A new strategy for the synthesis of optically active benzylic fluorides and corresponding five-membered heteroaromatic analogues

Article abstract of DOI:10.1016/j.tetlet.2007.06.007

Benzylic fluorides, as well as five-membered heterocycles, have been obtained in high ee's through cycloaddition reactions starting from easily accessible optically active propargylic fluorides.

Full text of DOI:10.1016/j.tetlet.2007.06.007

Tetrahedron Letters 48 (2007) 5435–5438
A new strategy for the synthesis of optically active benzylic
fluorides and corresponding five-membered
heteroaromatic analogues
*
´
´
´
Danielle Gree and Rene Gree
`
`
Universite´ de Rennes 1, Laboratoire de Synthese et Electrosynthese Organiques, CNRS UMR 6510,
Avenue du Ge´ne´ral Leclerc, 35042 Rennes Cedex, France
Received 28 March 2007; accepted 4 June 2007
Available online 9 June 2007
Abstract—Benzylic fluorides, as well as five-membered heterocycles, have been obtained in high ee’s through cycloaddition reactions
starting from easily accessible optically active propargylic fluorides.
Ó 2007 Elsevier Ltd. All rights reserved.
The presence of fluorine atom(s) in organic molecules
strongly modifies their physical, chemical and biological
properties.1 The selective replacement of C–H or C–OH
bonds by C–F bonds has been already of much use in
bioorganic and medicinal chemistry.2 However, the ste-
reoselective introduction of fluorine is often a key step in
the preparation of target molecules, especially if opti-
cally active fluorides are required. Many bioactive mol-
ecules and/or drugs have an H or an OH in benzylic
position. Therefore, their fluorinated analogues appear
as potentially useful target molecules, especially in
medicinal chemistry. However, due to synthetic prob-
lems, only a limited number of representative com-
pounds have been prepared to date.3 Their synthesis is
even more challenging if optically active benzylic fluo-
rides are considered. Only a few synthetic methods have
been developed until now, and most of them use a C–F
disconnection strategy starting from benzylic precur-
sors.4 Nucleophilic and dehydroxy-fluorination methods
have been studied but they have strong limitations either
in scope or in stereoselectivity, or both (Scheme 1). For
instance, it has been clearly established that the substitu-
tion by Fꢀ is highly stereocontrolled only if there is a
strong electron-withdrawing group (R3) in the para po-
sition to the benzylic fluoride chain. For other substitu-
ents, the stabilisation of the intermediate carbenium ions
induced partial or complete racemisations.5,6 On the
other hand, for electrophilic fluorinations excellent
F
OLG
R1
C-F
disconnection
R1
R3
R3
-
R2
F
R2
Diels-Alder +
aromatisation
C-C
disconnections
F
R1
F
c
R2
b
1,3 dipolar
R2
R1
a
cycloadditions
Scheme 1. Strategy towards the synthesis of optically active benzylic
fluorides and five-membered heterocycles.
results have been obtained, both under stoichiometric
and catalytic reaction conditions, but they require in
every case an electron-withdrawing group (R1) to allow
for the use of electrophilic fluorinating reaction
conditions.7
As part of our programme in asymmetric monofluorina-
tion and applications to the synthesis of bioactive mole-
cules analogue,8 we designed a novel strategy towards
such optically active benzylic fluorides, by using com-
pletely different disconnections: the basic idea was to
start from easily accessible optically active propargylic
fluorides8,9 and to create the C–C bonds during the syn-
thesis by Diels–Alder followed by aromatisation reac-
tions (Scheme 1).
