Formation of chiral α-monofluorinated-β-amino esters through organocatalytic asymmetric reduction of α-fluoro-β-enamino esters by trichlorosilane

Article abstract of DOI:10.1002/cjoc.201201067

A concise method was developed to prepare chiral α-monofluorinated- β-amino esters through N-sulfinyl urea catalyzed asymmetric hydrosilylation of α-fluoro-β-enamino esters, which affords high yields, good to high diastereoselectivities (up to>99/1), and moderate to good enantioselectivities (up to 83% ee).

Full text of DOI:10.1002/cjoc.201201067

FULL PAPER
DOI: 10.1002/cjoc.201201067
Formation of Chiral α-Monofluorinated-β-amino Esters through
Organocatalytic Asymmetric Reduction of α-Fluoro-β-enamino
Esters by Trichlorosilane
Zhang, Peng(张鹏)
Wang, Chao*(王超)
Zhou, Li(周莉)
Sun, Jian*(孙健)
Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan
610041, China
A concise method was developed to prepare chiral α-monofluorinated-β-amino esters through N-sulfinyl urea
catalyzed asymmetric hydrosilylation of α-fluoro-β-enamino esters, which affords high yields, good to high di-
astereoselectivities (up to＞99/1), and moderate to good enantioselectivities (up to 83% ee).
Keywords asymmetric reduction, sulfinyl urea, α-fluorinated-β-amino ester, stereoselectivity
Introduction
esters via asymmetric reduction of α-fluoro-β-enamino
esters.
Due to the special properties of fluorine atom(s), in-
cluding small steric size, high electronegativity and
carbon-fluorine bond strength, the introduction of fluo-
rine atom(s) into β-amino acids normally leads to re-
markable changes of their physical, chemical, and bio-
logical properties.[1] For instance, the replacement of
CH2 with CF2 in the β-amino acid fragment of
Rhodopeptins, a family of cyclic tetrapeptides isolated
from Rhodococcus species MerN1033, remarkably im-
proved the toxicity profile of the compounds.[2]
The preparation of fluorinated β-amino acids has re-
cently drawn a great deal of attentions in medicinal and
bioorganic chemistry community. Abell presented the
first example of preparing α-fluorinated-β-amino acids
using Evan’s chiral oxazolidinone auxiliary for asym-
metric induction in the key fluorination step.[3] Later,
Togni,[4] Shibata,[5] Sodeoka[6] and others presented a
number of methods to construct α-fluorinated carbonyl
compounds as the key intermediates for the synthesis of
α-fluorinated-β-amino acids via transition metal cata-
lyzed and organocatalytic asymmetric C—F bond for-
mation.[7] Lu[8] and Tan[9] also reported a method utiliz-
ing catalytic asymmetric nucleophilic addition of fluori-
nated ketoesters to access α-fluorinated-β-amino esters.
In principle, catalytic asymmetric reduction of α-fluor-
inated-β-enamino ester 1 should be an alternative
straightforward pathway to construct chiral α-fluor-
inated-β-amino ester 2 (Scheme 1). However, to the best
of our knowledge, so far no method has been reported to
implement this transformation. This stimulated our
strong interest to prepare chiral α-fluorinated-β-amino
Scheme 1 Asymmetric organocatalytic reduction of α-fluoro-β-
enamino ester 1 by trichlorosilane
R2
R2
NH
O
NH
O
HSiCl3
*
*
OR3
R1
R1
OR3
Organocatalyst
F
F
1
2
In recent years, others and we have developed Lewis
base catalyzed asymmetric reduction by trichlorosilane
(HSiCl3) into a viable asymmetric synthetic meth-
od.[10-12] Besides the reduction of imines and ketones for
the synthesis of chiral amines and alcohols, this method
has also proven to be highly effective for the reduction
of some functionalized enamines[11] such as β-enamino
esters, which affords chiral β-amino esters in high yields
and excellent stereoselectivities.[11b-11e] Recently, we
proceeded to explore if this method could also be appli-
cable for the asymmetric reduction of α-fluorinated-β-
enamino esters for the production of chiral α-fluor-
inated-β-amino esters. Herein, we wish to report our
finding that good results could be obtained for the re-
duction of a broad range of α-fluorinated-β-enamino
esters by this method when a special type of sulfinyl
ureas was used as catalyst.
