Enantioselective fluorination of α-chloro-β-keto phosphonates in the presence of chiral palladium complexes

Article abstract of DOI:10.1016/j.tetlet.2013.04.054

The catalytic enantioselective electrophilic fluorination of α-chloro-β-keto phosphonates promoted by chiral palladium complexes has been developed, allowing facile synthesis of the corresponding α-chloro-α-fluoro-β-keto phosphonates with excellent enanti

Full text of DOI:10.1016/j.tetlet.2013.04.054

Tetrahedron Letters 54 (2013) 3359–3362
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Enantioselective fluorination of a-chloro-b-keto phosphonates
in the presence of chiral palladium complexes
⇑
Saet Byeol Woo, Chang Won Suh, Kwang Oh Koh, Dae Young Kim
Department of Chemistry, Soonchunhyang University, Asan, Chungnam 336-745, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic enantioselective electrophilic fluorination of
chiral palladium complexes has been developed, allowing facile synthesis of the corresponding
chloro- -fluoro-b-keto phosphonates with excellent enantioselectivity (up to 95% ee).
a-chloro-b-keto phosphonates promoted by
Received 18 February 2013
Revised 15 April 2013
Accepted 15 April 2013
Available online 24 April 2013
a
-
a
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric catalysis
Chiral palladium catalysts
Electrophilic fluorination
a-Chloro-b-keto phosphonates
Organofluorine compounds are of central importance in the
The chiral gem-chlorofluoromethylene group would be syn-
thetic intermediates in asymmetric synthesis for various chiral
fluorinated compounds and as a chiral isostere of the difluoro-
methylene group in biologically active compounds. A few synthetic
pharmaceutical and agrochemical industries because the replace-
ment of a hydrogen with a fluorine atom in biologically active mol-
ecules can be beneficial in terms of physicochemical properties and
biological activities.1 Chiral organofluorine compounds containing
a fluorine atom bonded directly to a stereogenic center have been
utilized in studies of enzyme mechanisms and as building block for
bioactive compounds.2 The application of chiral organofluorine
compounds is restricted by the limited availability of effective syn-
thetic methods for the enantioselective construction of fluorinated
quaternary carbon centers. Thus, the development of asymmetric
C–F bond formation process has become an important area in or-
ganic synthesis.3 To date, there are a great number of reports on
the asymmetric synthesis of organofluorine compounds containing
a fluorine atom bonded directly to a stereogenic center.4 Among
the various procedures to produce the enantiopure organofluorine
compounds, catalytic enantioseletive fluorinations provide one of
the most efficient synthetic methods. Since the first catalytic enan-
tioseletive fluorination reported by Togni and Hintermann in
2000,5 a number of catalyst systems for the enantioselective elec-
trophilic fluorination of active methane compounds have been re-
ported.6–9 Recently, several groups have reported catalytic
enantioselective fluorination of active methine derivatives using
chiral metal complexes such as Binap–Pd(II) and transition me-
tal–bis(oxazoline) complexes and organocatalysts such as cincho-
nine-derived quaternary ammonium salt, imidazolidinone, and
proline derivatives.6–9
methods for the preparation of chiral
ters are reported.10 Recently, Shibatomi et al. have reported the
first catalytic enantioselective synthesis of -chloro- -fluoro-b-
a-chloro-a-fluoro-b-keto es-
a
a
keto phosphonates using 10 mol % of Cu(II) complex of a chiral
spiro oxazoline ligand.11 There are still some drawbacks to the pre-
viously reported procedure, such as the high catalyst loading and
anhydrous reaction conditions required for the high enantioselec-
tivity. Accordingly, the development of alternative catalysts for
the catalytic enantioselective electrophilic fluorination of
a-
chloro-b-keto phosphonates is highly desirable.
As part of research program related to the development of syn-
thetic methods for the enantioselective construction of stereogenic
carbon centers,12 we recently reported the catalytic enantioselec-
tive functionalization of active methines in the presence of chiral
palladium(II) complexes.13 In this Letter, we wish to report the cat-
alytic enantioseletive electrophilic
a-fluorination of a-chloro-b-
keto phosphonates using air- and moisture-stable chiral palladium
complexes 1 (Fig. 1)14 under practical conditions at low catalyst
loadings (as low as 0.5 mol %) with excellent enantiocontrol.
