Electrochemical partial fluorination of organic compounds. 80. Synthesis of cyclic α-arylthio-α-monofluorophosphonate esters

Article abstract of DOI:10.1021/jo051206r

Seven-membered cyclic α-monofluorophosphonate esters such as 2-allyloxy-3-fluoro-3-phenylthio-4,7-dihydro-[1, 2]-oxaphosphinine-2-oxide were successfully synthesized in moderate total yield as 41% from open-chain allyl phosphonates having an α-arylthio group as an electroauxiliary using an alternative sequence of anodic fluorination and ring-closing olefin metathesis (RCM). On the other hand, in an attempt to synthesize an eight-membered analogue, a different type of seven-membered fluorinated cyclic product was formed predominantly by the RCM reaction between the allyloxy groups.

Full text of DOI:10.1021/jo051206r

Electrochemical Partial Fluorination of
Organic Compounds. 80.
Synthesis of Cyclic
r-Arylthio-r-monofluorophosphonate
Esters
FIGURE 1. First- (A) and second-generation (B) Grubbs’
catalysts.
Yi Cao, Asami Hidaka, Toshiki Tajima, and
Toshio Fuchigami*
to exhibit better bioactivity than the corresponding
nonfluorinated phosphonates.5 It has also been suggested
that the R-monofluorophosphonates gave superior results
to R,R-difluorination in phosphonate mimics of biological
phosphates.6 Therefore, in recent years, many efforts
have been devoted to construct phosphonate mimics with
R-fluoro- and R,R-difluoromethylene groups as an iso-
electronic and isosteric replacement for oxygen in phos-
phate groups. On the other hand, compounds having an
ArSCHF moiety are considered to be fluoropeptido mi-
metics, and they show protease inhibition.7
Department of Electric Chemistry, Tokyo Institute of
Technology, 4259 Nagatsuta, Midori-ku,
Yokohama, 226-8502, Japan
fuchi@echem.titech.ac.jp
Received June 14, 2005
N,N-Diethylaminosulfurtrifluoride (DAST) has been
mainly used for the preparation of R-mono- and R,R-
difluorophosphonates from R-hydroxy- and R-ketophos-
phonates, respectively.6,8 However, a serious drawback
of DAST is that it is expensive and sometimes explosive.
On the other hand, selective electrochemical fluorination
has been shown to be a highly efficient tool for the
synthesis of various fluorinated organic sulfur com-
pounds9 with the advantage of mild conditions and
avoidance of hazardous and explosive reagents.
The ring-closing olefin metathesis (RCM) reaction has
been recognized as a powerful method for the preparation
of medium- or large-sized rings to create heterocycles,
constrained peptides, and complex natural products.10
Grubbs’ ruthenium catalysts A11a and B,11b as shown in
Figure 1, have been used most widely in RCM reactions
because of their high reactivity, air stability, and re-
Seven-membered cyclic R-monofluorophosphonate esters
such as 2-allyloxy-3-fluoro-3-phenylthio-4,7-dihydro-[1, 2]-oxa-
phosphinine-2-oxide were successfully synthesized in moder-
ate total yield as 41% from open-chain allyl phosphonates
having an R-arylthio group as an electroauxiliary using an
alternative sequence of anodic fluorination and ring-closing
olefin metathesis (RCM). On the other hand, in an attempt
to synthesize an eight-membered analogue, a different type
of seven-membered fluorinated cyclic product was formed
predominantly by the RCM reaction between the allyloxy
groups.
(4) See, for example: (a) Burke, T. R., Jr.; Kole, H. K.; Roller, P. P.
Biochem. Biophys. Res. Commun. 1994, 204, 129-134. (b) Halazy, S.;
Ehrhard, A.; Eggenspiller, A.; Berges-Gross, V.; Danzin, C. Tetrahedron
1996, 52, 172-184. (c) Higashimoto, Y.; Saito, S.; Tong, X.-H.; Hong,
A.; Sakaguchi, K.; Appella, E.; Anderson, C. W. J. Biol. Chem. 2000,
275, 23199-23203.