*
Corresponding author. Tel.: +33 02 23 23 65 39; fax: +33 02 23 23 69
78; e-mail: danielle.gree@univ-rennes1.fr
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.007

5436
D. Gre´e, R. Gre´e / Tetrahedron Letters 48 (2007) 5435–5438
Another key advantage of this new approach is that it
could be an easy entry towards heteroaromatic deriva-
tives by using various cycloadditions such as the 1,3
dipolar cycloadditions. Furthermore, these primary ad-
ducts appear as versatile intermediates towards the
preparation of chemical libraries. The purpose of this
communication is to demonstrate, on selected examples,
that such strategy has allowed the preparation of these
target molecules with high ee’s.
oxy-fluorination was completely stereoselective, afford-
ing 3c in 96% de. The same yields and selectivities
were obtained in reactions performed at ꢀ10 °C or at
ꢀ50 °C.11 These results are in agreement with previous
studies on the dehydroxy-fluorination of propargylic
alcohols with electron-withdrawing groups in the termi-
nal position.12
In the next step, the Diels–Alder reaction was performed
on (+)-3a with excess dimethylbutadiene under reflux,
affording cyclohexadiene 5a, characterized only by
NMR and directly submitted to aromatisation by using
DDQ in toluene. The benzylic fluoride (ꢀ)-6a was ob-
tained in 65% overall yield from (+)-3a (Scheme 3). Its
optical purity (96% ee) was easily established by 1H
and 19F NMR in the presence of Eu(hfc)3 and by com-
parison with the data obtained from a racemic sample
prepared from ( )-3a by the same route. The same series
of reactions were performed starting from (+)-3a and
using 2,3-dimethoxybutadiene, affording (ꢀ)-8a in 51%
overall yield. In the same way, (+)-6b was obtained
in 46% overall yield from the reaction of (+)-3b
with dimethylbutadiene followed by aromatisation.
We also established by using the same NMR experi-
ments as for (ꢀ)-6a, that these two benzylic fluorides,
as well as intermediate 7a, have 96% ee’s. These
results demonstrated unambiguously that no racemisa-
tion had occurred at any stage of this synthetic
scheme.13
Two propargylic fluorides, (+)-3a and (+)-3b, have been
selected as test molecules. They have been prepared by a
diethylaminosulfurtrifluoride (DAST) mediated dehydr-
oxy-fluorination route from the corresponding propar-
gylic alcohols, as indicated in Scheme 2.
Ketone (ꢀ)-2a was prepared from (S)-butynol following
literature procedures.10 A similar two-step sequence was
followed for the preparation of the ester (ꢀ)-2b in 70%
overall yield from 1. For both propargylic alcohols,
NMR in the presence of Eu(hfc)3 established a 96%
ee. After optimisation of the reaction conditions, the
dehydroxy-fluorination with DAST were performed at
ꢀ13 °C in the case of (ꢀ)-2a and ꢀ30 °C for (ꢀ)-2b,
affording the corresponding propargylic fluorides in
70% and 65% yields, respectively. On these fluorides,
the ee’s could not be established clearly, neither by
NMR nor by chromatography on chiral columns. How-
ever since their cycloadducts demonstrated also ee’s of
96%, as shown later, it was concluded that no racemisa-
tion has occurred during these fluorinations. As a com-
plementary test the mandelate ester 2c was also prepared
in 28% overall yield and 96% de from (ꢀ)-4. Under the
same conditions as for (ꢀ)-2b (at ꢀ30 °C), the dehydr-
Then, extension to five-membered heteroaromatic sys-
tems was studied. The reaction of benzyl azide with
(+)-3a afforded in 75% overall yield a 2:1 mixture of
triazoles (ꢀ)-9a and (ꢀ)-10a, while the reaction of (+)-
3b yielded in 80% overall yield a 55:45 mixture of (+)-
9b and (ꢀ)-10b (Scheme 4). All these triazoles have been
isolated by chromatography on SiO2 and by using the
same NMR experiments as previously described, they
have demonstrated 96% ee’s. Similar cycloaddition reac-
tions were performed using nitrile oxides as 1,3 dipoles.