To determine suitable reaction conditions for the catalytic
enantioselective fluorination of
we initially investigated the reaction system with
a
-chloro-b-keto phosphonates,
-chloro-b-keto
a
phosphonates 2 and N-fluorobenzenesulfonimide (3, NFSI) in the
presence of 10 mol % of chiral palladium(II) catalyst in methanol
at room temperature. We first examined the impact of the chiral
diphosphine ligands in catalysts 1 (Table 1, entries 1–8). By screen-
⇑
Corresponding author. Tel.: +82 41 530 1244; fax: +82 41 530 1247.
E-mail address: dyoung@sch.ac.kr (D.Y. Kim).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.054

3360
S. B. Woo et al. / Tetrahedron Letters 54 (2013) 3359–3362
To examine the generality of the catalytic enantioselective
fluorination of -chloro-b-keto phosphonates 2 by using chiral
palladium(II) complex 1f, we studied the fluorination of
2+
1a : Ar = Ph, X = BF4
1b : Ar = Ph, X = OTf
a
PAr2
Pd
PAr2
1c : Ar = Ph, X = SbF6
OH2
a-
-
1d : Ar = 4-MeC6H4, X = OTf
1e : Ar = 3,5-Me2C6H3, X = BF4
1f : Ar = 3,5-Me2C6H3, X = OTf
1g : Ar = 3,5-Me2C6H3, X = SbF6
2X
chloro-b-keto phosphonates 2 with N-fluorobenzenesulfonimide
NCMe
(3, NFSI).15 As seen from the results summarized in Table 2, the
corresponding
tained in moderate to high yields with excellent enantioselectivi-
ties. The fluorination reaction of dimethyl -chloro-b-keto
a-chloro-a-fluoro-b-keto phosphonates 4 were ob-
Figure 1. Structures of chiral palladium complexes 1.
a
phosphonate 2b proceeded to afford the fluorinated product 4b
with high selectivity under the optimized reaction conditions
(89% ee, Table 2, entry 2). A range of electron-donating and elec-
ing chiral palladium(II) complexes 1a–g, we found that catalyst 1f
was the best catalyst for this enantioselective electrophilic fluori-
nation, affording the corresponding product 4a with 91% ee at
room temperature (Table 1, entry 6). Concerning the solvent, the
use of protic polar solvents such as MeOH and EtOH gave the best
results (Table 1, entries 6 and 8), whereas the fluorination in
i-PrOH, CF3CH2OH, THF, acetone, dichloromethane, toluene,
trifluorotoluene, and hexafluorobenzene led to slightly lower
enantioselectivities (entries 9–16). In the presence of 2,6-di-t-bu-
tyl-4-methyl pyridine as base, the reaction proceeded rapidly
without significant change of enantioselectivity (entries 17–21).
Bulky organic base such as 2,6-di-t-butyl-4-methyl pyridine
(DTBMP) is appropriate to accelerate the reaction without coordi-
nation to metal complexes. The present catalytic system tolerates
catalyst loading down to 5, 1, 0.5, or 0.1 mol % without compromis-
ing the enantioselectivity (Table 1, entries 17–20). The absolute
configuration of 4 was established by comparison of the optical
rotation and chiral HPLC analysis with previously reported
values.11
tron-withdrawing substitutions on the b-aryl ring of the
a-
chloro-b-keto phosphonates 2 provided reaction products in high
yields and excellent enantioselectivities (83–95% ee, Table 2, en-
tries 3–8). The heteroaryl-, naphthyl-, and alkyl-substituted
a-chloro-b-keto phosphonates 2i–2k provided the products 4i–
4k with high selectivity (85–95% ee, Table 2, entries 9–11).
The present method is operationally simple and efficient and,
thus, may be valuable for practical chemical synthesis. As shown
in Scheme 1, when
with NFSI under the optimal reaction conditions, the reaction pro-
ceeded smoothly to afford the desired -chloro- -fluoro-b-keto
a-chloro-b-keto phosphonates 2a was treated
a
a
phosphonates 4a at the gram scale with 81% yield and 91% ee
(Scheme 1).
