Resolution of pentafluorophenyl active esters using (S)-4-phenyloxazolidin- 2-thione

Article abstract of DOI:10.1055/s-0028-1088218

A series of structurally related racemic pentafluorophenyl active esters were resolved using an equimolar amount of (S)-4- phenyloxazolidin-2-thione. The levels of diastereocontrol were found to be excellent (>86% de at -30% conversion).

Full text of DOI:10.1055/s-0028-1088218

960
LETTER
Resolution of Pentafluorophenyl Active Esters Using (S)-4-Phenyloxazolidin-
2-thione
R
esolution of Pent
a
a
fluorophen
j
yl
A
ct
l
ive Este
a
rs Al Shaye, Tom W. Broughton, Elliot Coulbeck, Jason Eames*
Department of Chemistry, University of Hull, Cottingham Road, Kingston upon Hull, HU6 7RX, UK
Fax +44(1482)466410; E-mail: j.eames@hull.ac.uk
Received 3 December 2008
pentafluorophenyl 2-phenylpropionate [(rac)-2] and
Abstract: A series of structurally related racemic pentafluorophe-
nyl active esters were resolved using an equimolar amount of (S)-4-
phenyloxazolidin-2-thione. The levels of diastereocontrol were
found to be excellent (>86% de at ~30% conversion).
structurally related pentafluorophenyl active esters (rac)-
7, (rac)-9, (rac)-11, (rac)-13, (rac)-15, and (rac)-17, us-
ing 4-phenyloxazolidin-2-thione [(S)-4] as the resolving
agent (Scheme 2). We outline the scope and limitations of
this methodology and disclose the probable reasons for
the high levels of diastereocontrol.
Key words: chiral auxiliaries, chiral resolution, molecular recogni-
tion, stereoselectivity
We first investigated the resolution of pentafluorophenyl
2-phenylpropionate [(rac)-2] using an equimolar amount
of 4-phenyl oxazolidin-2-thione [(S)-4, Scheme 2]. Treat-
ment of 4-phenyloxazolidin-2-thione [(S)-4] with n-BuLi
in THF at –78 °C, followed by addition of pentafluo-
rophenyl 2-phenylpropionate [(rac)-2], gave after two
hours the corresponding oxazolidin-2-thione adduct
(R,S)-syn-58 in 30% yield with 88% de (Scheme 2). The
level of diastereocontrol was found to be excellent [mea-
The resolution and synthesis of pharmaceutically
important1 enantiomerically pure 2-phenylpropionic acid
and its derivatives are well documented.2 Since 2000, we
have been interested in the mutual, kinetic, and parallel
resolutions3 of pentafluorophenyl 2-phenylpropionate
(rac)-24 and related derivatives using Evans’ 4-phenylox-
azolidin-2-one [(R)-1, Scheme 1].5 Deprotonation of ox-
azolidin-2-one (R)-1 (1 equiv) with n-BuLi (1.1 equiv) at
–78 °C, followed by the addition of pentafluorophenyl 2-
phenylpropionate (rac)-2 (1 equiv), gave after 2 hours the
corresponding oxazolidin-2-one adducts (S,R)-syn-3 and
(R,R)-anti-3 in 39% and 16% yields, respectively, with a
diastereomeric ratio of 70:30 (Scheme 1).5 The level of dia-
stereocontrol was poor (40% de) due to competitive for-
mation of the minor diastereomer under these reaction
conditions. This level of diastereocontrol for (S,R)-syn-3
could be improved to 84% de using an excess of the race-
mic pentafluorophenyl 2-phenylpropionate [(rac)-2, 2
equiv, Scheme 1].5
1
sured by H NMR spectroscopy (400 MHz)].9 The re-
maining active ester 210,11 was recovered by column
chromatography in 47% yield and was found to have an S-
configuration with 42% ee (Scheme 2).12 With this infor-
mation at hand, we next investigated the diastereoselectiv-
ity of this process by altering the relative amount of the
active ester (rac)-2 (0.25–2 equiv). To our surprise, in all
cases studied, the relative diastereoselectivity remained
constant (87–90% de), whereas understandably the yields
improved with an increase of active ester (rac)-2
(Table 1). Intriguingly, the level of diastereocontrol re-
mained constant irrespective of the amount of active ester
(rac)-2 used.13
In our attempt to improve the diastereoselective outcome
of this methodology,6 we became interested in the use of
the structurally related 4-phenyloxazolidin-2-thione [(S)-
4]7 as a resolving component. We now report an extension
to our original methodology for the efficient resolution of
O
S
S
O
1. n-BuLi (1.1 equiv)
THF, –78 °C
Ph
Ph
OC6F5
HN
Ph
O
N
O
O
2.