They were prepared from nitroethane by Mukaiyama’s
procedure.14 Addition on (+)-3a afforded in 83% overall
yield a 91:9 mixture of regioisomers (+)-11a and (ꢀ)-
12a, separated by chromatography on SiO2. Starting
from (+)-3b, the same reaction afforded in 71% overall
yield a 92:8 mixture of (+)-11b and 12b. The major isox-
azole (+)-11b was isolated by chromatography on SiO2.
Here also, the ee’s were established as 96% by NMR on
the three pure previous isoxazoles, as well as on mixtures
of (ꢀ)-11b and 12b for the latter derivative.15
O
O
F
OH
Me
DAST (1.1 eq)
CH2Cl2, -13°C
70%
Ph
Ph
Me
(+)-3a
(-)-2a
1) nBuLi, -78°C
then PhCHO
2) MnO2
3) PPTS, EtOH, 50°
60% overall yield
OTHP
DHP, APTS
86%
(S)-Butynol
H
Me
1
2) PPTS, EtOH,
1) nBuli, -78°C
then ClCO2Et
50°C, 70% overall yield
O
O
F
OH
Me
OTBS
Me
1) LiOH, THF, 89%
DAST (1.1 eq)
CH2Cl2, -30°C
65%
EtO
EtO
Me
(+)-3b
(-)-2b
(-)-4
O
2 steps
90%
(S)-Butynol
F
Z
R
R
F
EtO
R
R
R
R
DDQ
Me
Me
3) CH3CO2H,
(+)-3
2) (S)-Methyl Mandelate
THF-H2O, 65°C, 58%
Toluene
80°C
DCC, DMAP, 55%
OH
Z
DAST (1.1 eq)
CH2Cl2
O
O
O
F
5a
7a
5b
R = Me; Z = COPh
(-)-6a
(-)-8a
(+)-6b
Ph
MeO2C
Ph
R = OMe; Z = COPh
R = Me; Z = CO2Et
-10°C to -50°C
65%
Me
O
Me
MeO2C
3c
2c
Scheme 3. Diels–Alder reactions on optically active propargylic
Scheme 2. Synthesis of the optically active propargylic fluorides.
fluorides, followed by aromatisation.

D. Gre´e, R. Gre´e / Tetrahedron Letters 48 (2007) 5435–5438
5437
´
´
8. Prakesch, M.; Gree, D.; Gree, R. Acc. Chem. Res. 2002,
F
F
´
´
35, 175; Filmon, J.; Gree, D.; Gree, R. J. Fluorine Chem.
2001, 107, 271; Kerouredan, E.; Prakesch, M.; Gree, D.;
Gree, R. Lett. Org. Chem. 2004, 1, 87; Manthati, V.; Gree,
D.; Gree, R. Eur. J. Org. Chem. 2005, 3825; Manthati, V.
L.; Murthy, A. S. K.; Caijo, F.; Drouin, D.; Lesot, P.;
Gree, D.; Gree, R. Tetrahedron: Asymmetry 2006, 17,
2306, and references cited therein.
Me
Me
´
BnN
N
N
BnN3
´
´
+
N
Z
´
Z
N
N
(45°C, 3a)
(60°C, 3b)
Bn
(-)-9a
Z = COPh
Z = CO2Et
(-)-10a
´
´
(+)-9b
(-)-10b
(+)-3
F
F
9. For another recent synthesis of propargylic fluorides see:
Carroll, L.; Pacheco, Ma. C.; Garcia, L.; Gouverneur, V.
Chem. Commun. 2006, 4113.
