O)CF2CF2I
(i-PrO)2P(O)CF2CF2I
Results and Discussion
Kato and Yamabe prepared RfP(O)(OEt)2 {Rf ) C6F13, C4F9,
and (CF3)2CF} in 41-71% yield Via thermally-induced radical
reaction by heating a mixture of (EtO)2POP(OEt)2 and the
appropriate RfI in the presence of di-tert-butyl peroxide in an
a Method A (EtO)2POP(OEt)2 + RfI, under UV irradiation (254 nm);
method B (EtO)2POP(OEt)2 + RfI + Me3COOCMe3, at 125-130 °C;
method C (EtO)2POP(OEt)2 + RfI, at room temperature in the absence
of UV irradiation (254 nm); method D (RO)3P + RfI (R ) Et or i-Pr),
under UV irradiation (254 nm). b All yields are based on the respective
fluorinated iodide.
(6) (a) Blackburn, G. M.; Kent, D. E.; Kolkman, F. J. Chem. Soc., Perkin
Trans. 1 1984, 1119. (b) Blackburn, G. M.; Eckstein, F.; Kent, D. E.; Perree,
T. D. Nucleosides Nucleotides 1985, 4, 165. (c) Blackburn, G. M.; Brown,
D.; Martin, S. J.; Paratt, M. J. J. Chem. Soc., Perkin Trans. 1 1987, 181.
(7) (a) Halazy, S.; Ehrhard, A.; Eggenspiller, A.; Berges-Gross, V.;
Danzin, C. Tetrahedron 1996, 52, 177. (b) Halazy, S.; Ehrhard, A.; Danzin,
C. J. Am. Chem. Soc. 1991, 113, 315. (c) Martin, S. F.; Wong, Y.; Wagman,
A. S. J. Org. Chem. 1994, 59, 4821. (d) Burke, T. R., Jr.; Kole, H. K.;
Roller, P. P. Biochem. Biophys. Res. Commun. 1994, 204, 129. (e) Phillion,
D. P.; Cleary, D. G. J. Org. Chem. 1992, 57, 2763. (f) Chambers, R. D.;
Jaouhari, R.; O’Hagan, D. Tetrahedron 1989, 45, 5101.
(8) Mahmood, T.; Shreeve, J. M. Inorg. Chem. 1986, 25, 3128.
(9) (a) Fonong, T.; Burton, D. J.; Pietryzk, D. J. Anal. Chem. 1983, 55,
1089. (b) Frank, A. W. J. Org. Chem. 1965, 30, 3663.
(10) (a) Burton, D. J.; Pietryzk, D. J.; Ishihara, T.; Flynn, R. M. J.
Fluorine Chem. 1982, 20, 617. (b) Burton, D. J. US Pat. 4330 486, May
1982. (c) McKenna, C. E.; Shen, P. J. Org. Chem. 1981, 46, 4573. (d)
McKenna, C. E. U. S. Pat. 4478 763, 23, October 1984.
(11) Nair, H. K.; Guneratne, R. D.; Modak, A. S.; Burton, D. J. J. Org.
Chem. 1994, 59, 2393.
(12) Nair, H. K.; Burton, D. J. Tetrahedron Lett. 1995, 36, 347.
(13) (a) Burton, D. J.; Sprague, L. G.; Pietrzyk, D. J.; Edelmuth, S. H.
J. Org. Chem. 1984, 49, 3437. (b) Burton, D. J.; Sprague, L. G. J. Org.
Chem. 1988, 53, 1523. (c) Blackburn, G. M.; Brown, D.; Martin, S. J. J.
Chem. Res. S 1985, 92.
(14) Burton, D. J.; Modak, A. S.; Guneratne, R.; Su, D.; Cen, W.;
Kirchmeier, R. L.; Shreeve, J. M. J. Am. Chem. Soc. 1989, 111, 1773.
(15) (a) Sprague, L. G.; Burton, D. J.; Guneratne, R. D.; Bennett, W.
M. J. Fluorine Chem. 1990, 49, 75. (b) Su, D.; Guo, Y. C.; Willet, R. D.;
Scott, B.; Kirchmeier, R. L.; Shreeve, J. M. J. Am. Chem. Soc. 1990, 112,
3152.
(16) Burton, D. J.; Flynn, R. M. J. Fluorine Chem. 1977, 10, 329.
(17) Flynn, R. M. Ph.D. Thesis, University of Iowa, 1979.
(18) Burton, D. J. J. Fluorine Chem. 1983, 23, 339.
autoclave.22 However, the preparation of a functionalized
phosphonate, for example, a dialkyl (â-halo or ω-halofluoro-
alkyl)phosphonate, has not been demonstrated by this procedure.
We sought a milder procedure which avoids heating the reaction
mixture with a peroxide at high temperature and which could
be utilized for the synthesis of F-alkyl as well as functionalized
F-alkyl phosphonates. We report a convenient photochemical
method that meets both criteria, as discussed below.
Under UV irradiation (254 nm) at ambient temperature, a
degassed mixture of (EtO)2POP(OEt)2 and a fluorinated iodide
afforded the corresponding phosphonite, [(EtO)2PRf]. A number
of fluorinated iodides, primary, secondary, aromatic, allyl,
â-halo, ω-halo, R,ω-dihalo, and substituted F-alkyl, could be
employed (Scheme 1). Although the phosphonites were not
isolated, they could be characterized by 31P{1H} NMR analysis,
since the difference in chemical shifts between the phosphonite
and phosphonate is typically more than 130 ppm.24,25 Oxidation
of the in situ generated phosphonites with Me3COOH in
methanol at -20 °C afforded the corresponding phosphonates
(Scheme 1). By this method, the new phosphonates (2, 7-10
and 12-14), as well as previously reported phosphonates, (1,
3-6, and 11), were obtained in 35-80% yields (Table 1).
Purification of the phosphonates was best accomplished by frac-
(19) Haszeldine, R. N.; West, B. O. J. Chem. Soc. 1956, 3631.
(20) Teichman, H. Z. Chem. 1974, 14, 216.
(21) Burton, D. J.; Flynn, R. M. Synthesis 1979, 615.
(22) Kato, M.; Yamabe, M. J. Chem. Soc., Chem. Commun. 1981, 1173.
(23) Cen, W.; Shen, Y. J. Fluorine Chem. 1991, 52, 369.
(24) Nair, H. K.; Burton, D. J. J. Am. Chem. Soc. 1994, 116, 6041.
(25) For example, the proton-decoupled 31P NMR δ values for [(EtO)2-
PCF2CF2Cl] and (EtO)2P(O)CF2CF2Cl are 144.8 (tt) and 0.23 (tt) ppm,
respectively; similarly, 31P{1H} NMR δ values for [(EtO)2PC6F13] and
(EtO)2P(O)C6F13 are 144.5 and 0.81 ppm, respectively.

