2216
T. Sierakowski, J. J. Kiddle / Tetrahedron Letters 46 (2005) 2215–2217
Table 1. Synthesis of phosphorus(V) fluoride compounds using a solid-supported reagent22
X
X
P
R
Amberlyst A-26 [F-]
P
R
Cl
R
F
THF, rt
R
R
X
Time (h)
Isolated yielda (%)
31P NMR db
19FNMR db
CH3O
O
O
S
0.5
0.5
2.0
0.5
1.0
2.5
82
81
91
76
70
81
À8.46 (1JP–F = 973 Hz)
À8.0 (1JP–F = 990 Hz)
62.9 (1JP–F = 1082 Hz)
À10.2 (1JP–F = 978 Hz)
À21.0 (1JP–F = 1002 Hz)
18.3 (1JP–F = 947 Hz)
À80.0 (1JF–P = 984 Hz)
À77.3 (1JF–P = 982 Hz)
À43.7 (1JF–P = 1076 Hz)
À76.8 (1JF–P = 977 Hz)
À76.9 (1JF–P = 997 Hz)
À82.8 (1JF–P = 943 Hz)
CH3CH2O
CH3CH2O
(CH3)2CHO
PhO
O
O
O
(CH3)2N
a All reactions showed 100% conversion by 31P NMR prior to isolation.
b All compounds demonstrated satisfactory 1H, 13C, 19F, and 31P NMR data and were compared with literature values as well as authentic samples.
to furnish the products of both fluorination and oxida-
tions in excellent yields [FP(O)].14 Unfortunately, the
yields reported were calculated from 31P NMR data
and may not reflect the isolated yield of the products.
Additionally, not all of the starting compounds are com-
mercially available requiring the synthesis of precursors
for these transformations.
(78%). In general, the reduction in isolated yield for
the reactions, despite all showing complete conversion
by 31P NMR spectroscopy, is attributed to retention
of the product on the resin, and loss of material during
the solvent removal.
In conclusion, we have developed an efficient synthesis
of a variety of phosphorus(V) fluorides from the corre-
sponding chlorides utilizing a solid-supported source
of fluoride ion at room temperature. This methodology
represents a simplified procedure over those previously
reported avoiding the need to synthesize starting materi-
als to construct the phosphorus(V) fluorides. More
importantly, this reaction sequence minimizes exposure
to both the starting material and product, which are
both potent acetylcholinesterase inhibitors, and offers
the rapid isolation of the pure product by filtration.
The use of solid-supported reagents in organic synthesis
is a rapidly developing area of growth.15–21 Solid-sup-
ported reagents often perform in a similar fashion to
their unbound equivalents, but with reduced solvent
requirements. In addition, the increased reagent surface
area can improve the reactivity of a particular reagent.
Because of the deficiencies in the available methods for
the synthesis of phosphorus(V) fluorides, we sought to
develop a more efficient method for their syntheses from
commercially available phosphorus(V) chlorides using a
solid-supported fluoride reagent.
Acknowledgements
As a first attempt, we examined the equal molar reaction
of diethyl chlorophosphate with the ion exchange resin
AmberlystÒ A-26 with a fluoride counterion in THFat
room temperature. The reaction was followed by 31P
NMR at 15 min intervals and showed complete conver-
sion of the diethyl chlorophosphate (31P NMR d =
5.0 ppm) to the corresponding diethyl fluorophosphates
(31P NMR d = À8.0 ppm, d, JP–F = 990 Hz) in 30 min.
Filtration of the heterogeneous reaction mixture and
concentration of the solvent provided the pure phospho-
rus(V) fluoride in 81% isolated yield.
The authors thank the College of Arts and Sciences at
Western Michigan University for support of this
research.
References and notes
1. Saunders, B. C. Some Aspects of the Chemistry and Toxic
Action of Organic Compounds Containing Phosphorus and
Fluorine; Cambridge University Press: Cambridge, 1957.
2. DeFrank, J. J. In Applications of Enzyme Biotechnology;
Kelly, J. W., Baldwin, T. O., Eds.; Plenum: New York,
1991; pp 165–180.
3. Kiddle, J. J.; Mezyk, S. P. J. Phys. Chem. A 2004, 108,
9568–9570.
´
4. Michalski, J.; Łopusinski, A. Angew. Chem., Int. Ed. Engl.
With this result in hand, a series of disubstituted phos-
phorus(V) chlorides were chosen as substrates and re-
acted under identical conditions to the model system
to afford the corresponding phosphorus(V) fluorides in
very good isolated yields (Table 1).
1982, 21, 294.
5. Konieczko, W. T.; Łopusinski, A.; Michalski, J. Phospho-
´
rus, Sulfur, Silicon Rel. Elem. 1989, 42, 103–104.
6. Dabkowski, W.; Cramer, F.; Michalski, J. Tetrahedron
Lett. 1987, 28, 3561–3562.
7. Dabkowski, W.; Cramer, F.; Wasiak, J.; Michalski, J. J.
Chem. Soc., Perkin Trans. 1 1994, 817–820.
As revealed in Table 1, all the phosphorus(V) chlorides
reacted smoothly in short reaction times to produce the
corresponding phosphorus(V) fluorides in very good
yields. The procedure was tolerant of both the ligands
on phosphorus and the chalcogen atom bonded to the
phosphorus. In addition, scale up of the procedure
(2.8–28 mmol) did not show any significant change in
the isolated yield for the diethyl fluorophosphate
8. Dabkowski, W.; Michalski, J.; Skrzypczynski, Z. Phos-
phorus, Sulfur, Silicon Rel. Elem. 1986, 26, 321–326.
´
9. Łopusinski, A. Phosphorus, Sulfur, Silicon Rel. Elem.
1989, 45, 137–143.