Me
Me
O
Ph
O
O
O
O
Ph
1. n-BuLi (1.1 equiv)
THF, –78 °C
OC6F5
Ph
Ph
Me
(rac)-2
(1 equiv)
N
O
HN
Ph
O
N
O
O
2.
(S)-4
(1 equiv)
(R,S)-syn-5
(S)-2
47%; 42% ee
Me
Me
Ph
30%; 88% de
Ph
Ph
OC6F5
Me
(rac)-2
Scheme 2 Resolution of pentafluorophenyl 2-phenylpropionate
(rac)-2 using oxazolidin-2-thione (S)-4
(R)-1
(1 equiv)
(S,R)-syn-3
(R,R)-anti-3
(1 equiv)
(2 equiv)
39%
52%
70:30
92:8
16%
4%
We next chose to investigate the temperature dependence
of this resolution by the addition of a solution of lithiated
oxazolidin-2-thione derived from (rac)-4 (in THF) to a so-
lution of active ester (rac)-2 (in THF) at a variety of tem-
peratures (ranging from –88 °C to 20 °C, Table 2). The
overall levels of diastereoselectivity were found to be
highly temperature dependent; for high yield and excel-
Scheme 1 Resolution of pentafluorophenyl 2-phenylpropionate
[(rac)-2] using oxazolidin-2-one (R)-1
SYNLETT 2009, No. 6, pp 0960–0964
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088218; Art ID: D40208ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
0
9

LETTER
Resolution of Pentafluorophenyl Active Esters
961
Table 3 Variation of Time and Diastereoselectivity
Table 1 Resolution of Active Ester (S)-2 Using 4-Phenyloxazoli-
din-2-thione [(S)-4]a
Time
1 min
5 min
10 min
20 min
1 h
Yield (%) of (R,S)-syn-5
de (%)
84
Entry
Active ester (S)-2 Yield (%) of product de (%)
<5
10
15
19
26
32
37
(n equiv)
(R,S)-syn-5
86
1
2
3
4
5
0.25
0.5
1
13
33
30
40
45
88
90
88
87
88
86
86
88
1.5
2
2 h
88
a One equiv of 4-phenyloxazolidin-2-thione [(S)-4] was used.
12 h
80
In an attempt to get a better understanding of this process,
we next chose to investigate two sterically demanding ac-
tive esters, pentafluorophenyl 2-phenylbutanoate [(rac)-
7] and pentafluorophenyl 2-phenyl-3-methylbutanoate
[(rac)-9, Table 4, entries 2 and 3)]. The de was improved
to 96% [for oxazolidin-2-thione adduct (R,S)-syn-8] using
pentafluorophenyl 2-phenylbutanoate [(rac)-7, Table 4,
entry 2). In comparison, for the more sterically demanding
pentafluorophenyl 2-phenyl-3-methylbutanoate [(rac)-9],
the corresponding oxazolidin-2-thione adduct (R,S)-syn-
10 was not formed under our standard reaction conditions
(–78 °C for 2 h and 12 h, Table 4, entries 3 and 4). In con-
trast, by allowing the reaction mixture to warm up to room
temperature and stirring the resulting reaction mixture for
12 h, gave the oxazolidin-2-thione adduct (R,S)-syn-10 in
51% yield with low de (28% de, Table 4, entry 3).
lent levels of molecular recognition between the oxazoli-
din-2-thione (rac)-4 and active ester (rac)-2, the
temperature was required to be at or below –78 °C. This
reaction was also found to be particularly sensitive to the
temperature at which the active ester (rac)-2 was added.
Addition of the active ester (rac)-2 at room temperature
[to a stirred solution of lithiated oxazolidin-2-thione (S)-
4] lowered the diastereoselectivity to 74% de (after 5 min,
10% yield) but gradually increased to 86% de after cool-
ing in the reaction vessel for 20 minutes at –78 °C (19%
yield).