Facile Synthesis of Fluorinated Phosphonates
J. Am. Chem. Soc., Vol. 119, No. 39, 1997 9139
Scheme 2
Scheme 3
tional distillation or column chromatography; the latter always
gave better yields, since some decomposition occurs in the
former case. This interesting photochemical conversion can be
conveniently carried out in a quartz vessel at 254 nm; at 300
nm a slight decrease (∼5%) in the yields of the phosphonates
was observed.
CCl2I was so reactive that it reacted even at room temperature
without UV irradiation.
The photochemical procedure can also be extended to the
preparation of bisphosphonates.24 For example, the reaction of
(EtO)2P(O)CF2I and (EtO)2POP(OEt)2 under UV resulted in the
corresponding mixed PIII and PV intermediate [(EtO)2P(O)CF2P-
(OEt)2], which affords the bisphosphonate, (EtO)2P(O)CF2P-
(O)(OEt)2 upon oxidation (eqs 3 and 4). The PIII-PV interme-
When a degassed mixture of (EtO)2POP(OEt)2, C6F13I, and
1-heptene (1.2:1:1) was irradiated (254 nm), 19F and 31P{1H}
NMR analyses of the reaction mixture revealed the formation
of the adduct, CH3(CH2)4CHICH2C6F13; no [(EtO)2PC6F13] was
detected. On the other hand, heating a degassed mixture of
(EtO)2POP(OEt)2 and C6F13I (1.2:1) to 100-110 °C for 9 h
did not afford any detectable amount of [(EtO)2PC6F13]. A
possible mechanism for the photochemical transformation is
illustrated in Scheme 2. The photolytic cleavage of RfI affords
Rf• and I•, in the initiation step. Subsequent reaction of Rf• and
(EtO)2POP(OEt)2 results in (EtO)2PRf and (EtO)2P(O)•;
(EtO)2P(O)• abstracts an iodine atom from the perfluoroalkyl
iodide generating Rf• which continues the chain process.
The photochemically-induced radical reaction can also be
extended to the preparation of ω-iodo-F-alkylphosphonates,
(EtO)2P(O)(CF2)3I and (EtO)2P(O)(CF2)4I, by irradiation (4 h)
of a mixture of the diiodide, I(CF2)nI (n ) 3, 4), and
tetraethylpyrophosphite in a 1 to 1.2 ratio, followed by oxidation.
Requisite 1,3-diiodoperfluoropropane was prepared, in 68%
yield, from perfluoroglutaryl chloride Via a reported procedure.26
The yields of the ω-iodophosphonates were generally low since
the product iodophosphonites react further to form the bisphos-
phonites;12 the best isolated yields of 9 and 10 were 37 and
35%, respectively. In addition, small amounts (5-10%) of
(EtO)2P(O)(CF2)nH were also observed. If excess tetraethylpy-
rophosphite is employed, the exclusive formation of bisphos-
phonites could be effected in good yield.12
Reaction of a degassed mixture of ICF2CF2I and tetraeth-
ylpyrophosphite under photochemical conditions afforded only
F2CdCF2; formation of [(EtO)2PCF2CF2I] was not observed by
31P and 19F NMR analyses. However, UV irradiation of a
mixture of XCF2CF2I (X ) Cl, Br) and (EtO)2POP(OEt)2 and
subsequent oxidation of the resultant phosphonite with Me3-
COOH furnished (EtO)2P(O)CF2CF2Cl (8) and (EtO)2P(O)CF2-
CF2Br (7) in 75 and 80%, respectively.24 When a degassed
mixture of F2CdCFI and (EtO)2POP(OEt)2 was subjected to
UV irradiation, no vinylphosphonite was detected by 19F NMR
analysis. However, reaction of F2CdCFCF2I and tetraethylpy-
rophosphite under UV irradiation resulted in F-allylphosphonite,
which upon subsequent oxidation afforded the corresponding
phosphonate (6) in 59% yield. Similarly, substituted F-alkyl
iodides ClCF2CFClCF2CF2I, ICF2CF2OCF2CF2SO2F, and I(CF2)4-
SO2F reacted readily with (EtO)2POP(OEt)2 to afford the
respective phosphonites. After oxidation with Me3COOH, the
phosphonates 12-14 were obtained in 57-72% yield. CF3-
diate can easily be identified in the 31P NMR spectrum, since
the chemical shifts of the two P atoms differ by more than 130
ppm. Similarly, the irradiation of I(CF2)nI (n ) 3, 4, 6) and
(EtO)2POP(OEt)2 resulted in the corresponding bisphosphonites,
[(EtO)2P(CF2)nP(OEt)2], which on oxidation afforded the re-
24
spective bisphosphonates, (EtO)2P(O)(CF2)nP(O)(OEt)2. Thus,
the photochemical reaction is a general and versatile procedure
that can be employed for the preparation of a variety of
fluorinated phosphonates and bisphosphonates.
We were interested in extending the Kato-Yamabe reaction22
for the preparation of â- and ω-halo-F-alkylphosphonates. Thus,
when a degassed mixture of ICF2CF2I and (EtO)2POP(OEt)2
was heated at 125 °C in the presence of Me3COOCMe3, only
the formation of CF2dCF2 was observed by 19F NMR analysis
of the reaction mixture. On the other hand, BrCF2CF2Br was
found to be unreactive under the same conditions. In contrast,
when ICF2CF2X (X ) Br or Cl) was employed, (EtO)2P(O)CF2-
CF2Br (7) or (EtO)2P(O)CF2CF2Cl (8) could be obtained in 62
and 53% yields, respectively.24 Similarly, (EtO)2P(O)CF2CF3
(2) could also be prepared (49%) from CF3CF2I and (EtO)2-
POP(OEt)2. As noted in Table 1, the photochemical procedure
afforded 7, 8, and 2 in higher yields (80, 75, and 58%,
respectively) compared to the thermally-induced reaction. For
•
ICF2CF2I, loss of iodine radical from ICF2CF2 to afford
F2CdCF2 is faster than the capture of this radical by pyrophos-
phite. A possible mechanism is outlined in Scheme 3.22 The
reaction proceeds Via thermally-generated t-BuO•, which in turn
furnishes Rf•. Subsequent reaction of Rf• with tetraethylpyro-
phosphite affords the corresponding phosphonite and phosphoryl
radical, as depicted in Scheme 3.
Since, diethyl (2-iodotetrafluoroethyl)phosphonate, (EtO)2P-
(O)CF2CF2I, could not be obtained either by thermal or
photochemical reaction of (EtO)2POP(OEt)2 and ICF2CF2I, we
(26) (a) Krespan, C. G. J. Org. Chem. 1958, 23, 2016. (b) Patterson, W.
J.; Morris, D. E. US Pat. 3,763,204, 1973.