(5) (a) Lequeux, T.; Lebouc, F.; Lopin, C.; Yang, H.; Gouhier, G.;
Piettre, S. R. Org. Lett. 2001, 3, 185-188. (b) Taylor, S. D.; Kotoris, C.
C.; Dinaut, A. N.; Chen, M. J. Tetrahedron 1998, 54, 1691-1714.
(6) See, for example: (a) Berkowitz, D. B.; Bose, M.; Pfannenstied,
T. J.; Doukov, T. J. Org. Chem. 2000, 65, 4498-4508. (b) Berkowitz,
D. B.; Bose, M. J. Fluorine Chem. 2001, 112, 13-33.
(7) Annedi, S. C.; Majumder, K.; Wei, L.; Oyiliagu, C. E.; Samson,
S.; Kotra, L. P. Bioorg. Med. Chem. 2005, 13, 2943-2958.
(8) (a) Smith, M. S.; Burke, T. R. Tetrahedron 1994, 35, 551-554.
(b) Solas, D.; Hale, R. D.; Patel, D. V. J. Org. Chem. 1996, 61, 1537-
1539.
(9) (a) Fuchigami, T. Organic Electrochemistry, 4th ed.; Lund, H.,
Hammerich, O., Eds.; Marcel Dekker: New York, 2000; Chapter 25.
(b) Suzuki, K.; Fuchigami, T. J. Org. Chem. 2004, 69, 1276-1282. (c)
Dawood, K. M.; Fuchigami, T. J. Org. Chem. 2004, 69, 5302-5306.
(d) Hasegawa, M.; Ishii, H.; Fuchigami, T. Green Chem. 2003, 5, 512-
515.
Cyclic phosphonates play critical roles in a wide variety
of biochemical processes such as carbohydrate-linked
biological process (e.g. cellular recognition).1,2 On the
other hand, cyclic allylic phosphonates have enormous
potential in the development of novel phosphonates,
phosphonic acids, phosphinates, phosphonosugars, and
conformationally restricted phosphonic acid.3
Many studies indicated that the presence of the
fluorine atoms at the R-position of phosphorus in phos-
phonate increased both the structural and electronic
similarities to the parent phosphate groups.4 Moreover,
several analogues of phosphates encompassing the di-
fluoromethylene-phosphonate moiety have been shown
(1) (a) Darrow, J. W.; Drueckhammer, D. G. J. Org. Chem. 1994,
59, 2976-2985. (b) Hannessian, S.; Galeotti, N.; Rosen, P.; Olva, G.;
Babu, S. Bioorg. Med. Chem. 1994, 23, 2763.
(2) Rademacher, T. W.; Parekh, R. B.; Dwek, R. A. Annu. Rev.
Biochem. 1998, 57, 785.
(3) (a) Hanson, P. R.; Stoianova, D. S. Tetrahedron Lett. 1998, 39,
3939-3942. (b) Wang, Q.; Pfeiffer, B.; Tucker, G. C.; Royer, J.; Husson,
H.-P. Bioorg. Med. Chem. Lett. 1997, 7, 2477 (c) Gao, J.; Martichonok,
V.; Whitesides, G. M. J. Org. Chem. 1996, 61, 9538. (d) Natchev, I. A.
Bull. Chem. Soc. Jpn. 1988, 61, 3705 and 3711. (e) Natchev, I. A. J.
Chem. Soc., Perkin Trans. 1 1989, 125.
(10) For recent reviews on RCM, see: (a) Furstner, A. Angew. Chem.,
Int. Ed. 2000, 39, 3012-3043. (b) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18-29. (c) Love, J. A.; Sanford, M. S.; Day, M.
