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LETTER
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when they were at the 2-position of aromatic rings. For
example, there was a decrease in yield of the 2-nitro de-
rivative 4i (30%) compared to the 3-nitro 4g and 4-nitro
4k derivatives (92% and 77%, respectively). This de-
crease in yield could be attributed to the increased steric
demands of the 2-substituted phosphonates. Under these
conditions, the step of deprotonation to form carbanions
was slowed down because of a difficult approach of NaH-
MDS in a highly crowded position.
In summary, we have developed an efficient and practical
approach for the preparation of diethyl a-chloro-a-fluo-
robenzylphosphonates from simple carbonyl compounds.
These compounds can be converted into various useful
quaternary carbon-containing a-fluorophosphonates by
using nucleophilic substitution. Attempts toward the
asymmetric version of the reaction as well as the exten-
sion of this method are currently under way.
(10) Iorga, B.; Eymery, F.; Savignac, P. Tetrahedron Lett. 1998,
39, 3693.
(11) General Procedure for the Preparation of a-Chloro-
benzylphosphonates from a-Hydroxyphosphonates
A solution of 1k (1.00 g, 3.46 mmol, 1.0 equiv) and Ph3P
(1.36 g, 5.19 mmol, 1.5 equiv) in dry CCl4 (10 mL) is
refluxed for 8 h under argon. Then, the mixture is evaporated
under reduced pressure, and the semisolid residue is
extracted with PE. The combined extracts are filtered, and
the solvent is removed under reduced pressure. The crude
material was purified by flash column chromatography on
silica gel to yield 3k as yellow oil (0.81 g, 76%). 1H NMR
(300 MHz, CDCl3): d = 1.26 (t, J = 7.0 Hz, 3 H), 1.35 (t,
J = 7.0 Hz, 3 H), 4.00–4.14 (m, 2 H), 4.15–4.28 (m, 2 H),
5.00 (d, 2JPH = 15.2 Hz, 1 H), 7.73 (d, J = 8.6 Hz, 2 H), 8.25
(d, J = 8.6 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3):
d = 16.2 (d, 3JPC = 5.6 Hz), 16.4 (d, 3JPC = 5.7 Hz), 52.5 (d,
1JPC = 156.4 Hz), 64.1 (d, 2JPC = 7.0 Hz), 64.6 (d, 2JPC = 7.0
Hz), 123.6, 129.8, 141.4, 148.0 ppm.
Supporting Information for this article is available online at
Acknowledgment
We are grateful to the Natural Science Foundation Project of CQ
CSTC (No. CSTC, 2006BB5052) and the Southwest University
Science Foundation for Doctoral Scientists (SWNUB2005013) for
financial support.
References and Notes
(12) General Procedure for the Preparation of a,a-Chloro-
fluorobenzylphosphonates from a-Chlorophosphonates
To a solution of the a-chlorophosphonates 3k (0.31 g, 0.94
mmol, 1.0 equiv) in dry THF (10 mL) at –78 °C was added
dropwise a solution of NaHMDS (1.69 mmol, 2.0 M in THF,
1.5 equiv) in dry THF (5 mL) under argon. The resulting
dark green solution was stirred for 1 h at –78 °C. A solution
of NFSI (0.41 g, 1.31 mmol, 1.3 equiv) in dry THF (5 mL)
was added over a period of 10 min. After addition, the
solution was stirred for 1 h and then allowed to warm to –30
°C. The reaction was quenched with 0.01 N HC1, and the
resulting solution was extracted with CH2Cl2. The combined
organic layer was dried over MgSO4, and the solvent was
removed under reduced pressure. The crude material was
purified via flash column chromatography on silica gel to
yield 4k as yellow oil (0.24 g, 77%). 1H NMR (300 MHz,
CDCl3): d = 1.25 (t, J = 7.0 Hz, 3 H), 1.41 (t, J = 7.0 Hz, 3
H), 4.05–4.19 (m, 2 H), 4.32–4.41 (m, 2 H), 7.86 (d, J = 8.5
Hz, 2 H), 8.29 (d, J = 8.6 Hz, 2 H) ppm; 13C NMR (75 MHz,
CDCl3): d = 16.3 (d, 3JPC = 15.0 Hz), 65.3 (d, 2JPC = 7.2 Hz),
66.2 (d, 2JPC = 7.1 Hz), 105.6 (dd, 1JPC = 193.4 Hz,
1JFC = 259.1 Hz), 123.4, 127.5 (d, 3JPC = 8.4 Hz), 142.5 (d,
2JPC = 21.0 Hz), 148.7 ppm. 31P NMR (121.5 MHz, CDCl3):
d = 5.13 (d, 2JPF = 88.1 Hz) ppm.
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(14) We thank one of the reviewers for pointing out these
possibilities.
Synlett 2009, No. 13, 2180–2182 © Thieme Stuttgart · New York