9140 J. Am. Chem. Soc., Vol. 119, No. 39, 1997
Nair and Burton
•
Scheme 4
ethane to afford (RO)2P(O)CF2CF2I and BrCF2CF2 ; the latter
continues the chain process.
One might ask why ICF2CF2I does not react with (EtO)3P to
give (EtO)2P(O)CF2CF2I? Since the rates of different steps in
the proposed mechnism (Scheme 4) are not known at present,
one cannot answer the above question with certainty. However,
it is possible that for ICF2CF2I, the dissociation of ICF2CF2• or
ICF2CF2- (to F2CdCF2 and I• or I-, respectively) is faster than
•
the dissociation of BrCF2CF2 or BrCF2CF2-. One would expect
the cleavage of the weaker C-I bond, compared to that of the
stronger C-Br bond, energetically to be more favorable, whether
induced photochemically or thermally. For example, when a
mixture of (EtO)2POP(OEt)2 and ICF2CF2I was heated under
degassed conditions, quantitative formation of F2CdCF2 was
observed. For BrCF2CF2I, generation of F2CdCF2 appears to
be slow compared to that of ICF2CF2I, since we could detect
small amounts (2-5%) BrCF2CF2I still left in the reaction
mixture after irradiation for 3.5 h.24 Thus, the loss of I• from
ICF2CF2• is faster than the capture of this radical by pyrophos-
phite. Also, treatment of ICF2CF2I with either (EtO)2POP(OEt)2
or (RO)3P, under photochemical or thermal (100 °C) conditions,
investigated an alternative approach for its preparation.27 Thus,
when a degassed mixture of (RO)3P and ICF2CF2I was irradiated
(254 nm) at ambient temperature, only the formation of
F2CdCF2 was observed; the outcome was the same when the
reaction mixture was heated to 100 °C. The reaction of
(EtO)2PONa with XCF2CF2I (X ) Cl, Br) also resulted in
F2CdCF2 formation. However, when BrCF2CF2I was employed
instead of ICF2CF2I, (RO)2P(O)CF2CF2I [R ) Et or i-Pr] was
obtained in 42-48% yields (eq 5) with no detectable amount
of bromo derivative!24 The yield was optimum when the ratio
of (RO)3P to BrCF2CF2I was 2 to 1.
•
resulted in F2CdCF2 only. In any case, the ICF2CF2 generated,
under thermal or photochemical conditions, has “limited”
stability. Thus, for the last step in Scheme 4, no ICF2CF2I is
left for the abstraction of the I• atom by (EtO)2P(O)CF2CF2• if
it is formed at all. Alternatively, (RO)2P(O)•, in principle, can
add to F2CdCF2 to give (RO)2P(O)CF2CF2• (Scheme 4) which
in turn can add to more F2CdCF2 in a chain reaction (to give
a polymer) or can dimerize to (RO)2P(O)(CF2CF2)2(O)P(OR)2.
However, we were unable to detect the formation of these
species by 19F and 31P NMR spectral analyses of the reaction
mixture.
The 13C{1H} NMR spectrum of (RO)2P(O)CF2CF2X (R )
Et, i-Pr; X ) Cl, Br, I) for -CF2CF2X region for compounds 7,
8, 16, and 17 exhibited a triplet of doublets of triplets (tdt) for
the R-C atom attached to the phosphorus and a triplet of triplets
of doublets (ttd) for the â-C atom. For example, 13C{1H} NMR
spectrum of compound 16 exhibited a tdt at δ 111.3 ppm (1JC,F
Our proposed mechanism24 for this remarkable transformation
is illustrated in Scheme 4. Photoinduced electron transfer
between the phosphite and 1-bromo-2-iodotetrafluoroethane
produces the radical cation, I,28-30 and radical anion, II,
respectively. A second electron transfer to II affords the
unstable BrCF2CF2-, which eliminates Br- to generate F2CdCF2.
Phosphoryl radical results on dealkylation of I by either I- or
Br-. Subsequent addition of phosphoryl radical to the tetrafluo-
1
2
) 273 Hz, JP,C ) 201 Hz, JC,F ) 37 Hz) and a ttd at δ 97.3
ppm (1JC,F ) 317 Hz, 2JC,F ) 37 Hz, 2JP,C ) 14 Hz), for R- and
â-carbon atoms attached to the P atom, respectively. The
experimental and simulated32 13C{1H} NMR spectra for the
>P(O)CF2CF2I region for 16 are illustrated in Figure 1.
In summary, photochemical reaction of tetraethylpyrophos-
phite and fluorinated iodides followed by oxidation affords the
corresponding phosphonates, in good yields. A variety of
fluorinated iodides, F-alkyl, substituted F-alkyl, F-aryl, F-allyl,
â-halo-F-alkyl, ω-halo-F-alkyl, ω-fluorosulfonyl-F-alkyl, and
substituted F-alkyl, can be employed. Dialkyl (â-iodotetrafluo-
roethyl)phosphonates were obtained in moderate yields by the
reaction of trialkylphosphite and BrCF2CF2I under photochemi-
cal conditions. The procedures described in this paper represent
convenient and simple routes to some of the previously reported
as well as new fluorinated phosphonates. We anticipate that
these interesting phosphonates will serve as precursors for the
development of biologically important phosphonate-derived
compounds and fuel cell electrolytes.
•
roethylene31 results in the formation of (RO)2P(O)CF2CF2 ,
which, in the last step, abstracts an iodine atom from the starting
(27) Our first approach to the synthesis of dialkyl (â-halotetrafluoroethyl)
phosphonates utilized the organometallic reagent derived from (EtO)2P-
(O)CF2Br, as shown below. Although the target phosphonates could be
obtained, the yields were consistently low and multiple carbene insertions
to the Cu-C bond in the (EtO)2P(O)CF2Cu could not be avoided.
(28) Bakkas, S.; Julliard, M.; Chanon, M. Tetrahedron 1987, 43, 501.
(29) ESR studies on radical cations, (MeO)3P•+ and (MeO)2HP•+, have
been reported: (a) Hasegawa, A.; McConnachie, G. D. G.; Symons, M. C.
R. J. Chem. Soc., Faraday Trans. 1 1984, 80, 1005. (b) Janes, R.; Symons,
C. R. J. Chem. Soc., Faraday Trans. 1 1990, 86, 2173. Recently, the
formation of triethylphosphite radical cation under photochemical conditions
has been reported.30
Experimental Section
General. All boiling points are uncorrected. 19F, 1H, 31P{1H}, and
13C{1H} NMR spectra were recorded on a JEOL FX90Q or Bruker
AC-300 spectrometer. All chemical shifts are reported in parts per
million (ppm) downfield (positive) of the standard. 19F NMR spectra
(30) Yasuda, M.; Yamashita, T.; Shima, K. Bull. Chem. Soc. Jpn. 1990,
63, 938.