Results and Discussion
We began our studies by screening different types of
Lewis base catalysts we previously developed for the
*
E-mail: wangchao@cib.ac.cn; sunjian@cib.ac.cn; Fax: 0086-028-85222753
Received October 31, 2012; accepted November 6, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201201067 or from the author.
2636
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Formation of Chiral α-Monofluorinated-β-amino Esters through Organocatalytic Asymmetric Reduction
asymmetric reduction by trichlorosilane. α-Fluoro-β-
enamino ester 1a was used as the testing substrate. The
sulfinyl ureas 3a and 3b, a special type of catalysts we
recently demonstrated to be highly efficient bifunctional
activator for the reduction of β-enamino nitro com-
pounds by HSiCl3,[12] were found to exhibit good reac-
tivity and diastereoselectivity (Table 1, Entries 2—3).[13]
But unfortunately, they displayed poor enantioselectiv-
ity. Nonetheless, we felt that this type of catalysts, if
appropriately modified, might have potentials to furnish
good enantioselectivity. We speculated that replacement
of the simple aryl R group with a sterically more hin-
dered scaffold with additional chiral elements might be
a solution to the low enantioselectivity problem with
catalyst 3. Thus, we prepared a set of catalysts 4[14]
bearing different substituents derived from (1S,2R)-
indanol and tested their efficacies in the reduction of 1a.
Their diastereomers 5 and 6 were also prepared and
tested for comparisons (Figure 1).
almost unaffected diastereoselectivity, but afforded sub-
stantially decreased enantioselectivity with reversed
sense of chirality (Entry 10), suggesting that the stereo-
chemical match between the chiral sulfinyl group and
the indanol moiety is crucial for the enantiocontrol.
Table 1 Asymmetric reduction of α-fluoro-β-enamino ester 1a
catalyzed by N-sulfinyl ureasa
PMP
PMP
NH
*
O
NH
O
HSiCl3, cat.
*
Ph
OEt
Additive
-40 ℃
Ph
OEt
F
2a
F
1a
Entry Catalyst Additive Solvent Yieldc/% drd
eed
1
2
—
3a
3b
4a
4b
4c
4d
4e
5
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
AcOH
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
＜5
88
70
88
73
93
90
95
90
95
78
94
82
70
40
70
80
85
—
—
72/28 ＜10
70/30 ＜10
86/14 14
91/9 ＜10
93/7 ＜10
3
4
O
S
O
5
R
N
N
O
S
O
H
H
6
3a R = 4-BrPh
3b R = 2-Naphthyl
N
N
H
7
95/5
95/5
95/5
58
78
71
H
OR
8
4
4a R = H
9
4b R = CH3
4c R = Bn
4d R = TBS
4e R = TBDPS
O
S
O
10
11
12
13
14
15
16
17
18
6
90/10 －30e
93/7 73
90/10 63
91/9 72
89/11 40
95/5 69
51/49 60
93/7 76
61/39 72
N
H
N
H
5
4e
4e
4e
4e
4e
4e
4e
4e
OTBDPS
PhCO2H toluene
EtOH
—
toluene
toluene
CH2Cl2
MeCN
xylene
EA
O
S
O
N
H
N
H
H2O
H2O
H2O
H2O
OTBS
6
Figure 1 Catalyst structures.
a Unless stated otherwise, reactions were carried out on a 0.05
mmol scale with HSiCl3 (3.0 equiv.) and additive (1.0 equiv.) in
solvent (0.5 mL) at －40 ℃ for 48 h. b Catalyst loading based
on α-fluoro-β-enamino ester. c Isolated yield. d The ee and dr val-
ues were determined using chiral HPLC, dr＝anti/syn. The op-
posite enantiomer was formed.