Table 2 Variation of Temperature and Diastereoselectivity
Temp (°C)
Product 5
Yield (%)
de (%)
–88
–78
–55
–10
0
(R,S)-syn-5
(R,S)-syn-5
(R,S)-syn-5
(S,S)-anti-5
(S,S)-anti-5
(S,S)-anti-5
5
30
34
60
60
57
64
88
36
8
O
Ph
OC6F5
S
S
S
C6F5O OLi
Ph
C6F5O OLi
Ph
Me
(rac)-2
N
O
N
O
LiN
Ph
O
8
Me
Me
step A
Ph
6a
Ph
6b
20
6
(S)-4-Li
With this information at hand, we next investigated the
reaction time for optimum formation of this product,
(R,S)-syn-5 at –78 °C. We chose to study this reaction
from 1 minute [after the active ester (rac)-2 was added]
through to 12 hours. Somewhat surprisingly, we found
that at the start of this reaction the levels of diastereoselec-
tivity appeared to be independent of conversion up to
~30% (Table 3). Even after 12 hours, the reaction had
only proceeded to 37% conversion giving the product, ox-
azolidin-2-thione (R,S)-syn-5, in 37% yield with 80% de
(Table 3).
step B
slow
O
fast
S
S
O
Ph
Ph
N
O
N
O
Me
Me
Ph
Ph
(R,S)-syn-5
(S,S)-anti-5
Scheme 3 Proposed mechanism for the formation of oxazolidin-2-
thione (R,S)-syn-5 derived from (S)-4-Li
This outcome is possible if the reaction proceeded via a
two-step process where the initial addition (step A) to give
intermediates 6a,b was reversible, and the elimination of
lithium pentafluorophenolate (step B) to form the oxazo-
lidin-2-thione (R,S)-syn-5 was the product-determining
step (Scheme 3). The relative diastereoselectivity of this
process appears to be a measure of the relative rates of
these addition–elimination pathways.
We next investigated a series of structurally related
pentafluorophenyl 2-arylpropionates (rac)-11, (rac)-13,
(rac)-15, and (rac)-17 (Table 5). These active esters
(rac)-11, (rac)-13, and (rac)-17 behaved similarly to the
parent active ester pentafluorophenyl 2-phenylpropionate
[(rac)-2] giving the oxazolidin-2-thiones (R,S)-12 (in
Synlett 2009, No. 6, 960–964 © Thieme Stuttgart · New York

962
N. Al Shaye et al.
LETTER
Table 4 Resolution of Pentafluorophenyl Esters (rac)-2, (rac)-7, and (rac)-9 Using Oxazolidin-2-thione (S)-4
S
S
1. n-BuLi (1.1 equiv)
THF, –78 °C
O
Ar
HN
Ph
O
N
O
O
2.
R
Ar
OC6F5
Ph
R
(S)-4
(1 equiv)
(rac)-2,7,9
(1 equiv)
(R,S)-syn-5,8,10
Entry
1
Active ester
Product
de (%)
Yield (%)
30
Recovered active ester
S
O
Ph
CO2C6F5
Ph
N
O
94
96
(S)-2, 47%, 42% ee
Me
Me
Ph
(rac)-2
(R,S)-syn-5
S
O
Ph
CO2C6F5
Ph
N
O
2
31
(S)-7, 40%, 54% ee
Et
Et
Ph
(rac)-7
(R,S)-syn-8
S
O
a
3
4
5
Ph
CO2C6F5
–
–
28
–
Ph
b
N
O
–
51c
(S)-9, 0%
i-Pr
i-Pr
Ph
(rac)-9
(R,S)-syn-10
a Reaction conditions: –78 °C, 2 h.
b Reaction conditions: –78 °C, 12 h.
c Reaction conditions: –78 °C, r.t., 12 h.
26% yield with 88% de), (R,S)-14 (in 30% yield with 92% of diastereomeric excess.16 The levels of diastereoselecti-
de), and (R,S)-18 (in 30% yield with 86% de), respective- vity were found to be independent of conversion (from 5–
ly, in similar yields (26–30%) and diastereocontrol (86– 30%) and suggests the diastereoselective addition of the
92% de, Table 5, entries 1, 2, and 4). The remaining pen- lithiated 4-phenyloxazolidin-2-thione [(S)-4-Li] to the ac-
tafluorophenyl 2-(4-chlorophenyl)propionate [(rac)-15] tive ester (rac)-2 was reversible, thus allowing the less
gave the corresponding oxazolidin-2-thione (R,S)-syn-16 reactive enantiomer of the active ester (S)-2 to be re-
in 28% yield with significantly lower levels of diastereo- turned. Competitive elimination of the resulting tetrahe-
control (64% de, Table 5, entry 3).14
dral intermediates 6a,b leads to the products (R,S)-syn-5
and (S,S)-anti-5 in a diastereomeric ratio of 94:6 (88%
de). We are currently investigating the scope and limita-
tion of this resolution process, and the results will be re-
ported in due course.