(31) Addition of radicals to F2CdCF2 is well-known: Haszeldine, R.
N. J. Chem. Soc. 1953, 3761.
(32) Spectral simulation programs were designed and written by Dr. W.
E. Bennett, University of Iowa.

Facile Synthesis of Fluorinated Phosphonates
J. Am. Chem. Soc., Vol. 119, No. 39, 1997 9141
(20:80) or EtOAc/hexanes (10:90)). Boiling points and spectral data
of the phosphonates are given below.
Diethyl (trifluoromethyl)phosphonate (1, (EtO)2P(O)CF3): yield
1.93 g, 63%; bp 50-52 °C/4 mm Hg (lit.21 65-67.5 °C (8 mm Hg));
2
19F NMR (CDCl3) -73.3 (d, JP,F ) 124 Hz); 31P{1H} NMR (CDCl3)
2
1
3
-2.59 (q, JP,F ) 124 Hz); H NMR (CDCl3) 1.42 (t, 6H, JH,H ) 7
Hz), 4.35 (m, 4H); GC/MS (70 eV) m/e (% rel intensity) 207 (M+
+
1, 0.2), 191 (0.8), 179 (8), 163 (11), 151 (27), 137 (36), 131 (3), 121
(7), 109 (98), 93 (39), 91 (36), 81 (100), 69 (14).
Diethyl (pentafluoroethyl)phosphonate (2, (EtO)2P(O)C2F5): yield
2.2 g, 58%; bp 58-60 °C (5-7 mm Hg); 19F NMR (CDCl3) -82.0 (s,
2
3F), -126.13 (d, 2F, JP,F ) 88 Hz); 31P{1H} NMR (CDCl3) 0.39 (t,
2JP,F ) 88 Hz); 1H NMR (CDCl3) 1.41 (t, 6H, 3JH,H ) 7 Hz), 4.35 (m,
4H); 13C{1H} NMR (CDCl3) 16.3 (d, 3JPOC,C ) 4 Hz), 66.2 (d, 2JPOC
)
7 Hz), 110.6 (qtd, overlaps), 118.5 (tdq, overlaps); GC/MS (70 eV)
m/e (% rel intensity) 257 (M+ + 1, 0.9), 241 (2), 213 (21), 201 (41),
181 (12), 137 (52), 109 (100), 93 (13), 91 (35), 81 (100), 69 (10), 65
(27); FT-IR 2987 (w), 1323 (w), 1219 (s), 1165 (m), 1123 (m), 1050
(m), 1026 (s) cm-1
.
Diethyl (perfluoroisopropyl)phosphonate (3, (EtO)2P(O)CF-
(CF3)2): yield 2.9 g, 63%; bp 65-67 °C (7 mm Hg) (lit.22 70-72 °C
(21 mm Hg)); 19F NMR (CDCl3) -72.4 (d, 6F, 3JF,F ) 10 Hz), -192.6
2
3
(d heptets, 1F, JP,F ) 71 Hz, JF,F ) 10 Hz); 31P{1H} NMR (CDCl3)
Figure 1. Part of the 13C{1H} NMR spectrum of (EtO)2P(O)CF2CF2I;
simulated (lower trace) and experimental (upper trace).
2
1
3
2.44 (d, JP,F ) 71 Hz); H NMR (CDCl3) 1.41 (t, 6H, JH,H ) 7 Hz),
4.37 (m, 4H); 13C{1H} NMR (CDCl3) 16.32 (d, 3JPOC,C ) 5 Hz), 66.41
1
are referenced against internal CFCl3, H and 13C{1H} NMR spectra
(d, 2JPO,C ) 7 Hz), 89.90 (ddh, 1JC,F ) 238 Hz, 1JP,C ) 160 Hz, 2JC,F
)
against internal tetramethylsialne, and 31P{1H} NMR against external
H3PO4. FT-IR spectra were recorded as CCl4 solutions. Mass spectra
were acquired from a VG ZAB mass spectrometer operating at 70 eV
in the electron impact (EI) mode. Elemental analyses were performed
by Schwarkopf laboratories, Woodside, NY, or Galbraith Laboratories,
Knoxville, TN.
1
2
34 Hz), 120.45 (qd, JC,F ) 287 Hz, JC,F ) 25 Hz); GC/MS (70 eV)
m/e (% rel intensity) 307 (M+ + 1, 2), 291 (1), 279 (26), 277 (10),
263 (16), 251 (70), 233 (15), 231 (18), 150 (5), 137 (75), 131 (45),
109 (100), 93 (38), 91 (39), 81 (85), 69 (15), 65 (43); FT-IR 2987 (w),
1300 (m), 1285 (m), 1267 (m), 1228 (s), 1166 (w), 1054 (m), 1026 (s)
cm-1
.
Materials. BrCF2CF2I, ClCF2CF2I, ICF2CF2I, BrCF2CF2Br, C6F5I,
C2F5I, (CF3)2CFI, C4F9I, and C6F13I were obtained from PCR Inc.;
ClCF2CFClCF2CF2I was obtained from Japan Halon. CF2dCFCF2I
was donated by Y. Tarumi (University of Iowa). I(CF2)3I,26 CF3CCl2I,33
and I(CF2)4SO2F34 were prepared by reported procedures. I(CF2)4I and
ICF2CF2OCF2CF2SO2F were obtained from the Shanghai Institute of
Organic Chemistry, China. (EtO)3P, (i-PrO)3P, (EtO)2POP(OEt)2,
Me3COOCMe3, and Me3COOH were purchased from Aldrich Chemical
Company (EtO)3P and (i-PrO)3P were distilled over Na prior to use.
CF2ClCFCl2 and DMF were distilled over P2O5 and CaH2, respectively.
Method A. Representative Procedure for the Preparation of
(EtO)2P(O)Rf Wia Photochemical Reaction of (EtO)2POP(OEt)2 and
RfI. I. RfP(O)(OEt)2 {Rf ) CF3, C2F5, (CF3)2CF, CF2CFdCF2,
C4F9, C6F13, ClCF2CF2, BrCF2CF2}. Into a quartz tube (∼20 mL
capacity) equipped with a Teflon valve was added (EtO)2POP(OEt)2
(5.80 g, 22 mmol) under a stream of N2, which was degassed Via two
freeze-pump-thaw cycles (liquid N2, ∼0.05 mm Hg), and RfI (15
mmol) (Rf ) CF3, C2F5) was condensed into the tube. The Teflon
valve was closed, and the tube was warmed to room temperature. [For
RfI (Rf ) (CF3)2CF, ClCF2CF2, BrCF2CF2, CF2CFdCF2, C4F9, C6F13),
the appropriate iodide was added Via syringe to the tetraethylpyro-
phosphite under N2 and the reaction mixture was degassed immediately].