W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 10103-10109. (d) Grubbs,
R. H. Tetrahedron 2004, 60, 7117-7140.
(11) (a) Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1993, 115,
9858-9859. (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953-956.
10.1021/jo051206r CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/20/2005
9614
J. Org. Chem. 2005, 70, 9614-9617

TABLE 1. Anodic Fluorination of Diallyl
SCHEME 1. Retrosynthetic Analysis of
Fluorinated Cyclic Phosphonate Esters
r-Phenylthio-3-butenylphosphonate (4a)a
supporting
electrolyte (1 M)
entry
solvent
yield (%)b
1
2
3
4
DME
Et4NF-3HF
Et3N-3HF
Et3N-5HF
Et4NF-3HF
64 (53)
21c
DME
DME
CH3CN
4c
0c
a Constant current: 20 mA/cm2; electricity: 12 F/mol. b Deter-
mined by 19F NMR. The number in parentheses is the isolated
yield. c The starting material was mostly recovered.
markable functional group tolerance. Recently, it was
shown that the RCM reaction by using Grubbs’ catalyst
A is an effective method for the construction of phospho-
rus-containing cyclic compounds.3a,12 It has also been
found that Grubbs’ catalyst B was more efficient in the
RCM reaction of sulfur-containing compounds.13 Al-
though there has been only one report on the synthesis
of cyclic R,R-difluorophosphonates using bromodifluoro-
phosphonate as a building block,14 a combination of the
RCM reaction and anodic fluorination has never been
used, to our knowledge, for the preparation of R-mono-
fluorinated cyclic phosphonates.
In this Note, we describe the synthesis of 2-allyoxy-3-
fluoro-3-arylthiocyclic phosphonate esters using both
electrolysis and the RCM reaction. The retrosynthetic
analysis of our strategy is shown in Scheme 1. Two
possible synthetic routes, namely, an alternative se-
quence of electrolysis and the RCM reaction from open-
chain diallyl (1-arylthio-3-butenyl) phosphonate 4, were
considered. It is of much interest to compare the RCM
reactivity of the fluorinated and nonfluorinated open-
chain diallyl phosphonate derivatives and also the anodic
fluorination of open-chain and the corresponding cyclic
phosphonate derivatives.
The starting material, diallyl R-arylthio-olefinic phos-
phonates 4, was prepared by allylation of diethyl (R-
arylthio)-methylphosphonate, followed by the three-step
transesterification procedure outlined in the literature.15
Initially, anodic fluorination of diallyl 1-phenylthio-3-
butenylphosphonate (4a) was investigated at a constant
current by using an undivided cell and platinum elec-
trodes. Various quaternary ammonium fluorinate salts
were used as a supporting electrolyte and a fluoride ion
source, as shown in Table 1. The monofluorination of 4a
proceeded smoothly in Et4NF-3HF/dimethoxyethane
(DME) to give the maximum yield (64%) of the mono-
fluorinated product 3a (Table 1, entry 1). The use of other
supporting electrolytes resulted in much lower yields of
3a, and the starting material 4a was recovered consider-
ably (Table 1, entries 2 and 3). The fluorination of 4a
did not proceed at all in CH3CN.
TABLE 2. RCM Reaction of Open-Chain Phosphonates
3 and 4
substrate
reaction
yield (%)a
entry
Ar
X
No. catalyst time (h)
1
2
3
4
5
6
C6H5
H
F
4a
3a
4b
4a
3a
4b
A
A
A
B
B
B
4
0.5
4
4
0.5
4
0b
45 (1:2.7) 1a
0b
2b
2a
C6H5
ClC6H4
C6H5
C6H5
ClC6H4
H
H
F
71 (1:1.4) 2a
42 (1:3)
77 (1:1)
1a
2b
H
a Isolated yield. Numbers in parentheses are diastereoisomeric
ratios. b The starting material was mostly recovered.
