Synthetic Studies Towards the Synthesis of 6-Substituted 3-Fluoro-5,6-dihydropyran-2-ones 1

Article abstract of DOI:10.1055/s-0036-1588534

The synthesis of 6-substituted 3-fluoro-5,6-dihydropyran-2-ones under mild conditions is described. The key step of the synthesis involves a Julia-Kocienski olefination.

Full text of DOI:10.1055/s-0036-1588534

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–D
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A
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S. K. Mandal et al.
Letter
Synlett
Synthetic Studies Towards the Synthesis of 6-Substituted 3-Fluoro-
5,6-dihydropyran-2-ones1
Samir K. Mandal*a
Apurba Sarkara
Puskin Chakrabortyb
0
0
0
0
0-
0
0
3
0-
3
0
7
1-
7
8
X
F
[O]
Julia–Kocienski
O
R
O
O
R
OH
R
OH
Ashoke P. Chattopadhyayc
R = aryl (7 examples)
alkyl (1 example)
Total 8 examples
Upto 44% overall yield
a Department of Chemistry, Saldiha College, Saldiha-722173,
India
samirmandal2004@gmail.com
b Department of Organic Chemistry, Indian Association for the
Cultivation of Science, Jadavpur-700032, India
c Department of Chemistry, University of Kalyani, Kalyani-741235,
India
Received: 26.06.2017
Accepted after revision: 11.07.2017
Published online: 17.08.2017
properties of the molecule.13 Because it is similar in size to
hydrogen and has strong electron-withdrawing properties,
fluorine enhances the Michael-acceptor capabilities of con-
jugated double bonds of α-fluoro α,β-unsaturated carbonyl
compounds.9
Introduction of fluorine can be achieved either by a
building-block approach or by direct introduction.14 Regio-
and stereoselective fluorination is of topical interest in ar-
eas such as agrochemicals15 and pharmaceuticals.16 The
Witting reaction, Horner–Wordsworth–Emmons reaction,
the Julia reaction, and other reactions have been employed
for this purpose.17 The Julia–Kocienski olefination is a con-
venient method for the introduction of a fluorovinyl unit.18
In line with our previous reports on the syntheses of vari-
ous lactones,19 we describe here the first synthesis of 6-
substituted 3-fluoro-5,6-dihydropyran-2-one analogues by
using a Julia–Kocienski olefination as a key step under mild
conditions.
Several hetaryl sulfones have been used in the Julia–
Kocienski olefination reaction. In particular, benzothiazole
sulfones (BT-sulfones) have been widely used.20,21 There-
fore, BT-sulfone 321a was considered for our synthetic plan,
and our retrosynthetic approach to the synthesis of lactone
1 is outlined in Scheme 1. Lactone 1 might be synthesized
by the lactonization of 2, which in turn might be synthe-
sized by the condensation reaction of BT-sulfone 3 with a β-
hydroxy aldehyde 4. Aldehyde 4 should be readily accessible
by oxidative cleavage of a homoallylic alcohol 5.
In a preliminary study, homoallylic alcohol 5a, prepared
from benzaldehyde by a Reformatsky reaction, was treated
with RuCl3·NaIO4 at room temperature in the presence of
TBAI to yield aldehyde 4a (Scheme 2).22 Conversion of the
alkene into an aldehyde in presence of the unprotected al-
cohol group occurred within 60 minutes (checked by TLC),
and was confirmed by NMR spectroscopy of the condensa-
tion product. Because of the instability of β-hydroxy alde-
DOI: 10.1055/s-0036-1588534; Art ID: st-2017-d0518-l
Abstract The synthesis of 6-substituted 3-fluoro-5,6-dihydropyran-2-
ones under mild conditions is described. The key step of the synthesis
involves a Julia–Kocienski olefination.
Key words fluorosulfones, lactones, dihydropyranones, Julia–Kocienski
olefination
6-Substituted α,β-unsaturated δ-lactones are pharma-
cologically important molecules that are used as antimalar-
ial,2 anticancer,3 antitumor antibiotic,4 and antifungal
agents.5 The activity of this class of naturally occurring lac-
tones is due to the presence of the electrophilic α,β-unsatu-
rated lactone moiety [e.g. (+)-boronolide and (–)-goniothal-
amin (Figure 1)],6 but the ability to build in structural mod-
ifications is important.7 Moreover, these lactone natural
products can include complex polyketide8 or polyacetoxyl-
ated9 side chains in their structural features. This has en-
couraged the synthesis of analogues rather than synthesis
of the conventional, more complex, naturally occurring
molecules.10
OAc OAc
Michael acceptor
essential for activity
O
O
OAc
O
O
(+)-Boronolide
(–)-Goniothalamin
Figure 1 Active site of natural α,β-unsaturated δ-lactones
Incorporation of fluorine into organic molecules en-
hances their biological properties,11 such as their metabolic
stability, basicity, and binding affinity (with less toxicity),12
through changes in the chemical, physical, and biological
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