The degassed reaction mixture was irradiated (254 nm, Rayonet
photochemical reactor) at ambient temperature for 6-8 h (with CF3I,
only 4.5 h). The resultant reaction mixture from the quartz tube was
transferred to a 100 mL flask equipped with a nitrogen-tee and magnetic
stirbar, 15 mL of DMF was added, the flask was cooled by a salt/ice
bath (-20 to -10 °C), and Me3COOH (45 mmol) in MeOH (25 mL)
was added dropwise to the stirred reaction mixture, under N2; after
complete addition, the reaction mixture was stirred for an additional
hour. The resultant reaction mixture was concentrated on a rotary
evaporator, the residue poured into water (∼150 mL), and the crude
phosphonate was separated as the lower layer, which was transferred
by a pipette to CH2Cl2 (100 mL); the water layer was extracted with
25 mL of CH2Cl2. The combined CH2Cl2 extracts (125 mL) were dried
(MgSO4) and concentrated. The pure product was obtained by
distillation or by column chromatography (silica gel, CH2Cl2/hexanes
Diethyl (perfluorobutyl)phosphonate (4, (EtO)2P(O)C4F9): yield
3.9 g, 69%; bp 64-65 °C (0.5 mm Hg) (lit.22 52-53 °C (7 mm Hg));
19F NMR (CDCl3) -81.5 (m, 3F), -121.9 (m, 2F), -122.6 (dt, 2F, 2JP,F
2
) 90 Hz), -126.4 (t, 2F); 31P{1H} NMR (CDCl3) 0.37 (t, JP,F ) 90
1
3
Hz); H NMR (CDCl3) 1.41 (t, 6H, JH,H ) 7 Hz), 4.37 (m, 4H); GC/
MS (70 eV) m/e (% relative intensity) 357 (M+ + 1, 0.7), 356 (M+,
0.1), 327 (10), 301 (43), 281 (9), 137 (65), 131 (10), 109 (100), 93
(15), 91 (27), 81 (56), 69 (10), 65 (16); FT-IR: 2987 (w), 1241 (s),
1210 (m), 1150 (m), 1123 (m), 1045 (m), 1024 (s) cm-1
.
Diethyl (perfluorohexyl)phosphonate (5, (EtO)2P(O)C6F13): yield
5.4 g, 79%; bp 68-70 °C (0.7 mm Hg) (lit.22 58-60 °C (1.5 mm Hg));
19F NMR (CDCl3) -81.4 (t, 3F, JF,F ) 10 Hz), -120.8 (brs, 2F), -122.3
(brs, 2F), -121.1 to -121.9 (overlaps, 8F), -126.6 (brs, 2F); 31P{1H}
2
1
NMR (CDCl3) 0.81 (t, JP,F ) 90 Hz); H NMR (CDCl3) 1.41 (t, 6H,
3JH,H ) 7 Hz), 4.37 (m, 4H); GC/MS (70 eV) m/e (% rel intensity) 456
(M+, 0.2), 430 (2), 402 (12), 381 (6), 231 (2), 181 (4), 137 (77), 109
(54), 93 (35), 91 (54), 81 (86), 69 (23), 65 (31); FT-IR 2987 (w), 1293
(m), 1241 (s), 1210 (m), 1149 (m), 1045 (w), 1024 (s) cm-1
.
Diethyl (pentafluorophenyl)phosphonate (11, (EtO)2P(O)C6F5):
yield 1.05 g, 35%; bp 66-67 °C (0.05 mm Hg) (lit.21 146-156 °C (8
mm Hg)); 19F, 31P{1H}, and 1H NMR and IR data same as those
reported;21 GC/MS (70 eV) m/e (% rel intensity) 304 (M+, 1), 289 (2),
277 (14), 259 (9), 257 (16), 256 (42), 249 (100), 241 (12), 231 (62),
184 (19), 176 (24), 168 (20), 167 (12), 137 (8), 93 (6), 81 (13), 67 (8),
65 (29).
Diethyl (perfluoroallyl)phosphonate (6, (EtO)2P(O)CF2CFdCF2):
yield 2.4 g, 59%; bp 45-46 °C (0.8 mm Hg) (lit.35 36-40 °C (0.03
mm Hg)); 19F NMR (CDCl3) -91 (m, 1F), -107.3 (m, 1F), -117.3
(dm, 2F), -187.7 (m, 1F); 31P{1H} NMR (CDCl3) 3.4 (tm, 2JP,F ) 98
1
3
Hz); H NMR (CDCl3) 1.41 (t, 6H, JH,H ) 7 Hz), 4.34 (m, 4H); GC/
MS (70 eV) m/e (% rel intensity) 269 (M+ + 1, 0.9), 240 (9), 225 (30,
212 (55), 193 (11), 173 (3), 137 (18), 131 (57), 109 (84), 91 (35), 81
(100), 69 (10), 65 (16); FT-IR 2978 (w), 1784 (m), 1346 (m), 1295
(s), 1176 (m), 1097 (m), 1047 (m), 1024 (s), 806 (m) cm-1
.
Diethyl (2-bromotetrafluoroethyl)phosphonate (7, (EtO)2P(O)-
CF2CF2Br): yield 3.8 g, 80%; bp 40-45 °C (0.3 mm Hg); 19F NMR
(CDCl3) -62.4 (m, 2F), -116.1 (dt, 2F, 2JP,F ) 93 Hz, 3JF,F ) 5 Hz);
31P{1H} NMR (CDCl3) -0.48 (tt, 2JP,F ) 93 Hz, 3JP,F ) 4 Hz; 1H NMR
(33) (a) Lang, R. W. HelV. Chim. Acta 1988, 71, 369. (b) Unpublished
work of J. MacNeil, University of Iowa.
(34) Qiu, W.; Burton, D. J. J. Fluorine Chem. 1993, 60, 93.
(35) Sprague, L. G. Ph.D. Thesis, University of Iowa, 1984, p 276.

9142 J. Am. Chem. Soc., Vol. 119, No. 39, 1997
Nair and Burton
(CDCl3) 1.41 (t, 6H), 4.40 (m, 4H), 3JH,H = JP,H ≈ 7 Hz; 13C{1H} NMR
Ventilated fume hood), and the contents were poured into 200 mL cold
water. The product, 1,3-diiodo-1,1,2,2,3,3-hexafluoropropane, was
separated in the lower layer which was taken up in 100 mL of Et2O,
washed with 50 mL of H2O, dried (MgSO4), and distilled at 125-132
°C to give 74.6 g (68% yield) of ICF2CF2CF2I; 19F NMR (CDCl3) -58.0
(t, 4F) and -105.2 (p, 2F) ppm, 3JF,F ) 5 Hz; GC/MS 404 (M+); GLPC
purity 100%.