On the basis of our results, a plausible mechanism of the cata-
lytic cycle is outlined Scheme 1. The Pd(II) complex activates the
substrate through coordination of the
nates 2, and DTBMP as Brønsted base abstracts an acidic
a
-chloro-b-keto phospho-
-proton
a
of phosphonates, affording the complex 5. Chiral Pd-coordinated
nucleophile 5 reacts with NFSI to produce the fluorinated product
4 (Scheme 2).
Table 1
Optimization of reaction conditionsa
In summary, we have accomplished the efficient catalytic enan-
tioselective electrophilic a-fluorination of various a-chloro-b-keto
O
O
O
O
phosphonates 2 with excellent enantioselectivity (up to 95% ee)
with palladium complex 1f as chiral catalyst. It should be noted
that this fluorination reaction proceeds well using air- and
moisture-stable chiral palladium complexes at low catalyst
cat. 1 (10 mol%)
solvent, rt
P(OEt)2
P(OEt)2
(PhSO2)2NF
+
Ph
Ph
F
Cl
Cl
4a
2a
3
Entry
Cat. 1
Solvent
Time (h)
Yieldb (%)
eec (%)
Table 2
Enantioselective fluorination of
a
-chloro-b-keto phosphonate 2a
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
i-PrOH
CF3CH2OH
THF
Acetone
DCM
PhMe
PhCF3
C6F6
MeOH
MeOH
MeOH
MeOH
MeOH
24
24
18
18
24
24
24
18
18
18
18
18
18
18
18
18
24
24
24
24
24
50
52
52
48
55
56
52
51
57
51
54
45
40
47
41
32
90
81
80
62
45
79
80
77
79
91
91
91
91
83
71
85
85
75
81
87
79
91
91
91
91
91
O
O
O
O
cat. 1f (0.5 mol%)
DTBMP(2.0 eq.)
MeOH, rt, 1 d
P(OR2)2
P(OR2)2
(PhSO2)2NF
R1
+
R1
F
Cl
Cl
4
2
3
10
11
12
13
14
15
16
17d,e
18d,f
19d,g
20d,h
21d,i
Entry
2, R1, R2
Yieldb (%)
eec (%)
1
2
3
2a, Ph, Et
2b, Ph, Me
4a, 80
4b, 76
4c, 75
4d, 79
4e, 88
4f, 64
4g, 83
4h, 78
4i, 40
4j, 85
4k, 56
91
89
95
91
93
91
91
83
85
95
93
2c, 4-MeC6H4, Et
2d, 4-MeOC6H4, Et
2e, 4-FC6H4, Et
2f, 4-ClC6H4, Et
2g, 4-BrC6H4, Et
2h, 4-NO2C6H4, Et
2i, 2-Thienyl, Et
2j, 2-Naphthyl, Et
2k, n-Pentyl, Et
4
5d
6
7e
8d
9e
10
11f
a
Reaction conditions: Diethyl(1-chloro-2-oxo-2-phenylethyl)phosphonate (2a,
0.3 mmol), NFSI (3, 0.33 mmol), and catalyst 1 at room temperature.
a
Reaction conditions:
a
-Chloro-b-keto phosphonate 2 (0.3 mmol), DTBMP
b
Isolated yield.
(0.6 mmol), NFSI (3, 0.33 mmol), catalyst 1f (1.5 lmol), and MeOH (1.2 mL) at room
c
Enantiopurity was determined by HPLC analysis using Chiralpak IC column.
2,6-Di-tert-butyl-4-methylpyridine (DTBMP, 2.0 equiv) was added as base.
5 mol % catalyst loading.
1 mol % catalyst loading.
0.5 mol % catalyst loading.
0.1 mol % catalyst loading.
0.05 mol % catalyst loading.
temperature.
d
b
Isolated yield.
e
c
Enantiopurity was determined by HPLC analysis using Chiralpak IC (for 4a–4b,
4d–4h, and 4k) and AD-H (for 4c and 4i–4j) columns.
f
g
d
This reaction was conducted using 3 mol % catalyst.