As shown in Table 1, catalysts 4a bearing a free hy-
droxyl group only gave slightly better results than cata-
lysts 3 (Entry 4). The enantioselectivity is still very low.
Either methylation (4b) or benzylation (4c) of the hy-
droxyl group had no beneficial effects on the enantiose-
lectivity (Entries 5 and 6), but enhanced both the reac-
tivity and the diastereoselectivity to a high level. Inter-
estingly, when the hydroxyl group was protected with a
bulkier TBS group (4d), the enantioselectivity was sig-
nificantly improved and 58% ee value was obtained
(Entry 7), meanwhile, the high reactivity and diastereo-
selectivity were still retained. Switch of the bulky pro-
tection group from TBS to TBDPS (4e) resulted in fur-
ther improvement of the enantioselectivity, bringing the
ee value up to 78% (Entry 8). The stereochemistry on
the 2-position of the indanol scaffold had only marginal
effects on the efficiency. Catalyst 5 derived from
(1S,2S)-indanol afforded only slightly lower enantiose-
lectivity than 4e (Entry 9). Notably, when the configu-
ration of the sulfur atom in the sulfinyl group of 4d was
changed from R to S, the resulting catalyst 6 exhibited
e
With these results in hand, we next selected catalyst
4e with the best overall performance for further optimi-
zations. As we previously observed in the reduction of
other enamine type substrates,[11a,11b] protonic additive is
important for the reactivity and stereoselectivity, and
water is superior to other additives such as acetic acid,
benzoic acid, and ethanol (Entries 11—14). Other sol-
vents such as dichloromethane, acetonitrile, xylene, and
ethyl acetate were all found to be inferior to toluene.
Finally, the substrate scope of the 4e-catalyzed re-
duction was examined. A broad range of α-fluoro-β-
enamino esters were reduced in the presence of 20
mol% 4e under optimal conditions. The results are
summarized in Table 2. In general, all the reductions
Chin. J. Chem. 2012, 30, 2636—2640
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Zhang et al.
FULL PAPER
proceeded smoothly to completion in 48 h and the de-
sired products were obtained in excellent yields, good to
high diastereoselectivities, and moderate to good enan-
tioselectivities. N-PMP amine derived substrates with
R1 as an electron-rich aryl group (1a—1e and 1i) gener-
ally gave good overall results (Entries 1—5 and 9). In
particular, up to 94% yield, ＞99/1 dr and 83% ee were
obtained for 1b bearing PMP as R1 (Entry 2). Substrates
with a relatively electron-deficient aromatic R1 group
(1f—1h) afforded slightly lower diastereoselectivities
and significantly decreased enantioselectivities (Entries
6—8). Further decreased enantioselectivity was ob-
served for substrate 1j with R1 as an aliphatic methyl
group (Entry 10). When R2 was changed from PMP to
less electronic-efficient aromatic groups such as
para-fluorophenyl (1k) and phenyl (1l) or to aliphatic
group such as benzyl (1m), only moderate enantioselec-
tivites were achieved (Entries 11—13). Notably, al-
though no substrate could afford enantioselectivity up to
a high level (＞90% ee), a single recrystallization of the
product 2a proved to be able to enrich the enantiomer to
achieve excellent enantiopurity (98% ee, Entry 1),
which further demonstrates the potential practical use-
fulness of the present catalytic reaction system.
Conclusions
In conclusion, the asymmetric reduction of α-fluoro-
β-enamino esters was successfully implemented using
chiral N-sulfinyl ureas as catalyst and trichlorosilane as
reducing agent. A broad range of α-fluoro-β-enamino
esters were reduced to afford chiral α-fluoro-β-amino
esters with high yields, good to high diastereoselectivi-
ties, and moderate to good enantioselectivities. This
method provides an alternative straightforward ap-
proach to construct chiral α-fluoro-β-amino esters.