Me
N
Me
Me
EtNO2
O
+
10. Obrecht, D. Helv. Chim. Acta 1989, 72, 447.
N
PhNCO,
Z
Z
O
11. Main spectroscopical data for propargylic fluorides.
Compound (+)-3a: 1H NMR (300 MHz, CDCl3) 8.20–
8.13 (m, 2H); 7.69–7.49 (m, 3H); 5.50 (dq, 1H, JHF = 47.8,
J = 6.6); 1.76 (dd, 3H, JHF = 22.6, J = 6.6). 13C NMR
(75 MHz, CDCl3) 177.1 (d, J = 2.6); 136.1, 134.6, 129.6,
128.7, 89.9 (d, J = 26.0); 84.2 (d, J = 9.7); 78.5 (d,
J = 168.8); 21.7 (d, J = 24.2). 19F NMR (282 MHz,
Et3N, 50°C
Toluene
Me
(+)-11a
Z = COPh
Z = CO2Et
(-)-12a
(+)-11b
12b
Scheme 4. Azide and nitrile oxide cycloadditions on optically active
propargylic fluorides.
21
CDCl3) ꢀ170.35 (dq, J = 47.8, J = 22.6). ½aꢁD +4.2 (c
0.54, CHCl3). Compound (+)-3b: 1H NMR (300 MHz,
CDCl3) 5.33 (dq, 1H, JHF = 47.7, J = 6.7); 4.27 (q, 2H,
J = 7.2); 1.66 (dd, 3H, JHF = 22.7, J = 6.7); 1.33 (t, 3H,
J = 7.2). 13C NMR (75 MHz, CDCl3) 152.8 (d, J = 3.0);
83.2 (d, J = 26.2); 78.6 (d, J = 9.7); 78.2 (d, J = 169.3);
62.4; 21.5 (d, J = 24.2); 13.9. 19F NMR (282 MHz,
In conclusion, these preliminary results clearly estab-
lished that benzylic fluorides, as well as the correspond-
ing five-membered heterocycles, are accessible in high
ee’s by using this new route since very little, if any, rac-
emisation occurred under such reaction conditions. This
strategy will be used for the preparation of fluorinated
analogues of bioactive molecules. Furthermore, the
extension to other propargylic fluorides and to other
cycloadditions and cyclo-condensations are under active
study in our group.
21
CDCl3) ꢀ172.02 (dq, J = 47.9, J = 22.7). ½aꢁD +17.9 (c
1
0.54, CHCl3). Compound 3c: H NMR (300 MHz, C6D6)
7.39–7.02 (m, 5H); 6.02 (s, 1H); 4.56 (dq, 1H, JHF = 47.7,
J = 6.7); 3.17 (s, 3H); 0.95 (dd, 3H, JHF = 22.5, J = 6.7).
13C NMR (75 MHz, C6D6) 168.0; 152.0 (d, J = 2.9); 133.1;
129.4; 128.8; 128.1; 85.1 (d, J = 26.4); 78.5 (d, J = 9.7);
78.1 (d, J = 170.1); 52.1; 20.7 (d, J = 24.0). 19F NMR
(282 MHz, CDCl3) ꢀ172.18 (the signal for the other
diastereoisomer is at ꢀ172.16).
References and notes
´
´
12. Gree, D.; Madiot, V.; Gree, R. Tetrahedron Lett. 1999, 40,
´
´
6399; Madiot, V.; Lesot, P.; Gree, D.; Courtieu, J.; Gree,
R. Chem. Commun. 2000, 169.
1. Kitazume, T.; Yamazaki, T. Experimental Methods in
Organic Fluorine Chemistry; Gordon and Breach Science
Publishers: Tokyo, 1998; Hudlicky, M.; Pavlath, A. E.
Chemistry of Organic Fluorine Compounds II: A Critical
Review; ACS Monograph 187; ACS: Washington, DC,
1995; Organofluorine Chemistry: Principles and Commer-
cial Applications; Banks, R. E., Smart, B. E., Tatlow, J. C.,
Eds.; Plenum: New York, 1994, and references cited
therein.
2. Ojima, I.; McCarthy, J. R.; Welch, J. T. Biomedical
Frontiers in Fluorine Chemistry, ACS Symposium Series
639. ACS: Washington, DC, 1996; Welch, J. T.; Eswara-
krishnan, S. Fluorine in Bioorganic Chemistry; Wiley
Interscience: New York, 1991; Welch, J. T. Tetrahedron
1987, 43, 3123, and references cited therein.