Next, the RCM reaction was carried out in refluxing
CH2Cl2 containing 5 mol % Grubbs’ catalyst. As shown
in Table 2, the ring-closing reaction of 4a did not proceed
at all by using catalyst A (Table 2, entry 1). This is
probably because of the deactivation of the catalyst by
complexation of the Ru metal with a sulfur atom of 4a.16
To suppress such complexation, diallyl 3-butenylphos-
phonate having an electron-withdrawing p-chlorophen-
ylthio group at the R-position of 4b was used for the RCM
reaction. However, the RCM reaction did not proceed at
all, and the starting 4b was mostly recovered (Table 2,
entry 3).
In sharp contrast, monofluorinated phosphonate 3a
provided the target cyclic fluorinated product 1a as a
diastereoisomeric mixture in moderate yield (Table 2,
entry 2). This can be explained in terms of the suppres-
sion of the formation of a complex of the catalyst metal
with the sulfur atom of 3a owing to the decrease of the
electron density of the sulfur atom by the strongly
electron-withdrawing fluorine atom at the R-position of
3a. Hanson and co-workers found a similar effect of an
R-electron-withdrawing ester group on the RCM reaction
of sulfides.16 On the other hand, even nonfluorinated
phosphonates 4a and 4b underwent the RCM reactions
(12) (a) Hetherington, L.; Greedy, B.; Gouverneur, V. Tetrahedron
2000, 56, 2053-2060. (b) Stoianova, D. S.; Hanson, P. R. Org. Lett.
2001, 3, 3285-3288.
(13) Spagnol, G.; Heck, M.-P.; Nalan, S. P.; Mioskowski, C. Org. Lett.
2002, 4, 1767-1770.
(14) Butt, A. H.; Percy, J. M.; Spencer, N. S. Chem. Commun. 2000,
1691-1692.
(15) Skropeta, D.; Schmidt, R. R. Tetrahedron: Asymmetry 2003,
14, 265-273.
(16) Moore, J. D.; Sprott, K. T.; Hanson, P. R. Synlett 2001, 605-
608.
J. Org. Chem, Vol. 70, No. 23, 2005 9615

TABLE 3. Anodic Fluorination of Cyclic
Phosphonates 2a
SCHEME 2. Anodic Oxidation and RCM Reaction
of Diallyl r-Phenylthio-3-pentenylphosphonate (5)
substrate
entry
Ar
No.
yield (%)b
1
2
C6H5
ClC6H4
2a
2b
58 (45)c
1a
1b
45 (38)d
a Constant current: 20 mA/cm2; electricity: 12 F/mol. b Deter-
mined by 19F NMR. Numbers in parentheses are isolated yields.
c Diastereoisomeric ratio ) (1:2.3). d Diastereoisomeric ratio )
(1:2.2).
in the presence of the second-generation Grubbs’ catalyst
B to provide the cyclic products 2a and 2b in relatively
good yields (Table 2, entries 4 and 6). It was expected
that the fluorinated phosphonate 3a would provide
similarly high yield of cyclic product 1a in the presence
of catalyst B. However, the yield was not increased and
was almost the same as that obtained in the presence of
catalyst A (Table 2, entry 5). Although diastereoselec-
tivity was not observed in the RCM reaction of nonflu-
orinated phosphonates 4a and 4b, the R-fluorine atom
of the phosphonate 3a affected the diastereoselectivity
of the RCM reaction appreciably. Almost the same
diastereomeric ratio (ca. 1:3) was obtained regardless of
the catalysts.
SCHEME 3. Chemical Fluorination of Diallyl
r-Phenylthio-3-butenylphosphonate (4a)
Next, an alternative synthesis of R-fluorinated cyclic
phosphonates 1 was attempted according to route B in
Scheme 1. Anodic fluorination of the cyclic phosphonates
2 was carried out under the optimum electrolytic condi-
tions for the case of 4a (Table 1, entry 1). The target
products 1 were obtained in moderate yields regardless
of the substituents on the benzene ring of the arylthio
groups as shown in Table 3. The diastereoisomeric ratios
of products 1a and 1b were almost the same and also
were similar to that of 1a derived from 3a (Table 2,
entries 2 and 5). The total yield (41%) of cyclic R-fluoro-
phosphonate 1a from 4a by route B was found to be
higher than that obtained by route A (29% yield).