Access to enantiomerically enriched 2-phenylpropionic
acid [(R)-19, with 93% ee]15 was achieved in 70% yield by
lithium hydroxide–hydrogen peroxide mediated hydroly-
sis of oxazolidin-2-thione (R,S)-syn-5 (Scheme 4). The
oxazolidin-2-thione (S)-1 was recovered in 80% yield
with 80% sulfur retention (Scheme 4).
Acknowledgment
In conclusion, we have shown that a series of structurally
related pentafluorophenyl 2-aryl and phenyl propionates,
such as (rac)-2, can be efficiently resolved using 4-phenyl-
oxazolidin-2-thione [(S)-4] in good yield with high levels
We are grateful to the EPSRC (to E.C.) for a studentship, the Saudi
Government for financial support (to N.A.S.), and the EPSRC
National Mass Spectrometry Service (Swansea) for accurate mass
determinations.
References and Notes
S/O
S
O
O
LiOH⋅H2O
(1) Nerurkar, S. G.; Dighe, S. V.; Williams, R. L. J. Clin.
Pharmacol. 1992, 32, 935.
HN
Ph
O
N
O
OH
THF–H2O (3:1)
Me
Me
(2) (a) Sonawane, H. R.; Bellur, N. S.; Ahuja, J. R.; Kulkarni,
D. G. Tetrahedron: Asymmetry 1992, 3, 163. (b) Fuji, K.;
Node, M.; Tanaka, F.; Hosoi, S. Tetrahedron Lett. 1989, 30,
2825. (c) Corriu, J. P.; Masse, J. P. J. Chem. Soc., Chem.
Commun. 1972, 144. (d) Tamao, K.; Sumitani, K.; Kumada,
M. J. Am. Chem. Soc. 1972, 94, 4374. (e) Hayashi, T.;
Ph
(R,S)-syn-5; 93% de
(R)-19; 70%; 93% ee
(S)-1; 80%
ratio S/O = 80:20
Scheme 4 Hydrolysis of oxazolidin-2-thione (R,S)-syn-5
Synlett 2009, No. 6, 960–964 © Thieme Stuttgart · New York

LETTER
Resolution of Pentafluorophenyl Active Esters
963
Table 5 Resolution of Pentafluorophenyl Esters (rac)-11, (rac)-13, (rac)-15, and (rac)-17 Using Oxazolidin-2-thione (S)-4
S
S
O
1. n-BuLi (1.1 equiv)
THF, –78 °C
Ar
HN
Ph
O
N
O
2.
O
R
Ar
Ph
OC6F5
R
(S)-4
(1 equiv)
(rac)-11,13,15,17
(R,S)-syn-12,14,16,18
(1 equiv)
Entry
1
Active ester
Product
de (%)
Yield (%)
26
Recovered active ester
Me
Me
S
O
CO2C6F5
N
O
88
92
(S)-11, 45%, 42% ee
Me
Me
Ph
(rac)-11
(R,S)-syn-12
i-Bu
i-Bu
S
O
CO2C6F5
2
3
30
28
(S)-13, 47%, 54% ee
(S)-15, 36%, 48% ee
N
O
Me
Me
Ph
(rac)-13
(R,S)-syn-14
Cl
S
Cl
O
CO2C6F5
N
O
64
Me
Me
Ph
(rac)-15
(R,S)-syn-16
MeO
MeO
S
O
CO2C6F5
N
O
4
86
30
(S)-17, 50%, 44% ee
Me
Me
Ph
(rac)-17
(R,S)-syn-18
Konishi, M.; Fukushima, M.; Kanehira, K.; Hioki, T.;
Kumada, M. J. Org. Chem. 1983, 48, 2195. (f) Larsen,
R. D.; Corley, E. G.; Davis, P.; Reider, P. J.; Grabowski,
E. J. J. J. Am. Chem. Soc. 1989, 111, 7650. (g) Alper, H.;
Hamel, N. J. Am. Chem. Soc. 1990, 112, 2803. (h) Ohta, T.;
Takaya, H.; Kitamura, M.; Nagai, K.; Noyori, R. J. Org.