III. RfP(O)(OEt)2 {Rf ) I(CF2)3, I(CF2)4}. Similarly, a degassed
mixture of diodide (12 mmol) and (EtO)2POP(OEt)2 (10 mmol) was
irradiated (254 nm) for 4 h, oxidized with Me3COOH (20 mmol) in
MeOH (15 mL), and worked up (as given in method A.I); phosphonates
were purified by column chromatography (silica gel, CH2Cl2/hexanes
(20:80) or EtOAc/hexanes (10:90)).
3
2
(CDCl3) 16.31 (d, JPOC,C ) 5Hz), 66.07 (d, JPOC ) 7 Hz), 111.52
(tdt, 1JC,F ) 276 Hz, 1JP,C ) 204 Hz, 2JC,F ) 37 Hz), 117.20 (ttd, 1JC,F
) 310 Hz, 2JC,F ) 36 Hz, 2JP,C ) 19 Hz); GC/MS m/e (% rel intensity)
319/317 (M+ + 1, 1), 303 (1), 289 (24), 273 (9), 263 (31), 243 (21),
209 (27), 193 (15), 181 (50), 137 (82), 109 (100), 91 (20), 81 (66), 65
(13); FT-IR 2987, 2935, 1444, 1395, 1373, 1292, 1228, 1165, 1125,
1081,1025, 985, 895, 821, 779, 769, 586, 552 cm-1. Anal. Calcd. for
C6H10O3PF4Br: C, 22.73; H, 3.18; P, 9.70; F, 23.97; Br, 25.21.
Found: C, 23.09; H, 3.29; P, 9.17; F, 24.49; Br, 25.27.
Diethyl (2-chlorotetrafluoroethyl)phosphonate (8, (EtO)2P(O)-
CF2CF2Cl): yield 3.1 g, 75%; bp 50-60 °C (0.8 mm Hg); 19F NMR
(CDCl3) -67.7 (m, 2F), -119.3 (dt, 2F, 2JP,F ) 90 Hz, 3JF,F ) 5 Hz);
31P{1H} NMR (CDCl3) 0.23 (tt, 2JP,F ) 91 Hz, 3JP,F ) 4 Hz); 1H NMR
Diethyl (3-iodohexafluoropropyl)phosphonate (9, (EtO)2P(O)-
3
3
(CDCl3) 1.41 (t, 6H, JH,H ≈ JP,H ) 7 Hz), 4.36 (m, 4H); 13C{1H}
CF2CF2CF2I): yield 1.53 g, 37%; bp 95-100 °C (0.5 mm Hg); 19F
3
2
NMR (CDCl3) -58.7 (m, 2F), -120.7 (d, 2F), -121.2 (dt, 2F, 2JP,F
)
NMR (CDCl3) 16.31 (d, JPOC,C ) 5 Hz), 66.02 (d, JPOC ) 7 Hz),
1
1
2
92 Hz, 4JF,F ) 15 Hz); 31P{1H} NMR (CDCl3) 0.32 (tt, 2JP,F ) 92 Hz,
3JP,F ) 5 Hz); 1H NMR (CDCl3) 1.42 (t, 3JH,H ) 7 Hz), 4.30 (m, 4H);
GC/MS m/e (% rel intensity) 415 (M+ + 1, 0.2), 399 (0.2), 385 (2),
359 (3), 341 (5), 259 (14), 231 (66), 211 (6), 177 (14), 137 (56), 109
(100), 93 (16), 91 (35), 81 (83), 69 (11), 65 (25); FT-IR 2987 (w),
1294 (m), 1185 (s), 1107 (s), 1050 (m), 1026 (vs) cm-1. Anal. Calcd.
for C7H10O3F6PI: C, 20.30; H, 2.43; F, 27.53; P, 7.48; I, 30.65.
Found: C, 20.00; H, 2.59; F, 27.39; P, 8.20; I, 29.10.
111.55 (tdt, JC,F ) 276 Hz, JP,C ) 206 Hz, JC,F ) 39 Hz), 123.18
(ttd, 1JC,F ) 298 Hz, 2JC,F ) 39 Hz, 2JP,C ) 21 Hz); GC/MS m/e (% rel
intensity) (no M+) 247 (1), 245 (6), 231 (2), 229 (6), 219 (6), 217
(18), 209 (4), 199 (9), 181 (24), 137 (80), 109 (100), 100 (17), 93
(18), 81 (92), 67 (13), 65 (29); FT-IR 2986, 2934, 1444, 1395, 1373,
1292, 1242, 1166, 1123, 1091, 1025, 985, 964, 922, 847, 836, 807,
796, 784, 776, 766, 756, 749, 741 cm-1. Anal. Calcd. for C6H10O3-
PF4Cl: C, 26.44; H, 3.70; P, 11.36; F, 27.88; Cl, 13.00. Found: C,
26.51; H, 3.65; P, 10.82; F, 27.77; Cl, 12.86.
Diethyl (4-iodooctafluorobutyl)phosphonate (10, (EtO)2P(O)-
CF2CF2CF2CF2I): yield 1.61 g, 35%; bp 68-70 °C (0.01 mm Hg);
19F NMR (CDCl3) -59.7 (m, 2F), -113.4 (m, 2F), -119.8 (m, 2F),
II. RfP(O)(OEt)2 {Rf ) (CF2)4SO2F, ClCF2CFClCF2CF2, CF2-
CF2OCF2CF2SO2F, C6F5}. A degassed mixture of (EtO)2POP(OEt)2
(15 mmol) and appropriate RfI (10 mmol) was irradiated (254 nm) at
ambient temperature (in the case of C6F5I, 300 nm) for 6-8 h. [For
the preparation of FSO2(CF2)4P(O)(OEt)2, a degassed mixture of
I(CF2)4SO2F (7.8 mmol) and (EtO)2POP(OEt)2 (12 mmol) was irradi-
ated for 6-8 h]. After of 10 mL of DMF was added to the reaction
mixture, oxidation {with Me3COOH (30 mmol) in MeOH (20 mL)}
and workup were performed the same way as outlined above (method
A.I). Phosphonates were isolated by distillation under reduced pressure.
Diethyl (3,4-dichloro-1,1,2,2,3,4,4-heptafluorobutyl)phosphonate
(12, (EtO)2P(O)CF2CF2CFClCF2Cl): yield 3.0 g, 72%; bp 55-57 °C
2
1
-122.1 (dt, 2F, JP,F ) 90 Hz); 31P{1H} NMR (CDCl3) -0.16 (t); H
3
NMR (CDCl3) 1.40 (t, 6H, JH,H ) 7 Hz), 4.35 (m, 4H); GC/MS m/e
(% rel intensity) 465 (M+ + 1, 0.2), 435 (0.3), 421 (0.2), 337 (0.2),
309 (2), 281 (12), 208 (3), 177 (5), 137 (74), 109 (100), 100 (14), 93
(20), 91 (36), 81 (88), 69 (15), 65 (31); FT-IR 2987 (w), 1289 (m),
1194 (vs), 1148 (m), 1131 (vs), 1120 (m), 1051 (m), 1025 (vs) cm-1
.