13. Main spectroscopical data for benzylic fluorides: Com-
pound (ꢀ)-6a: 1H NMR (300 MHz, CDCl3) 8.00–7.45 (m,
5H); 7.48 (s, 1H); 7.16 (s, 1H); 5.90 (dq, 1H, JHF = 47.6;
J = 6.3); 2.39 (s, 3H); 2.29 (s, 3H); 1.69 (dd, 3H,
JHF = 24.0, J = 6.3). 13C NMR (75 MHz, CDCl3) 197.6;
140.4; 139.8 (d, J = 19.3); 138.0; 135.6 (d, J = 1.7); 133.5
(d, J = 4.8); 133.0; 130.5; 130.2; 128.4; 127.0 (d, J = 9.0);
88.5 (d, J = 165.4); 23.8 (d, J = 25.6); 20.0; 19.4. 19F
NMR (282 MHz, CDCl3) ꢀ167.26 (dq, J = 47.8,
21
J = 23.9). ½aꢁD ꢀ87.8 (c 0.64, CHCl3). Compound (ꢀ)-
1
8a: H NMR (300 MHz, CDCl3) 7.82–7.40 (m, 5H); 7.22
(s, 1H); 6.90 (s, 1H); 5.95 (dq, 1H; JHF = 47.5, J = 6.2);
4.02 (s, 3H); 3.81 (s, 3H); 1.69 (dd, 3H, JHF = 24.0,
J = 6.2). 13C NMR (75 MHz, CDCl3) 196.5; 151.6; 147.3
(d, J = 1.7); 138.1; 136.8 (d, J = 19.5); 133.0; 130.2; 128.5;
127.9 (d, J = 4.8); 112.7; 108.4 (d, J = 10.3); 88.5 (d,
J = 165.7); 56.1 (2C); 24.0 (d, J = 25.8). 19F NMR
(282 MHz, CDCl3) ꢀ166.46 (dq, J = 47.5, J = 24.0).
´
3. Sai Krishna Murthy, A.; Tardivel, R.; Gree, R. Product
Subclass 6: Benzylic Fluorides, Science of Synthesis. Georg
Thieme Verlag, 2006; p 295.
´
´
4. Prakesch, M.; Gree, D.; Gree, R. Asymmetric Synthesis of
Monofluorinated Compounds having the Fluorine Atom
Vicinal to p-Systems. In Fluorine Containing Synthons;
Soloshonok, V. A., Ed.; ACS Publications Division and
Oxford University Press: Washington, DC, 2005; p 173.
5. Fritz-Langhals, E. Tetrahedron Lett. 1994, 35, 1581; Fritz-
Langhals, E. Tetrahedron: Asymmetry 1994, 5, 981.
21
½aꢁD ꢀ60.8 (c 0.74, CHCl3). Compound (+)-6b: 1H
NMR (300 MHz, CDCl3): 7.75 (s, 1H); 7.46 (s, 1H);
6.43 (dq, 1H, JHF = 48.6, J = 6.2); 4.36 (q, 2H, J = 7.1);
2.35 (s, 3H); 2.31 (s, 3H); 1.65 (dd, 3H, JHF = 24.3,
J = 6.2); 1.41 (t, 3H, J = 7.1). 13C NMR (75 MHz,
CDCl3) 166.7 (d, J = 0.7); 142.1 (d, J = 19.2); 142.0 (d,
J = 1.0); 135.8 (d, J = 1.4); 131.4; 126.5 (d, J = 13.0);
124.4 (d, J = 4.5); 88.7 (d, J = 165.1); 60.8; 23.7 (d,
J = 25.4); 20.0; 19.3; 14.3. 19F NMR (282 MHz, CDCl3)
6. Paulsen, H.; Antons, S.; Brandes, A.; Lo¨gers, M.; Muller,
¨
S. N.; Naab, P.; Schmeck, C.; Schneider, S.; Stoltefuss, J.
Angew. Chem., Int. Ed. 1999, 38, 3373.