Experimental
General procedure for the synthesis of catalysts
Catalysts 3—6 were synthesized according to the
literature procedures.[14] To a stirred solution of butane-
sulfinamide (1.0 equiv.) in anhydrous THF was added
butyllithium (1.1 equiv.) dropwise at －78 ℃. The
solution was stirred for 20 min and was then warmed to
room temperature, followed by introduction of isocy-
anate (1.1 equiv.). Water was added to quench the reac-
tion when completion. The resulting mixture was ex-
tracted with EtOAc. The combined organic phase was
washed with brine, dried over anhydrous MgSO4, and
concentrated under vacuum. The residue was purified
on silica gel with column chromatography to afford pure
product.
Table 2 Asymmetric reduction of various α-fluoro-β-enamino
esters 1 catalyzed by 4ea
R2
R2
NH
O
4e (20%)
NH
*
O
R1
R1
(R)-N-((1S,2R)-2-(tert-Butyldiphenylsilyloxy)-2,3-di-
hydro-1H-inden-1-ylcarbamoyl)-2-methylpropane-
2-sulfinamide (4e)
OEt
HSiCl3
*
OEt
F
F
1
2
White solid. 1H NMR (600 MHz, CDCl3) δ: 7.56 (d,
J＝6.7 Hz, 2H), 7.47 (d, J＝7.1 Hz, 2H), 7.26—7.37 (m,
7H), 7.13—7.14 (m, 2H), 6.99 (s, 1H), 6.19 (t, J＝11.5
Hz, 1H), 5.15 (t, J＝11.8 Hz, 1H), 4.63 (s, 1H), 2.73 (d,
J＝16.0 Hz, 1H), 2.67 (d, J＝16.3 Hz, 1H), 1.17 (s, 9H),
0.97 (s, 9H). 13C NMR (150 MHz, CDCl3) δ: 155.1,
141.2, 139.5, 135.7, 133.5, 132.9, 130.0, 129.9, 128.1,
127.9, 127.7, 127.0, 125.1, 124.8, 75.3, 58.1, 57.2, 39.7,
27.0, 22.3, 19.3; ESI HRMS calcd for (C30H38N-
NaO3SSi)＋ 557.2265, found 557.2258.
Entry R1
R2
1 Yieldb/% drc
eec
78
(98)d
1
2
Ph
PMP
PMP
PMP
1a
95
95/5
1b
1c
1d
1e
1f
94
96
96
89
92
90
92
95
97
91
92
86
＞99/1 83
3e m-MeOC6H4 PMP
4e p-CH3C6H4
97/3
97/3
72
79
71
38
61
55
70
22
56
50
48
PMP
PMP
PMP
PMP
PMP
PMP
PMP
p-FC6H4
Ph
5
6
7
8
9
p-BrC6H4
p-FC6H4
94/6
86/14
94/6
p-ClC6H4h
p-CF3C6H4
2-naphthyl
1g
1h
1i
91/9
General procedural for the reduction of 1
90/10
88/12
78/22
94/6
Under an argon atmosphere, trichlorosilane (0.15
mmol) was added dropwise to a stirred solution of 1
(0.05 mmol), catalyst 4e (0.01 mmol), and water (0.05
mmol) in anhydrous toluene (0.35 mL) at －40 ℃. The
mixture was stirred for 48 h at the same temperature.
The reaction was then quenched with a saturated aque-
ous solution of NaHCO3 and extracted with EtOAc. The
combined organic phase was washed with brine, dried
over anhydrous MgSO4, and concentrated under vac-
uum. The crude product was purified by column chro-
matography (silica gel, hexane) to afford pure products
2.
10e Me
11 Ph
12 Ph
13 Ph
1j
1k
1l
Bn
1m
85/15
a Reactions were carried out on a 0.05 mmol scale with HSiCl3
(3.0 equiv.) in toluene (0.5 mL) at －40 ℃ for 48 h. b Isolated
yield. c The ee and dr values were determined by HPLC. d Data in
parentheses was obtained after a single recrystallization in
iPrOH/hexane. e Due to the difficulty of enantiomeric separation
by HPLC, the ester product was reduced to the corresponding
alcohol for ee value measurement.