Method B. Thermally-Induced Radical Reactions. (EtO)2P(O)-
CF2CF2Br (7). (EtO)2POP(OEt)2 (11.61 g, 45 mmol), CFCl2CF2Cl
(40 mL), BrCF2CF2I (9.24g, 30 mmol), and Me3COOCMe3 (3.04 g,
20mmol) were introduced sequentially into a 400 mL capacity hard
glass Rotaflo tube equipped with Teflon stopcock and magnetic stir
bar, under nitrogen. The reaction mixture was degassed (∼0.005 mm
Hg) Via two freeze-pump-thaw (liquid N2) cycles and brought to room
temperature. The stirred reaction mixture was then heated (Caution!
the reaction should be carried out in a well-Ventilated fume-hood behind
a safety shield) slowly to 125-130 °C in an oil bath and maintained at
this temperature for 3.5 h, cooled to room temperature, and transferred
to a 250 mL flask placed in an ice/salt bath. To the resultant reaction
mixture, Me3COOH (8.10 g, 90 mmol) in MeOH (40 mL) was added
dropwise Via an addition funnel, over a period of 20 min with constant
magnetic stirring. After 1 h of stirring, the reaction mixture was
concentrated on a rotary evaporator, and the residue was extracted with
CHCl3 (200 mL) and washed successively with water (2 × 50 mL),
saturated NaHCO3 (5 mL), saturated NaHSO3 (5 mL), and brine (5
mL). The CHCl3 layer was separated, dried (MgSO4), and concentrated
on a rotary evaporator. The residue was chromatographed (silica gel
column, eluent CH2Cl2/hexanes (15:85)). The crude phosphonate was
distilled Via a short-path distillation apparatus. (EtO)2P(O)CF2CF2Br
(5.80 g, 62% yield) was collected at 42-45 °C (0.3 mm Hg).
(C2H5O)2P(O)CF2CF2Cl (8). Similarly, (C2H5O)2P(O)CF2CF2Cl
was prepared from ClCF2CF2I and (EtO)2POP(OEt)2, as described above
for 7. The title compound was obtained in 53% yield (4.30 g) on
distillation (50-60 °C (0.8 mm Hg)) Via a short-path distillation
apparatus.
2
(0.05-0.02 mm Hg); 19F NMR (CDCl3) -63.9 (d, 2F, JF,F ) 7 Hz),
1
2
-112.9 (s, 2F), -119.6 (AB pattern, 2F, JF,F ) 336 Hz, JP,F ) 91
Hz), -131.3 (s, 1F); 31P{1H} NMR (CDCl3) 1.03 (t, JP,F ) 91 Hz);
2
1H NMR (CDCl3) 1.41 (t, 6H, JH,H ) 7 Hz), 4.40 (m, 4H); GC/MS
3
(70 eV) m/e (% rel intensity) 391 (M+ + 1, 37Cl, 0.3), 389 (M++1,
35Cl, 0.7), 390 (M+, 0.1), (388 (M+, 0.1), 375 (0.5), 373 (9), 363 (3),
361 (7), 359 (5), 347 (3), 345 (5), 335 (10), 333 (15), 299 (5), 297
(16), 137 (84), 109 (100), 93 (36), 91 (58), 81 (92), 69 (15); FT-IR
2986 (w), 1295 (m), 1295 (m), 1184 (s), 1162 (m), 1131 (s), 1051 (s),
1024 (s) cm-1
.
Diethyl (2-(2-fluorosulfonyltetrafluoroethoxy)tetrafluoroethyl)-
phosphonate (13, (EtO)2P(O)CF2CF2OCF2CF2SO2F): yield 2.47 g,
57%; bp 38-40 °C (0.05 mm Hg); 19F NMR (CDCl3) +45.4 (brs, 1F),
-82.2 (brs, 2F), -83.6 (m, 2F), -112.4 (s, 2F), -125.1 (d, 2F, 2JP,F
)
2
91 Hz); 31P{1H} NMR (CDCl3) -0.41 (t, JP,F ) 90 Hz); 1H NMR
3
(CDCl3) 1.41 (t, 6H, JH,H ) 7 Hz), 4.37 (m, 4H); GC/MS m/e (% rel
intensity) 437 (M+ + 1, 0.1), 421 (0.2), 409 (1), 381 (4), 297 (8), 199
(5), 181 (13), 137 (57), 119 (8), 109 (100), 100 (25), 93 (15), 91 (27),
81 (73), 69 (11), 65 (23); FT-IR 2987 (w), 1462 (s), 1297 (m), 1244
(m), 1208 (s), 1151 (vs), 1125 (m), 1025 (s) cm-1
.
Diethyl (4-(fluorosulfonyl)perfluorobutyl)phosphonate (14, (EtO)2P-
(O)(CF2)4SO2F): yield 2.1 g, 64%; bp 48-52 °C (0.01 mm Hg); 19F
NMR (CDCl3) +45.9 (d, 1F), -107.9 (s, 2F), -120.3 (s, 2F), -120.5
(s, 2F), -122.5 (dt, 2F, 2JP,F ) 90 Hz); 31P{1H} NMR (CDCl3) 0.13 (t,
2JP,F ) 91 Hz); 1H NMR (CDCl3) 1.42 (t, 6H, 3JH,H ) 7 Hz), 4.39 (m,
4H); GC/MS m/e (% rel intensity) 421 (M+ + 1, 0.1), 365 (3), 281
(3), 181 (1), 137 (40), 131 (11), 109 (100), 100 (12), 93 (16), 91 (25),
81 (47), 69 (7); FT-IR 2987 (w), 1461 (s), 1294 (m), 1238 (m), 1209
Method C. Reaction CF3CCl2I with (EtO)2POP(OEt)2. Diethyl
(1,1-dichloro-2,2,2-trifluoroethyl)phosphonate (15, (EtO)2P(O)-
CCl2CF3). In a 25 mL round-bottomed flask equipped with a septum
port, nitrogen-tee, and a magnetic stirbar was added 15 mmol of
(EtO)2POP(OEt)2. Then, 10 mmol CF3CCl2I was added dropwise (an
immediate exothermic reaction was observed), and the reaction mixture
was stirred for 30 min. To the resultant reaction mixture, 10 mL of
DMF was added, and the oxidized by Me3COOH (30 mmol) in MeOH
(20 mL) and worked up as given in method A.I. For 12: yield 1.5 g,
52 %; bp 52-55 °C (0.3 mm Hg); 19F NMR (CDCl3) -74.2 (brs);
(s), 1146 (s), 1049 (m), 1024 (vs) cm-1
.