Chem. 1987, 52, 3174.
(9) For oxazolidin-2-thione (S,S)-anti-5, the PhCHN double
doublet appeared at d = 5.51 ppm (1 H, dd, J = 8.3, 3.0 Hz).
Whereas, for oxazolidin-2-thiones (R,S)-syn-5, the PhCHN
double doublet appeared at d = 5.62 ppm (1 H, dd, J = 9.2,
6.1 Hz).
(10) Eames, J.; Chavda, S.; Coumbarides, G. S.; Dingjan, M.;
Flinn, A.; Northen, J. Chirality 2007, 19, 313.
(3) For reviews, see: (a) Eames, J. Angew. Chem. Int Ed. 2000,
39, 885. (b) Eames, J. In Organic Synthesis Highlights, Vol.
5; Wiley-VCH: Weinheim, 2003, Chap. 17, 151. (c) Dehli,
J. R.; Gotor, V. Chem. Soc. Rev. 2002, 31, 365. (d) Dehli,
J. R.; Gotor, V. ARKIVOC 2002, (v), 196.
(4) (a) Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.;
Motevalli, M.; Northen, J.; Yohannes, Y. Synlett 2006, 101.
(b) Boyd, E.; Chavda, S.; Eames, J.; Yohannes, Y.
Tetrahedron: Asymmetry 2007, 18, 476.
(11) Boyd, E.; Chavda, S.; Coulbeck, E.; Coumbarides, G. S.;
Dingjan, M.; Eames, J.; Flinn, A.; Motevalli, M.; Northen,
J.; Yohannes, Y. Tetrahedron: Asymmetry 2007, 18, 2515.
(12) The ee was determined through hydrolysis of the active ester
and derivatization of the parent 2-phenylpropionic acid. For
further information, see ref. 15.
(13) For the mutual kinetic resolution of active ester (rac)-2 with
4-phenyloxazolidin-2-thione (rac)-4, gave the
corresponding (RS,SR)-(rac)-syn-5 in 55% yield with 96%
(5) (a) Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.;
Northen, J.; Yohannes, Y. Tetrahedron Lett. 2005, 46,
2897. (b) Yohannes, Y. PhD Thesis; University of London:
UK, 2004.
(6) Chavda, S.; Coulbeck, E.; Dingjan, M.; Eames, J.; Flinn, A.;
Northen, J. Tetrahedron: Asymmetry 2008, 19, 1536.
(7) (a) Delaunay, D.; Toupet, L.; Corre, M. L. J. Org. Chem.
1995, 60, 6604. (b) Wu, Y.; Yang, Y.-Q.; Hu, Q. J. Org.
Chem. 2004, 69, 3990.
de. For further information, see ref. 6.
(14) This lower diastereocontrol was not due to in situ
racemization of active ester (rac)-15 nor epimerization of
the resulting oxazolidin-2-thione (R,S)-syn-16 as this adduct
can be made stereospecifically by addition of (R)-15 to the
lithiated 4-phenyloxazolidin-2-thione (S)-4-Li.
(15) The ee was determined by derivatisation with (R)-1-
phenylethanol using a DMAP-mediated DCC coupling
procedure.
(8) The relative configuration of this adduct was determined
(16) Representative Experimental Procedure:(2R,4S)-3-(2-
Phenylpropionyl)-4-phenyloxazolidin-2-thione [(R,S)-
syn-5]
through stereospecific synthesis.
Synlett 2009, No. 6, 960–964 © Thieme Stuttgart · New York

964
N. Al Shaye et al.
LETTER
n-Butyllithium (0.36 mL, 2.5 M in hexane, 0.90 mmol) was
added to a stirred solution of 4-phenyloxazolidin-2-thione
(S)-4 (0.15 g, 0.84 mmol) in THF (5 mL) at –78 °C. After
stirring for 1 h, a solution of pentafluorophenyl 2-phenyl-
propionate [(rac)-2, 0.26 g, 0.84 mmol] in THF (1 mL) was
added. The resulting mixture was stirred for 2 h at –78 °C.