7. For recent reviews on asymmetric fluorinations, including
electrophilic fluorinations, see: Ma, J.-A.; Cahard, D.
Chem. Rev. 2004, 104, 6119; Hamashima, Y.; Sodeoka, M.
Synlett 2006, 1467; Bobbio, C.; Gouverneur, V. Org.
Biomol. Chem. 2006, 4, 2065, and references cited therein.
21
ꢀ170.95 (dq, J = 48.6, J = 24.3). ½aꢁD +22.4 (c 0.32,
CHCl3).
14. Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82,
5339.

5438
D. Gre´e, R. Gre´e / Tetrahedron Letters 48 (2007) 5435–5438
21
15. Main spectroscopical data for 1,3 dipolar cycloadducts:
Compound (ꢀ)-9a: 1H NMR (300 MHz, CDCl3) 8.41–8.35
(m, 2H); 7.65–7.30 (m, 8H); 6.51 (dq, 1H, JHF = 46.6,
J = 6.7); 5.91 (d, 1H, J = 14.9); 5.86 (d, 1H, J = 14.9); 1.49
(dd, 3H, JHF = 23.6, J = 6.7). 13C NMR (75 MHz, CDCl3)
186.9; 143.0 (d, J = 2.3); 141.3 (d, J = 19.2); 136.7; 134.9;
133.3; 130.7; 128.9; 128.6; 128.3; 128.0; 84.6 (d, J = 169.6);
53.9 (d, J = 7.9); 20.5 (d, J = 23.7). 19F NMR (282 MHz,
J = 23.6). ½aꢁD ꢀ5.9 (c 0.98, CHCl3). Compound (+)-11a:
1H NMR (300 MHz, CDCl3) 7.82–7.50 (m, 5H); 5.58 (dq,
1H, JHF = 46.3, J = 6.6); 2.30 (s, 3H); 1.71 (dd, 3H,
JHF = 23.6, J = 6.6). 13C NMR (75 MHz, CDCl3) 189.2 (d,
J = 0.9); 169.8 (d, J = 20.8); 159.2 (d, J = 1.8); 137.7;
134.0; 129.2; 128.9; 117.2 (d, J = 3.4); 81.4 (d, J = 171.1);
19.1 (d, J = 24.7); 11.1. 19F NMR (282 MHz, CDCl3)
21
ꢀ171.38 (dq, J = 46.3, J = 23.6). ½aꢁD +29.0 (c 0.59,
21
CDCl3) ꢀ182.14 (dq, J = 46.6, J = 23.6). ½aꢁD ꢀ49.1 (c
CHCl3). Compound (ꢀ)-12a: 1H NMR (300 MHz, CDCl3)
8.17–8.12 (m, 2H); 7.69–7.50 (m, 3H); 6.22 (dq, 1H,
JHF = 46.7; J = 6.6); 2.52 (d, 3H, JHF = 1.6); 1.73 (dd, 3H,
JHF = 23.5, J = 6.6). 13C NMR (75 MHz, CDCl3) 182.7;
161.0 (d, J = 7.1); 159.5; 135.5; 134.2; 130.2; 128.7; 125.3;
(d, J = 24.9); 83.3 (d, J = 163.5); 21.3 (d, J = 24.9); 11.4 (d,
J = 4.0). 19F NMR (282 MHz, CDCl3) ꢀ176.7 (dqq,
0.36, CHCl3). Compound (ꢀ)-10a: 1H NMR (300 MHz,
CDCl3): 7.64–7.17 (m, 10H); 5.73 (d, 1H, J = 14.6); 5.68 (d,
1H, J = 14.6); 5.43 (dq, 1H, JHF = 47.7, J = 6.5); 1.72 (dd,
3H, JHF = 23.7, J = 6.5). 13C NMR (75 MHz, CDCl3):
186.8; 136.7; 134.5; 134.4; 129.4; 128.8 (2C); 128.6; 128.2;
82.7 (d, J = 165.8); 53.4; 19.9 (d, J = 24.5). 19F NMR
21
21
(282 MHz, CDCl3) ꢀ162.83 (dq, J = 47.7, J = 23.7). ½aꢁD
J = 48.3, J = 23.5, J = 1.6). ½aꢁD ꢀ20.2 (c 0.47, CHCl3).