This reaction was conducted using 1 mol % catalyst for 4 d.
This reaction was conducted using 3 mol % catalyst for 3 d.
h
e
i
f

S. B. Woo et al. / Tetrahedron Letters 54 (2013) 3359–3362
3361
Angew. Chem., Int. Ed. 2006, 45, 554; (d) Prakash, G. K. S.; Bier, P. Angew. Chem.,
Int. Ed. 2006, 45, 2172; (e) Hamashima, Y.; Sodeoka, M. Synlett 2006, 1467; (f)
Ma, J.-A.; Cahard, D. Chem. Rev. 2008, 108, PR1; (g) Ueda, M.; Kano, T.; Maruoka,
K. Org. Biomol. Chem. 2009, 7, 2005; (h) Lectard, S.; Hamashima, Y.; Sodeoka, M.
Adv. Synth. Catal. 2010, 352, 2708; (i) Kang, Y. K.; Kim, D. Y. Curr. Org. Chem.
2010, 14, 917; (j) Cahard, D.; Xu, X.; Couve-Bonnaire, S.; Pannecoucke, X. Chem.
Soc. Rev. 2010, 39, 558.
O
O
P(OEt)2
Ph
O
O
Cl
P(OEt)2
Ph
cat. 1f (0.5 mol%)
DTBMP(2.0 eq.)
MeOH, rt, 1.5 d
2a (1.00 g)
F
Cl
4a (0.86 g)
(81% yield, 91% ee)
5. Hintermann, L.; Togni, A. Angew. Chem., Int. Ed. 2000, 39, 4359.
+
6. For b-ketoesters: (a) Kim, D. Y.; Park, E. J. Org. Lett. 2002, 4, 545; (b)
Hamashima, Y.; Yagi, K.; Takano, H.; Tamás, L.; Sodeoka, M. J. Am. Chem. Soc.
2002, 124, 14530; (c) Hamashima, Y.; Takano, H.; Hotta, D.; Sodeoka, M. Org.
Lett. 2003, 5, 3225; (d) Ma, J.-A.; Cahard, D. Tetrahedron: Asymmetry 2004, 15,
1007; (e) Shibata, N.; Ishimaru, T.; Nagai, T.; Kohno, J.; Toru, T. Synlett 2004,
1703; (f) Shibata, N.; Kohno, J.; Takai, K.; Ishimaru, T.; Nakamura, S.; Toru, T.;
Kanemasa, S. Angew. Chem., Int. Ed. 2005, 44, 4204; (g) Cho, M. J.; Kang, Y. K.;
Lee, N. R.; Kim, D. Y. Bull. Korean Chem. Soc. 2007, 28, 2191; (h) Shibatomi, K.;
Tsuzuki, Y.; Iwasa, S. Chem. Lett. 2008, 37, 1098; (i) Wang, X.; Lan, Q.;
Shirakawa, S.; Maruoka, K. Chem. Commun. 2010, 321; (j) Deng, Q.-H.;
Wadepohl, H.; Gade, L. H. Chem. Eur. J. 2011, 17, 14922; (k) Jacquet, O.;
Clement, N. D.; Freixa, Z.; Ruiz, A.; Claver, C.; Leeuwen, P. W. N. M. Tetrahedron:
Asymmetry 2011, 22, 1490; (l) Tanzer, E.-M.; Schweizer, W. B.; Ebert, M.-O.;
(PhSO2)2NF
3 (1.19 g)
Scheme 1. Gram scale enantioselective fluorination of diethyl (1-chloro-2-oxo-2-
phenylethyl)phosphonate (2a) with NFSI (3).
*
2+
Pd
O
O
P
P
2X-
R
(EtO)2P
R
Gilmour, R. Chem. Eur. J. 2012, 18, 2006; For
a-keto ester: (m) Suzuki, S.;
Pd-cat 1
O
O
Kitamura, Y.; Lectard, S.; Hamashima, Y.; Sodeoka, M. Angew. Chem., Int. Ed.
2012, 51, 4581.