Therefore, route B is more efficient than route A due to
the higher reactivity of nonfluorinated open-chain phos-
phonate in the RCM reaction compared with fluorinated
phosphonate. In addition, it was also found that the
diastereoisomeric ratio was similar in both routes.
Furthermore, the preparation of eight-membered cyclic
R-fluorophosphonate ester was also attempted in a
similar manner. The anodic fluorination of diallyl R-phen-
ylthio-4-pentenylphosphonate (5) gave extremely low
yield. After many attempts under various electrolytic
conditions, the fluorinated product 6 was obtained in 20%
yield as the maximum yield in Et4NF-3HF/DME at a
higher current density after an extremely large excess
amount of electricity was passed owing to its high
oxidation potential [decomposition potential (Edox): ca.
2.2 V versus SCE] as shown in Scheme 2. The reason for
the extremely higher oxidation potential of 5 compared
with that of 4a is not clear. However, such a high
oxidation potential of 5 may be attributable to the steric
hindrance of a 4-pentenyl group.
The RCM reaction of 6 thus obtained was carried out
as shown in Scheme 2. In sharp contrast to 4a, the RCM
reaction took place between two allyloxy chains to provide
seven-membered cyclic phosphonate ester 8 instead of the
expected eight-membered analogue to 1a. Boom and co-
workers also reported that the formation of a smaller size
cycle was first favored among five-, six-, and seven-
membered cycles in the synthesis of phosphorus bicycles
by RCM reaction.17 The use of catalyst A resulted in low
yield of 8, and a large amount of starting 6 was recovered.
However, the yield was increased considerably to 60%
by using catalyst B. Alternatively, the RCM reaction of
nonfluorinated substrate 5 was also carried out. In the
presence of catalyst A, the RCM reaction did not proceed
and the starting material 5 was mostly recovered similar
to the case of 4a. On the other hand, the RCM reaction
proceeded by using catalyst B; however, the cyclization
took place between two allyloxy chains in a manner
similar to the case of fluorinated substrate 6 to provide
7 in moderate yield (49%). The RCM product 7 was
subjected to anodic fluorination in the same electrolytic
solution as used for 5, and the corresponding fluorinated
product 8 was obtained in reasonable yield (21%).
Finally, we attempted the chemical fluorination of 4a
using various selecfluor18 and N-fluoropyridinium salts
C-E19 as shown in Scheme 3, since these fluorinating
reagents are well-known to be effective for the R-fluori-
(17) Timmer, M. S. M.; Ovaa, H.; Filippov, D. V.; Marel, G. A.; Boom,
J. H. Tetrahedron Lett. 2001 42, 8231-8233.
(18) Lal, G. S. J. Org. Chem. 1993, 58, 2791-2796.
(19) (a) Umemoto, T.; Tomizawa, G. Bull. Chem. Soc. Jpn. 1986,
59, 3625-3629. (b) Umemoto, T.; Tomizawa, G. J. Org. Chem. 1995,
60, 6563-6570.
9616 J. Org. Chem., Vol. 70, No. 23, 2005

major), 44.88 (d, JCP ) 133.9 Hz, minor), 63.05 (d, JCP ) 5.56
Hz, major), 63.46 (d, JCP ) 5.02 Hz, minor), 67.19 (d, JCP ) 6.71
Hz, major), 67.36 (d, JCP ) 6.17 Hz, minor), 118.2, 127.6, 128.5,
129.0, 130.5, 132.2 (d, JCP ) 17.3 Hz), 132.5; MS m/z 296 (M+),
255 (M+ - CH2CHCH2), 187 (M+ - SC6H5); HRMS m/z calcd
for C14H17O3PS: 296.0636. Found: 296.0631.