ꢀ20.0 (c 0.18, CHCl3). Compound (+)-9b: 1H NMR
(300 MHz, CDCl3) 7.34–7.20 (m, 5H); 6.45 (dq, 1H,
JHF = 46.2, J = 6.7); 5.82 (d, 1H, J = 15.0); 5.63 (d, 1H,
J = 15.0); 4.40 (q, 2H, J = 7.1); 1.40 (t, 3H, J = 7.1); 1.35
(dd, 3H, JHF = 23.6, J = 6.7). 13C NMR (75 MHz, CDCl3)
161.0; 140.1 (d, J = 20.2); 135.9 (d, J = 2.9); 134.9; 128.8;
128.6; 127.7; 83.9 (d, J = 170.0); 61.4; 53.9 (d, J = 7.5); 20.5
(d, J = 23.9); 14.2. 19F NMR (282 MHz, CDCl3) ꢀ183.65
Compound (+)-11b: 1H NMR (300 MHz, CDCl3) 6.23
(dq, 1H, JHF = 46.2, J = 6.6); 4.35 (q, 2H, J = 7.1); 2.48 (s,
3H); 1.75 (dd, 3H, JHF = 23.6, J = 6.6); 1.39 (t, 3H,
J = 7.1). 13C NMR (75 MHz, CDCl3) 173.0 (d, J = 19.2);
161.3 (d, J = 1.4); 159.8 (d, J = 1.4); 109.5 (d, J = 3.2); 82.0
(d, J = 171.2); 61.1; 19.0 (d, J = 24.8); 14.1; 11.6. 19F NMR
21
(282 MHz, CDCl3) ꢀ176.70 (dq, J = 47.1, J = 23.6). ½aꢁD
+32.5 (c 0.46, CHCl3). Compound 12b: 1H NMR
(300 MHz, CDCl3) 6.24 (dq, 1H, JHF = 46.6, J = 6.6);
4.44 (q, 3H, J = 7.1); 2.45 (d, 3H, JHF = 1.6); 1.64 (dd, 3H,
JHF = 23.4, J = 6.6); 1.42 (t, 3H, J = 7.1). 13C NMR
(75 MHz, CDCl3) 159.6; 157.1 (d, J = 1.2); 154.3 (d,
J = 7.7); 124.4 (d, J = 25.4); 84.4 (d, J = 163.7); 62.3;
21.3 (d, J = 25.1); 14.1; 11.4 (d, J = 3.8). 19F NMR
(282 MHz, CDCl3) ꢀ177.98 (dqq, J = 46.6, J = 23.4,
J = 1.6).
21
(dq, J = 46.2, J = 23.6). ½aꢁD +15.1 (c 0.57, CHCl3).
Compound (ꢀ)-10b: 1H NMR (300 MHz, CDCl3) 7.32–
7.30 (m, 5H); 6.11 (dq, 1H, JHF = 47.2, J = 6.6); 5.91 (s,
2H); 4.38 (q, 2H, J = 7.1); 1.86 (dd, 3H, JHF = 23.6,
J = 6.6). 13C NMR (75 MHz, CDCl3) 158.2 (d, J = 1.3);
149.4 (d, J = 21.5); 134.9; 128.8; 128.4; 127.9; 125.1 (d,
J = 3.2); 82.8 (d, J = 165.6); 62.2; 53.9; 19.6 (d, J = 24.7);
14.0. 19F NMR (282 MHz, CDCl3) ꢀ166.33 (dq, J = 47.2,