Cl
(EtO)2P
2
7. For a-cyano acetates: (a) Kim, H. R.; Kim, D. Y. Tetrahedron Lett. 2005, 46, 3115;
(b) Park, E. J.; Kim, H. R.; Joung, C. W.; Kim, D. Y. Bull. Korean Chem. Soc. 2004,
25, 1451; (c) Kim, S. M.; Kang, Y. K.; Cho, M. J.; Kim, D. Y. Bull. Korean Chem. Soc.
2007, 28, 2435.
Cl
-
HB+ N(SO2Ph)2
B (base)
8. For b-keto phosphonates: (a) Bernardi, L.; Jørgensen, K. A. Chem. Commun.
2005, 1324; (b) Hamashima, Y.; Suzuki, T.; Shimura, Y.; Shimizu, T.;
Umebayashi, N.; Tamura, T.; Sasamoto, N.; Sodeoka, M. Tetrahedron Lett.
2005, 46, 1447; (c) Kim, S. M.; Kim, H. R.; Kim, D. Y. Org. Lett. 2005, 7, 2309; (d)
Kim, S. M.; Kang, Y. K.; Lee, K.; Mang, J. Y.; Kim, D. Y. Bull. Korean Chem. Soc.
2006, 27, 423; (e) Hamashima, Y.; Suzuki, T.; Takano, H.; Shimura, Y.; Tsuchiya,
Y.; Moriya, K.; Goto, T.; Sodeoka, M. Tetrahedron 2006, 62, 7168.
+BH X-
L
P
P
+
*
*
X-
Pd
(PhO2S)2N
2+
Pd
P
P
+
X-
+
9. For
a-cyanophosphonates: (a) Kang, Y. K.; Cho, M. J.; Kim, S. M.; Kim, D. Y.
NFSI
O
O
O
O
Synlett 2007, 1135; (b) Moriyama, K.; Hamashima, Y.; Sodeoka, M. Synlett 2007,
1139.
(EtO)2P
(EtO)2P
R
R
10. (a) Frantz, R.; Hintermann, L.; Perseghini, M.; Broggini, D.; Togni, A. Org. Lett.
2003, 5, 1709; (b) Cho, M. J.; Kang, Y. K.; Lee, N. R.; Kim, D. Y. Bull. Korean Chem.
Soc. 2007, 28, 2191; (c) Shibatomi, K.; Yamamoto, H. Angew. Chem., Int. Ed.
2008, 47, 5796; (d) Kang, S. H.; Kim, D. Y. Adv. Synth. Catal. 2010, 352, 2783.
11. Shibatomi, K.; Narayama, A.; Soga, Y.; Muto, T.; Iwasa, S. Org. Lett. 2011, 13,
2944.
Cl
F
Cl
5
4
Scheme 2. Assumed catalytic cycle.
12. (a) Kim, D. Y.; Huh, S. C. Tetrahedron 2001, 57, 8933; (b) Kim, D. Y.; Huh, S. C.;
Kim, M. H. Tetrahedron Lett. 2001, 42, 6299; (c) Kim, D. Y.; Park, E. J. Org. Lett.
2002, 4, 545; (d) Park, E. J.; Kim, M. H.; Kim, D. Y. J. Org. Chem. 2004, 69, 6897;
(e) Kim, S. M.; Lee, J. H.; Kim, D. Y. Synlett 2008, 2659; (f) Jung, S. H.; Kim, D. Y.
Tetrahedron Lett. 2008, 49, 5527; (g) Kang, Y. K.; Kim, D. Y. J. Org. Chem. 2009,
74, 5734; (h) Kwon, B. K.; Kim, S. M.; Kim, D. Y. J. Fluorine Chem. 2009, 130, 759;
(i) Oh, Y. Y.; Kim, S. M.; Kim, D. Y. Tetrahedron Lett. 2009, 50, 4674; (j) Lee, J. H.;
Kim, D. Y. Adv. Synth. Catal. 2009, 351, 1779; (k) Moon, H. W.; Cho, M. J.; Kim, D.