2-Allyloxy-3-(para-chlorophenyl)thio-4,7-dihydro-[1,2]-
oxaphosphinine-2-oxide (2b): yellow oil; diastereomer mix-
ture; 1H NMR (CDCl3) δ 2.53-2.79 (m, 2H), 3.30-3.41 (m, 1H),
4.43-4.76 (m, 4H), 5.24-5.39 (m, 2H), 5.84-6.01 (m, 3H), 7.27-
7.48 (m, 4H); 13C NMR δ 28.84 (0.5C), 29.30 (0.5C), 44.42 (d,
JCP ) 136 Hz, 0.5C), 44.99 (d, JCP ) 134 Hz, 0.5C), 63.06 (d,
JCP ) 5.01 Hz, 0.5C), 63.40 (d, JCP ) 5.02 Hz, 0.5C), 67.05 (d,
JCP ) 6.71 Hz, 0.5C), 67.18 (d, JCP ) 6.64 Hz, 0.5C), 118.3, 128.6,
129.1, 130.7, 132.2 (d, JCP ) 11.7 Hz), 133.9 MS m/z 330 (M+),
187 (M+ - SC6H4Cl); HRMS m/z calcd for C14H16ClO3PS:
330.0246. Found: 330.0237.
nation of sulfides. However, the fluorination did not
proceed at all. In all cases, the starting material was
mostly recovered.
In conclusion, seven-membered cyclic monofluorophos-
phonate esters were successfully synthesized from open-
chain allyl phosphonates having an R-arylthio group
using anodic fluorination, followed by ring-closing olefin
metathesis with the first-generation Grubbs’ catalyst A.
Alternatively, allyl phosphonates having an R-arylthio
group were transformed to cyclic phosphonates using the
second-generation Grubbs’ catalyst B, and subsequently
the cyclic phosphonates were subjected to anodic fluori-
nation to provide the desired same fluorinated products.
The latter route was found to be more efficient. However,
in an attempt to synthesize an eight-membered analogue,
the RCM reaction proceeded in a different manner and
the allyloxy ring-closing product was obtained solely
instead of the expected analogue of 1. The fluorinated
cyclic phosphonates 1 and 8 thus prepared are expected
to have unique biological activity.
Diallyl r-fluoro-(r-phenylthio)-3-butenylphosphonate
(3a): yellow oil; 1H NMR (CDCl3 ) δ 2.86 (m, 2H), 4.57 (m, 4H),
5.08-5.36 (m, 6H), 5.88 (m, 3H), 7.27-7.63 (m, 5H); 13C NMR δ
34.30, 67.19 (dd, JCP ) 17.90, JCF ) 6.71 Hz), 69.9 (dd, JCP
)
17.90, JCF ) 6.71 Hz), 103.9 (d, JCF ) 175 Hz) 117.8, 119.4, 127.4,
128.7, 131.9, 132.2 (d, JCP ) 6.10 Hz), 132.7 (d, JCP ) 6.10 Hz)
134.1 (d, JCP ) 11.7 Hz), 136.3; 19F NMR (CDCl3) δ -62.9 (dt,
JPF ) 98.1 Hz, JHF ) 16.6 Hz); MS m/z 342 (M+), 322 (M+
-
-
HF), 281 (M+ - CH2CHCH2/HF); HRMS (m/z) calcd for C16H20
Experimental Section
FO3PS: 342.0855. Found: 324.0860.
General experimental details can be found in Supporting
Information.