1,3-Diiodoperfluoropropane.26 Perfluoroglutaryl chloride (75.0 g,
0.271 mol) and potassium iodide (120.0 g, 0.723 mol) were heated,
with constant mechanical stirring, in a 300 mL stainless steel pressure
reactor (Parr reactor) for 6.0 h at 200 °C and 900-1000 psi (autogenous
pressure). The Parr reactor was then cooled to room temperature, the
valve was opened to release the CO formed (Caution! in a well-
1
3
31P{1H} NMR (CDCl3) 4.90 (s); H NMR (CDCl3) 1.41 (t, 6H, JH,H

Facile Synthesis of Fluorinated Phosphonates
) 7 Hz), 4.40 (m, 4H); 13C{1H} NMR (CDCl3) 16.31 (d, JPOC,C ) 6
J. Am. Chem. Soc., Vol. 119, No. 39, 1997 9143
3
(16), 223 (64), 208 (3), 191 (3), 181 (100), 165 (16), 127 (6), 123
(78), 100 (7), 91 (3), 81 (14), 65 (9); FT-IR 2986, 2941, 1389, 1378,
1287, 1180, 1149, 1118, 1103, 1070, 1006 cm-1. Anal. Calcd. for
C8H14O3PF4I: C, 24.50; H, 3.60; P, 7.90; F, 19.38; I, 32.37. Found:
C, 24.80; H, 3.76; P, 7.89; F,19.54; I, 32.55.
2
1
2
Hz), 66.07 (d, JPOC ) 7 Hz), 76.10 (dq, JP,C ) 166Hz, JC,F ) 37
1
2
Hz), 121.70 (qd, JC,F ) 283 Hz, JP,C ) 6 Hz); GC/MS (70 eV) m/e
(% rel intensity) 289 (M+ + 1, 0.2), 273 (0.2), 259 (1), 240 (2), 151
(4), 137 (36), 132 (17), 109 (100), 93 (11), 91 (27), 81 (63); FTIR
2986 (w), 1286 (m), 1242 (m), 1200 (s), 1164 (w), 1054 (m), 1027 (s)
(EtO)2P(O)CF2CF2I (16). Similarly, a mixture of (EtO)3P (9.96
g, 60 mmol) and BrCF2CF2I (9.24 g, 30 mmol) was irradiated at 254
nm for 2.5 h at ambient temperature and worked-up as described above
for the isopropyl analogue 17. (EtO)2P(O)CF2CF2I (4.6 g, 42%) was
collected at 55-65 °C (0.10 mm Hg) Via distillation using a short-
path distillation apparatus. For 16: 19F NMR (CDCl3) -57.20 (m,
cm-1
.
Method D. Photochemical Reaction of BrCF2CF2I with Tri-
alkylphosphites. (i-C3H7O)2P(O)CF2CF2I (17). (i-C3H7O)3P (12.49
g, 60 mmol), which was freshly distilled over sodium, was introduced
Via syringe to a quartz Rotaflo tube (∼30 mL capacity) equipped with
a Teflon stopcock, under nitrogen. The tube was cooled to -196 °C
and evacuated (∼0.05 mm Hg), and BrCF2CF2I (9.24 g, 30 mmol) was
condensed on to the (i-C3H7O)3P. The Rotaflo tube was then sealed
and brought to room temperature. The reaction mixture was irradiated
at 254 nm (Rayonet photochemical apparatus) for 3.5 h at ambient
temperature and concentrated under reduced pressure (0.1-0.05 mm
Hg). The residue was extracted with 150 mL of CHCl3, washed with
water (50 mL) and brine (25 mL), concentrated on a rotary evaporator,
and chromatographed (silica gel column, eluent CH2Cl2/hexanes (20:
80)). The crude phosphonate was distilled at 55-65 °C (0.05-0.02
mm Hg), using a short-path distillation apparatus, to afford the title
compound (5.60 g, 48% yield). Spectral data: 19F NMR (CDCl3) -56.2
2
3
3
2F), -111.15 (dt, 2F), JP,F ) 95 Hz, JP,F ) 5 Hz JF,F ) 7 Hz; 31P-
{1H} NMR (CDCl3) -3.0 (tt); H NMR (CDCl3) 1.40 (t, 61H), 4.35
1
3
3
(p, (dq overlaps), 4H), JH,H ≈ JP,H ) 7 Hz. 13C{1H} NMR (CDCl3)
16.2 (d, 3JPOC,C ) 5 Hz), 65.9 (d, 2JPO,C ) 6 Hz), 97.3 (ttd, 1JC,F ) 317
Hz, 2JC,F ) 37 Hz, 2JP,C ) 14 Hz), 111.35 (tdt, 1JC,F ) 273 Hz, 1JP,C
)
201 Hz, JC,F ) 37 Hz); GC/MS m/e (% rel intensity) 364 (M+, 3),
336 (4), 322 (3), 291 (6), 209 (5), 181 (5), 138 (5), 137 (66), 131 (20),
129 (7), 127 (3), 121 (7), 119 (7), 111 (6), 110 (5), 109 (100), 100
(11), 93 (22), 91 (25), 81 (81), 69 (15), 65 (29), 51 (3); FT-IR 2987,
2934, 2915, 1443,1395, 1372, 1290, 1225, 1210, 1148, 1121, 1071,
1023 cm-1. Anal. Calcd. for C6H10O3PF4I: C, 19.80; H, 2.77; P,
8.51; F, 20.88; I, 34.86. Found: C, 19.78; H, 2.67; P, 8.23; F, 21.10;
I, 35.27.
2
2
3
3
(m, 2F), -111.5 (dt, 2F, JP,F ) 96 Hz, JP,F ) 5 Hz, JF,F ) 8 Hz;
31P{1H} NMR (CDCl3) -4.36 (tt); H NMR (CDCl3) 1.40 (d, 6H),
1
1.38 (d, 6H), 4.91 (m, 2H, JH,H ) 6 Hz). 13C{1H} (CDCl3) 23.50 (d,
3
3
2
3JPOC,C ) 6 Hz) 24.15 (d, JPOC,C ) 3 Hz), 75.49 (d, JPO,C ) 6 Hz),
Acknowledgment. We thank the National Science Founda-
tion for generous support of this work.
97.48 (ttd, 1JC,F ) 317 Hz, 2JC,F ) 40 Hz, 2JP,C ) 15 Hz), 111.13 (tdt,
1JC,F ) 274 Hz, JP,C ) 203 Hz, JC,F ) 36 Hz); GC/MS m/e (% rel
1
2
intensity) 392 (M+, 0.4), 377 (1), 349 (3), 355 (69), 309 (31), 289
JA971345T