2638
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Chin. J. Chem. 2012, 30, 2636—2640

Formation of Chiral α-Monofluorinated-β-amino Esters through Organocatalytic Asymmetric Reduction
Ethyl-2-fluoro-3-(4-methoxypheny-lamino)-3-phenyl-
propanoate (2a)
Ethyl-3-(4-chlorophenyl)-2-fluoro-3-(4-methoxyphe-
nylamino)propanoate (2g)
1
1
Yellowish oil. H NMR (600 MHz, CDCl3) δ: 7.23
White solid. H NMR (600 MHz, CDCl3) δ: 7.17—
(s, 4H), 6.15 (d, J＝8.9 Hz, 2H), 6.44 (d, J＝8.9 Hz,
2H), 5.05 (dd, J＝47.8, 2.6 Hz, 1H), 4.83 (d, J＝26.5
Hz, 1H), 4.32 (s, 1H), 4.13—4.18 (m, 2H), 3.62 (s, 3H),
1.15 (t, J＝7.3 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ:
167.5 (d, J＝24.2 Hz), 152.8, 139.6, 136.6, 133.9, 128.9,
128.5, 115.4, 114.9, 91.1 (d, J＝191.2 Hz), 62.0, 59.1 (d,
J＝19.1 Hz), 55.6, 14.1. ESI calcd for (C18H19ClF-
NNaO3)＋ 374.0930, found 374.0923.
7.30 (m, 5H ), 6.62 (d, J＝9.2 Hz, 2H), 6.47 (d, J＝8.8
Hz, 2H), 5.06 (d, J＝47.3 Hz, 1H), 4.86 (d, J＝26.5 Hz,
1H), 4.34 (s, 1H), 4.12—4.17 (m, 2H), 3.61 (s, 3H),
1.15 (t, J＝7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ:
167.8 (d, J＝24.4 Hz), 152.7, 140.1, 138.0, 128.8, 128.0,
127.1, 115.4, 114.8, 92.0 (d, J＝191.4 Hz), 61.9, 59.8 (d,
J ＝ 19.0 Hz), 55.7, 14.1. ESI HRMS calcd for
(C18H20FNNaO3)＋ 340.1319, found 340.1315.
Ethyl-2-fluoro-3-(4-methoxyphenyl-amino)-3-(4-(tri-
fluoromethyl)phenyl)propanoate (2h)
Ethyl-2-fluoro-3-(4-methoxyphenyl)-3-(4-methoxy-
phenyl-amino)propanoate (2b)
White solid. 1H NMR (600 MHz, CDCl3) δ: 7.51 (d,
J＝8.2 Hz, 2H), 7.42 (d, J＝8.0 Hz, 2H), 6.60 (d, J＝
8.9 Hz, 2H), 6.43 (d, J＝8.9 Hz, 2H), 5.05 (dd, J＝47.4,
2.6 Hz, 1H), 4.90 (d, J＝26.8 Hz, 1H), 4.35 (s, 1H),
4.13—4.17 (m, 2H), 3.59 (s, 3H), 1.14 (t, J＝7.3 Hz,
3H). 13C NMR (150 MHz, CDCl3) δ: 167.4 (d, J＝24.4
Hz), 152.9, 142.2, 139.5, 130.3 (q, J＝32.3 Hz), 127.5,
125.7, 123.0 (q, J＝270.5 Hz), 115.3, 114.9, 90.5 (d,
J＝191.2 Hz), 62.1, 59.4 (d, J＝18.9 Hz), 55.6, 14.0.
ESI HRMS calcd for (C19H19F4NNaO3)＋ 408.1193,
found 408.1191.