Diallyl r-fluoro-(r-phenylthio)-4-pentenylphosphonate
(6): yellow oil; 1H NMR (CDCl3 ) δ 2.00-2.18 (m, 2H) 2.34-
2.40 (m, 2H), 4.58 (m, 4H), 4.92-5.00 (m, 2H), 5.22-5.37 (m,
4H), 5.62-5.93 (m, 3H), 7.26-7.63 (m, 5H); 13C NMR δ 28.20,
35.18 (d, JCP ) 5.02 Hz), 67.96 (dd, JCP ) 15.1 Hz, JCF ) 5.01
Hz), 68.05 (dd, JCP ) 15.2 Hz, JCF ) 5.02 Hz), 102.2 (JCF ) 241
Hz), 115.2, 118.4, 128.7, 128.8, 131.8, 132.2 (d, JCP ) 6.78 Hz),
132.3 (d, JCP ) 6.67 Hz) 135.8 (d, JCP ) 2.32 Hz), 136.4; 19F NMR
(CDCl3) δ -63.0 (dt, JPF ) 99.0 Hz, JHF ) 16.8 Hz); MS m/z 356
(M+), 236 (M+ - HF), 172 (M+ - HF/SC6H5/CH2CH2CHCH2);
HRMS (m/z) calcd for C17H22FO3PS: 356.1011. Found: 356.1013.
2-(1-Phenylthio-4-pentenyl)-4,7-dihydro-[1,3,2]dioxaphos-
phepine-2-oxide (7): yellow oil; 1H NMR (CDCl3) δ 1.87 (m,
1H), 1.97-2.19 (m, 1H), 2.27-2.49 (m, 2H), 3.30 (m, 1H), 4.46-
5.04 (m, 6H), 5.70-5.85 (m, 3H), 7.27-7.54 (m, 5H); 13C NMR δ
28.84, 30.57 (JCP ) 11.7 Hz), 42.65 (d, JCP ) 145 Hz), 64.44 (d,
JCP ) 7.80 Hz), 64.85 (d, JCP ) 8.41 Hz), 116.1, 127.2, 127.3,
127.5, 128.8, 130.5, 132.1, 134.2 (d, JCP ) 2.85 Hz), 136.5; MS
m/z 310 (M+), 256 (M+ - CH2CHCHCH2), 201 (M+ - SC6H5);
HRMS m/z calcd for C15H19O3PS: 310.0793. Found: 310.0789.
2-(1-Fluoro-1-phenylthio-4-pentenyl)-4,7-dihydro-[1,3,2]-
dioxaphosphepine-2-oxide (8): yellow oil; 1H NMR (CDCl3)
δ 2.16-2.46 (m, 4H), 4.08-4.30 (m, 2H), 4.47-5.05 (m, 4H),
5.60-5.85 (m, 3H), 7.26-7.68 (m, 5H); 13C NMR δ 23.06, 29.77,
65.05 (d, JCP ) 6.71 Hz), 65.19 (d, JCP ) 2.77 Hz), 105.2 (d,
JCF ) 237 Hz) 115.4, 126.9, 127.0, 128.7, 129.7, 136.6, 136.8 (d,
JCP ) 1.15 Hz); 19F NMR (CDCl3) -63.37 (dd, JPF ) 92.5 Hz,
Electrolytic Procedure for Fluorination. A typical pro-
cedure is as follows. Anodic fluorination of phosphonates (0.2
mmol) was carried out with platinum plate electrodes (2 × 2
cm2) in a solvent (10 mL) containing a fluoride salt (1 M) using
an undivided cell at room temperature. Constant current (20
mA/cm2) was passed until the starting material was consumed
(monitored by TLC). The cell voltage during the electrolysis was
ca. 10 V. After the electrolysis, the resulting electrolytic solution
was passed through a short column of silica gel eluting with
AcOEt to remove the fluoride salt. The eluent was evaporated
under vacuum, and the residue was purified by silica gel column
chromatography using AcOEt and hexane (5:1-1:1) to give pure
fluorinated products. The products were identified by spectral
data.