Y. Tetrahedron Lett. 2009, 50, 4896; (l) Mang, J. Y.; Kwon, D. G.; Kim, D. Y. J.
Fluorine Chem. 2009, 130, 259; (m) Lee, J. H.; Kim, D. Y. Synthesis 2010, 1860–
1864; (n) Kang, Y. K.; Kim, S. M.; Kim, D. Y. J. Am. Chem. Soc. 2010, 132, 11847;
(o) Moon, H. W.; Kim, D. Y. Tetrahedron Lett. 2010, 51, 2906; (p) Lee, H. J.; Kang,
S. H.; Kim, D. Y. Synlett 2011, 1559; (q) Kang, Y. K.; Yoon, S. J.; Kim, D. Y. Bull.
Korean Chem. Soc. 2011, 32, 1195; (r) Yoon, S. J.; Kang, Y. K.; Kim, D. Y. Synlett
2011, 420; (s) Lee, H. J.; Woo, S. B.; Kim, D. Y. Tetrahedron Lett. 2012, 53, 3373;
(t) Lee, H. J.; Woo, S. B.; Kim, D. Y. Molecules 2012, 17, 7523; (u) Woo, S. B.; Kim,
D. Y. Beilstein J. Org. Chem. 2012, 8, 699; (v) Lee, H. J.; Kim, S. M.; Kim, D. Y.
Tetrahedron Lett. 2012, 53, 3437; (w) Moon, H. W.; Kim, D. Y. Bull. Korean Chem.
Soc. 2012, 33, 2845; (x) Kang, Y. K.; Lee, H. J.; Moon, H. W.; Kim, D. Y. RSC Adv.
2013, 3, 1332.
loadings (as low as 0.5 mol %). Current efforts are toward develop-
ing synthetic applications of this a-fluorination reaction.
Acknowledgment
This research was supported in part by the Soonchunhyang
University Research Fund.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.04
.054.
13. For recent selected examples of the enantioselective reactions catalyzed by
chiral palladium complexes in our laboratory, see: (a) Kim, S. M.; Kim, H. R.;
Kim, D. Y. Org. Lett. 2005, 7, 2309; (b) Kim, H. R.; Kim, D. Y. Tetrahedron Lett.
2005, 46, 3115; (c) Kang, Y. K.; Kim, D. Y. Tetrahedron Lett. 2006, 47, 4565; (d)
Kang, Y. K.; Cho, M. J.; Kim, S. M.; Kim, D. Y. Synlett 2007, 1135; (e) Kang, Y. K.;
Kim, D. Y. Bull. Korean Chem. Soc. 2008, 29, 2093; (f) Lee, J. H.; Bang, H. T.; Kim,
D. Y. Synlett 2008, 1821; (g) Kang, S. H.; Kang, Y. K.; Kim, D. Y. Tetrahedron 2009,
65, 5676; (h) Kang, Y. K.; Kwon, B. K.; Kim, D. Y. Tetrahedron Lett. 2011, 52,
3247; (i) Kang, Y. K.; Suh, K. H.; Kim, D. Y. Synlett 2011, 1125; (j) Kang, Y. K.;
Kim, D. Y. Tetrahedron Lett. 2011, 52, 2356; (k) Kwon, B. K.; Mang, J. Y.; Kim, D.
Y. Bull. Korean Chem. Soc. 2012, 33, 2481; (l) Kang, Y. K.; Kim, H. H.; Koh, K. O.;
Kim, D. Y. Tetrahedron Lett. 2012, 53, 3811; (m) Lee, H. J.; Kim, D. Y. Synlett
2012, 1629; (n) Lee, H. J.; Kim, D. Y. Tetrahedron Lett. 2012, 53, 6984.
14. (a) Li, K.; Hii, K. K. Chem. Commun. 2003, 1132; (b) Li, K.; Horton, P. N.;
Hursthouse, M. B.; Hii, K. K. J. Organomet. Chem. 2003, 665, 250; For an
aquapalladium complex, see: (c) Shimada, T.; Bajracharya, G. B.; Yamamoto, Y.
Eur. J. Org. Chem. 2005, 59. and references cited therein; (d) Vicente, J.; Arcas, A.
Coord. Chem. Rev. 2005, 249, 1135; For recent selected reviews for the
enantioselective reactions catalyzed by chiral palladium complexes, see: (e)
Sodeoka, M.; Hamashima, Y. Chem. Commun. 2009, 5787; (f) Smith, A. M. R.;
Hii, K. K. Chem. Rev. 2011, 111, 1637.