Colorless oil. 1H NMR (600 MHz, CDCl3) δ: 7.20 (d,
J＝8.3 Hz, 2H), 6.78 (d, J＝8.4 Hz, 2H), 6.61 (d, J＝
8.4 Hz, 2H), 6.45 (d, J＝8.4 Hz, 2H), 5.00 (d, J＝47.7
Hz, 1H), 4.80 (d, J＝26.5 Hz, 1H), 4.13—4.15 (m, 2H),
3.69 (s, 3H), 3.61 (s, 3H), 1.15 (t, J＝7.3 Hz, 3H). 13C
NMR (150 MHz, CDCl3) δ: 167 (d, J＝24.4 Hz), 158.2,
151.6, 139.0, 128.8, 127.1, 114.3, 113.7, 113.1, 91.1 (d,
J＝191.2 Hz), 60.78, 58.2 (d, J＝19.3 Hz), 54.5, 54.1,
13.0. ESI HRMS calcd for (C19H22NNaO4)＋ 370.1425,
found 370.1416.
Ethyl 2-fluoro-3-(4-methoxyphenyl-amino)-3-p-tolyl-
propanoate (2d)[15]
Ethyl-2-fluoro-3-(4-methoxyphenyl-amino)-3-(-2-
naphthalenyl)propanoate (2i)
1
White oil. H NMR (600 MHz, CDCl3) δ: 7.25 (d,
1
White solid. H NMR (600 MHz, CDCl3) δ: 7.71—
J＝7.9 Hz, 2H), 7.15 (d, J＝7.9 Hz, 2H), 6.7 (d, J＝7.9
Hz, 2H), 6.55 (d, J＝7.9 Hz, 2H), 5.10 (dd, J＝47.6, 2.7
Hz, 1H), 4.89 (d, J＝26.9 Hz, 1H), 4.21—4.25 (m, 2H),
7.75 (m, 4H), 7.37—7.42 (m, 3H), 6.60 (d, J＝8.9 Hz,
2H), 6.51 (d, J＝8.9 Hz, 2H), 5.11 (dd, J＝47.2, 2.7 Hz,
1H), 5.02 (d, J＝26.4 Hz, 1H), 4.5 (s, 1H), 4.13—4.17
(m, 2H), 1.13 (t, J＝7.2 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ: 167.8 (d, J＝18.9 Hz), 152.7, 140.1, 135.6,
133.3, 133.1, 128.6, 127.9, 127.7, 126.4, 126.3, 126.2,
115.4, 114.8, 91.5 (d, J＝192.1 Hz), 61.9, 60.0 (d, J＝
18.9 Hz), 55.7, 14.1. ESI HRMS calcd for (C22H22FN-
NaO3)＋ 390.1476, found 390.1474.
3.69 (s, 3H), 2.32 (s, 2.95), 1.23 (t, J＝7.1 Hz, 3H). 13
C
NMR (150 MHz, CDCl3) δ: 168 (d, J＝23.8 Hz), 152.6,
140.2, 137.7, 134.9, 129.4, 126.9, 115.4, 114.8, 91.0 (d,
J＝191.1 Hz), 61.9, 59.5 (d, J＝19.0), 55.7, 21.1, 14.1.
Ethyl-3-(4-bromophenyl)-2-fluoro-3-(4-methoxyphe-
nyl-amino)propanoate (2e)
1
White oil. H NMR (600 MHz, CDCl3) δ: 7.38 (d,
Ethyl-2-fluoro-3-(4-fluorophenyl-amino)-3-phenyl-
propanoate (2j)
J＝8.4 Hz, 2H), 7.18 (d, J＝8.4 Hz, 2H), 6.61 (d, J＝
10.5 Hz, 2H), 6.43 (d, J＝8.9 Hz, 2H), 5.01 (dd, J＝
47.5, 2.7 Hz, 1H), 4.90 (d, J＝26.8 Hz, 1H), 4.32 (s,
1H), 4.13—4.16 (m, 2H), 3.61 (s, 3H), 1.15 (t, J＝7.8
Hz, 3H). ESI HRMS calcd for (C18H19FBrNNaO3)＋
418.0425, found 418.0415.