Ring-Closing Metathesis Reaction. Under a nitrogen
atmosphere to a solution of diallyl phosphonate in dry CH2Cl2
(0.02 M) was added dropwise the Grubbs’ catalyst A or B (5 mol
%). The solution was refluxed until maximum conversion as
shown by TLC. The solvent was removed under vacuum and
purified by column chromatography eluting with AcOEt and
hexane (10:1-5:1).
2-Allyloxy-3-fluoro-3-phenylthio-4,7-dihydro-[1,2]oxa-
phosphinine-2-oxide (1a): yellow oil; diastereomer mixture;
1H NMR (CDCl3) δ 2.59-2.95 (m, 2H), 4.50-4.83 (m, 4H), 5.22-
5.46 (m, 2H), 5.65 (m, 1H), 5.93 (m, 2H), 7.34-7.65 (m, 5H); 19
F
JHF ) 18.3 Hz), MS m/z 328 (M+), HRMS m/z calcd for C15H18
FO3PS: 328.0698. Found: 328.0702.
-
NMR (CDCl3) δ -53.1 (dd, JPF ) 82.6 Hz, JHF ) 20.3 Hz, major),
-51.8 (dd, JPF ) 92.5 Hz, JHF ) 18.5 Hz, minor), MS m/z 314
(M+), 294 (M+ - HF), 185 (M+ - HF/SC6H5); HRMS m/z calcd
for C14H16FO3PS: 314.0541. Found: 314.0542
Acknowledgment. This research was supported by
a Grant-in-Aid for Scientific Research on Priority Areas
(A) “Exploitation of Multi-Element Cyclic Molecules”
from the Ministry of Education, Culture, Sports, Science
and Technology, Japan. We also thank Prof. Piettre of
the University of Rouen for his valuable suggestions.
2-Allyloxy-3-fluoro-3-(para-chlorophenyl)thio-4,7-dihy-
dro-[1,2]oxaphosphinine-2-oxide (1b): yellow oil; diastereo-
mer mixture; 1H NMR (CDCl3) δ 2.34-2.97 (m, 2H), 4.50-4.86
(m, 4H), 5.23-5.45 (m, 2H), 5.67-6.01 (m, 3H), 7.26-7.64 (m,
4H); 13C NMR δ 29.62, 63.56 (d, JCP ) 5.02 Hz, major), 64.48 (d,
JCP ) 5.56 Hz, minor), 67.09 (d, JCP ) 6.64 Hz, major), 68.36 (d,
JCP ) 6.64 Hz, minor), 118.5, 126.0, 129.0, 130.8, 131.8 (d,
JCP ) 6.17 Hz), 137.5; 19F NMR (CDCl3) -54.2 (dd, JPF ) 81.3
Hz, JHF ) 18.5 Hz, major), -53.1 (dd, JPF ) 92.5 Hz, JHF ) 18.5
Hz, minor); MS m/z 348 (M+), 330 (M+ + H - F); HRMS m/z
calcd for C14H15ClFO3PS: 348.0152. Found: 348.0146.
2-Allyloxy-3-phenylthio-4,7-dihydro-[1,2]oxaphosphin-
ine-2-oxide (2a): yellow oil; diastereomer mixture; 1H NMR
(CDCl3) δ 2.56-2.80 (m, 2H), 3.36-3.60 (m, 1H), 4.43-4.76 (m,
4H), 5.22-5.42 (m, 2H), 5.89 (m, 3H), 7.27-7.52 (m, 5H); 13C
NMR δ 29.72 (major), 30.18 (minor), 44.38 (d, JCP ) 136.1 Hz,
Supporting Information Available: General part and
general experimental method; synthetic procedures for the
starting materials 4a, 4b, and 5; spectroscopy data and
analytical data of compounds 4a, 4b, 5, and the unknown
compounds of intermediates in the synthesis of the starting
materials; NMR spectra of 1-8 and other unknown compounds
without elemental analysis. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO051206R
J. Org. Chem, Vol. 70, No. 23, 2005 9617