References and notes
1. (a) Chambers, R. D. Fluorine in Organic Chemistry; Blackwell: Oxford, 2004; (b)
Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications;
Wiley-VCH: Weinheim, 2004; (c) Hiyama, T.; Kanie, K.; Kusumoto, T.;
Morizawa, Y.; Shimizu, M. Organofluorine Compounds: Chemistry and
Applications; Springer: Berlin, 2000; For reviews: (d) Kirk, K. L. J. Fluorine
Chem. 2006, 127, 1013; (e) Isanbor, C.; O’Hagan, D. J. Fluorine Chem. 2006, 127,
303; (f) Bohm, H.-J.; Banmer, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Muller, K.;
Obst-Sander, U.; Stahl, M. ChemBioChem 2004, 5, 637.
2. (a)Asymmetric Fluoroorganic Chemistry: Synthesis, Application, and Future
Directions; ACS Symposium Series Vol. 746; Ramachandran, P. V., Ed.; American
Chemical Society: Washington, DC, 2000; (b)Enantiocontrolled Synthesis of
Fluoro-organic Compounds; Soloshonok, V. A., Ed.; John Wiley
& Sons:
Chichester, 1999; For review: (c) Bravo, P.; Resnati, G. Tetrahedron:
Asymmetry 1990, 1, 661; (d) Mikami, K.; Itoh, Y.; Yamanaka, M. Chem. Rev.
2004, 104, 1.
3. For reviews: (a) Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96, 1737; (b)
Taylor, S. D.; Kotoris, C. C.; Hum, G. Tetrahedron 1999, 55, 12431.
4. (a) Ibrahim, H.; Togni, A. Chem. Commun. 2004, 1147; (b) France, S.;
Weatherwax, A.; Lectka, T. Eur. J. Org. Chem. 2005, 475; (c) Pihko, P. M.

3362
S. B. Woo et al. / Tetrahedron Letters 54 (2013) 3359–3362
15. Typical procedure for the fluorination of diethyl(1-chloro-2-oxo-2-
phenylethyl)phosphonate (2a) with NFSI (3): To a stirred solution of diethyl(1-
chloro-2-oxo-2-phenylethyl)phosphonate (2a, 87.2 mg, 0.3 mmol) and catalyst
(S)-Diethyl(1-chloro-1-fluoro-2-oxo-2-phenylethyl)phosphonate (4a): ½a D27
ꢁ5.9
ꢀ
(c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3): d 8.16–8.14 (m, 2H), 7.66–7.61 (m,
1H), 7.52–7.48 (m, 2H), 4.48–4.27 (m, 4H), 1.41 (td, J = 7.2, 0.8 Hz, 3H), 1.38 (td,
J = 7.2, 0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 188.6 dd, J = 25.0, 7.0 Hz),
134.5, 131.8 (dd, J = 7.0, 3.0 Hz), 130.5 (d, J = 5.0 Hz), 128.6, 103.2 (dd, J = 272.0,
185.0 Hz), 65.8 (d, J = 6.0 Hz), 65.6 (d, J = 6.0 Hz), 16.4 (d, J = 6.0 Hz), 16.3 (d,
J = 5.0 Hz); the enantiomeric ratio was determined by HPLC (n-hexane/i-
PrOH = 83:17, 254 nm, 1.0 mL/min) using a Chiralpak IC column: tR = 16.2 min
(major), tR = 12.6 min (minor), 91% ee.
1f (1.8 mg, 1.5 lmol) in MeOH (1.2 mL) were added 2,6-di-tert-butyl-4-
methylpyridine (123.2 mg, 0.6 mmol) and NFSI (3, 104.1 mg, 0.33 mmol) at
room temperature. The reaction mixture was stirred for 1 day at room
temperature. After completion of the reaction, the resulting solution was
concentrated in vacuo and the obtained residue was purified by flash column
chromatography (EtOAc/hex, 1:3) to afford (S)-diethyl(1-chloro-1-fluoro-2-
oxo-2-phenylethyl)phosphonate (4a, 80% yield, 74.1 mg).