Yellowish oil. 1H NMR (600 MHz, CDCl3) δ:
7.18—7.30 (m, 5H), 6.71—6.74 (m, 2H), 6.42—6.45
(m, 2H), 5.10 (dd, J＝47.4, 2.52 Hz, 1H), 4.86 (d, J＝
26.6 Hz, 1H), 4.48 (s, 1H), 4.14—4.17 (m, 2H), 1.15 (t,
J＝7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ: 167.7
(d, J＝24.4 Hz), 156.0 (d, J＝287.0 Hz), 142.3, 137.6,
128.8, 128.2, 127.0, 115.7 (d, J＝22.4 Hz), 114.9 (d,
J＝7.5 Hz), 91.0 (d, J＝191.2 Hz), 62.0, 59.5 (d, J＝
19.0 Hz), 14.1. ESI HRMS calcd for (C17H17F2NNaO2)＋
328.1120, found 328.1120.
Ethyl-2-fluoro-3-(4-fluorophenyl)-3-(4-methoxyphe-
nyl-amino)propanoate (2f)
1
Yellowish oil. H NMR (600 MHz, CDCl3) δ: 7.26
—7.28 (m, 2H), 6.94—6.97 (m, 2H), 6.62 (d, J＝8.9 Hz,
2H), 6.45 (d, J＝8.9 Hz, 2H), 5.0 (dd, J＝47.5, 2.7 Hz,
1H), 4.86 (dd, J＝26.3, 2.3 Hz, 1H), 4.13—4.17 (m,
2H), 3.62 (s, 3H), 1.16 (t, J＝7.2 Hz, 3H). 13C NMR
(150 MHz, CDCl3) δ: 167.6 (d, J＝24.2 Hz), 162 (d,
J＝246.0 Hz), 152.8, 139.8, 133.7, 128.7, 115.7 (d, J＝
21.4 Hz), 115.3, 114.8, 91 (d, J＝191.4 Hz), 61.9, 59.1
(d, J＝19.1 Hz), 55.7, 14.1. ESI HRMS calcd for
(C18H19F2NNaO3)＋ 358.1225, found 358.1242.
Ethyl-2-fluoro-3-phenyl-3-(phenylamino)propanoate
(2k)
1
White solid. H NMR (600 MHz, CDCl3) δ: 7.26—
7.40 (m, 5H), 7.10—7.13 (m, 2H), 6.68—6.71 (m, 1H),
6.59 (d, J＝7.9 Hz, 2H), 5.2 (dd, J＝47.4, 2.5 Hz, 1H),
5.04 (d, J＝27.0 Hz, 1H), 4.67 (s, 1H), 4.20—4.26 (m,
2H), 1.22 (t, J＝7.1 Hz, 3H). 13C NMR (150 MHz,
Chin. J. Chem. 2012, 30, 2636—2640
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2639

Zhang et al.
FULL PAPER
Chim. Acta 2007, 90, 2251; (l) Reddy, D. S.; Shibata, N.; Nagai, J.;
Nakamura, S.; Toru, T.; Kanemasa, S. Angew. Chem., Int. Ed. 2008,
47, 164.
CDCl3) δ: 167.8, 146.0, 137.8, 129.2, 128.8, 128.0,
127.0, 118.4, 113.9, 92.3 (d, J＝192.0 Hz), 62.0, 58.75
(d, J＝19.0 Hz), 14.1. ESI HRMS calcd for (C17H18F-
NNaO2)＋ 310.214, found 320.1215.
[8] Han, X.; Kwiatkowski, J.; Xue, F.; Huang, K.-W.; Lu, Y. Angew.
Chem., Int. Ed. 2009, 48, 7604.
[9] Jiang, Z.; Pan, Y.; Zhao, Y.; Ma, T.; Lee, R.; Yang, Y.; Huang,
K.-W.; Wong, M. W.; Tan, C.-H. Angew. Chem., Int. Ed. 2009, 48,
3627.
Acknowledgement
We are grateful for financial supports from the Na-
tional Natural Science Foundation of China (Project
Nos. 20972151, 21272227 and 91013006).
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(Pan, B.; Lu, Z.)
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