The reaction was quenched with H2O (10 mL). The organic
layer was extracted with CH2Cl2 (2 × 10 mL), dried
(MgSO4), and evaporated under reduced pressure to give a
mixture of diastereomeric oxazolidin-2-thiones syn-5 and
anti-5 (ratio 94:6 syn/anti). The crude residue was purified
by flash chromatography on SiO2 eluting with light PE (bp
40–60 °C)–Et2O (7:3) to give the oxazolidin-2-thione (R,S)-
syn-5 (77 mg, 30%) as a white solid and the pentafluoro-
phenyl 2-phenylpropionate (S)-2 (0.123 g, 47%) as a
colorless liquid.
Oxazolidin-2-thione (R,S)-syn-5: Rf = 0.67 [light PE (bp
40–60 °C)–Et2O, 1:1]; mp 87–89 °C [lit.6 (S,R) 84–86 °C];
[a]D20 +66.1 (c 3.6, CHCl3) [lit. (S,R) [a]D20 –58.3 (c 4.0,
CHCl3)]. IR (CHCl3): nmax = 1708 (C=O), 1216 (C=S) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.20–7.08 (6 H, m, 6 × CH,
PhA and PhB), 6.94 (2 H, dt, J = 6.9, 1.8 Hz, 2 × CH, PhA),
6.88 (2 H, dt, J = 7.0, 1.8 Hz, 2 × CH, PhB), 5.98 (1 H, q, J =
6.9 Hz, PhCHCH3), 5.62 (1 H, dd, J = 9.2, 6.1 Hz, PhCHN),
4.68 (1 H, t, J = 9.2 Hz, CHAHBO), 4.20 (1 H, dd, J = 9.2, 6.1
Hz, CHAHBO), 1.35 (3 H, d, J = 6.9 Hz, PhCHCH3).
13C NMR (100 MHz, CDCl3): 185.2 (C=S), 174.8 (C=O),
139.1 and 136.9 (2 × i-C; 2 × Ph), 128.8,2 128.7,1 128.5,2
128.3,2 127.11 and 126.42 (10 × CH, 2 × Ph), 73.6 (CH2O),
62.6 (PhCHN), 43.9 (PhCHCH3), 18.7 (PhCHCH3). HRMS:
m/z calcd for C18H18NO2S [MH+]: 312.1053; found:
312.1054.
Pentafluorophenyl 2-phenylpropionate (S)-2: Rf = 0.63 [light
PE (40–60 °C)–Et2O, 9:1]; [a]D20 +40.8 (c 4.6, CHCl3) {ca.
55% ee based on lit.10 (S) [a]D20 +74.5 (c 4.9, CHCl3); lit.11
(R) [a]D20 –75.0 (c 3.3, CHCl3)}. IR (film): nmax = 1784
(C=O) cm–1. 1H NMR (400 MHz, CDCl3): d = 7.41–7.28 (5
H, m, 5 × CH, Ph), 4.07 (1 H, q, J = 7.2 Hz, CH3CH), 1.64
(3 H, d, J = 7.2 Hz, CH3CH). 13C NMR (100 MHz, CDCl3):
d = 170.6 (OC=O), 141.1 [142.40 and 139.90, 2 C, ddt,
1JC,F = 251.3 Hz, 2JC,F = 12.2 Hz, 3JC,F = 3.8 Hz, C(2)-F],
139.4 [140.70 and 138.18, 1 C, dtt, 1JC,F = 253.2 Hz,
2JC,F = 13.4 Hz, 3JC,F = 4.2 Hz, C(4)-F], 138.7 (i-C, Ph),
137.8 [139.05 and 136.58, 2 C, dtdd, 1JC,F = 249.1 Hz,
2JC,F = 14.5 Hz, 3JC,F = 5.7 Hz, 4JC,F = 3.1 Hz, C(3)-F],
128.9, 127.8, 127.5 (3 × CH, Ar), 125.2 (1 C, tdt, 2JC,F = 14.2
Hz, 4JC,F = 4.2 Hz, 3JC,F = 2.0 Hz, i-CO, OC6F5), 45.1
(PhCH), 18.5 (CH3CH). 19F NMR (378 MHz, CDCl3):
d = –152.6 (2 F, d, 3JF,F = 20.9 Hz, Fortho), –157.9 (1 F, t,
3JF,F = 20.9 Hz, Fpara), –162.3 (2 F, t, 3JF,F = 20.9 Hz, Fmeta).
HRMS: m/z calcd for C15H9F5O2 [M+]: 316.0517; found:
316.0514.
Synlett 2009, No. 6, 960–964 © Thieme Stuttgart · New York