B
S. K. Mandal et al.
Letter
Synlett
OsO4
2,6-lutidine
CHO
OH
Julia–Kocienski
olefination
F
F
Ph
OH
Ph
NaIO4
1,4-dioxane/H2O
CO2Et
R
O
O
R
OH
3, Cs2CO3
5a
4a
2
1
lactonization
CH2Cl2, r.t.
(E)
(E)
(Z)
CO2Et
F
F
CSA
oxidative
IIa
+
+
degradation
O
O
S
N
CO2Et
F
O
CH2Cl2, r.t.
Ph
O
O
Ph
OH
Ph
OH
IIa
+
[O]
R
OH
R
OH
S
CO2Et
F
2a
1a
5
4
3
Scheme 2 Synthesis of ethyl (2Z)-2-fluoro-5-hydroxy-5-phenylpent-2-
enoate (IIa) and 3-fluoro-6-phenyl-5,6-dihydro-2H-pyran-2-one (1a)
Scheme 1 Retrosynthetic analysis for the synthesis of 3-fluoro 6-sub-
stituted 5,6-dihydropyran-2-ones
Table 1 Screening for the Synthesis of Dihydropyranone 2a
hyde 4a, the crude product was used directly in a condensa-
tion reaction with BT-sulfone 3. Initially, the condensation
was tested with DBU in CH2Cl2 at room temperature, but
only trace amounts of the product were isolated (Table 1,
entry 1). Changing the base with CH2Cl2 or THF as solvent
(entries 2 and 3) only improved the yield to 23% with mod-
erate stereoselectivity (E/Z = 1:1.5 or 1:1.2, respectively)
and without any recovery of starting material. At this junc-
ture, we realized it was necessary to develop either the oxi-
dation conditions or the condensation reaction. A change in
the phase-transfer catalyst to TBAB gave a similar result, as
it slowed the oxidation process with residual starting mate-
rial being isolated. Changing the reaction temperature had
little effect on the yield or selectivity. To confirm the de-
composition of β-hydroxy aldehyde 4a under the reaction
conditions (Conditions A), we examined other reported
procedures.22 We were pleased to find that OsO4·NaIO4 in
the presence of 2,6-lutidine (Conditions B) provided an ex-
cellent oxidizing combination.23 Several solvent systems,
[1,4-dioxane–H2O, t-BuOH–H2O, and MeCN–H2O (1:1)]
were screened, but 1,4-dioxane–H2O was found to be opti-
mal. In terms of the yield and convenient separation, Cs2CO3
in CH2Cl2 at room temperature for the condensation with 3
(entry 4) was superior to Cs2CO3 in THF at room tempera-
ture (entry 3). The BT-sulfone remained unreacted when
K2CO3 was used as the base (entry 5). Although stereoselec-
tivity was low with the optimized conditions, the yield in-
creased slightly when the reaction was performed under a
nitrogen atmosphere (entry 6). The use of LDA at –20 °C led
to a complex mixture (entry 7). The presence of additives or
changes in the base showed little effect in improving the
yield or selectivity (entries 8 and 9). Lactonization of 2a in
the presence of camphor-10-sulfonic acid (CSA) gave lac-
tone 1a in 33% overall yield (Scheme 2). We also attempted
the conversion with the TBDMS-protected homoallyl alco-
hol 5a under our optimized conditions, but obtained only a
24% overall yield of the desired lactone 1a.
CHO
conditions
A or B
3
2a
+
IIa
Ph
OH
5a
Ph
OH
4a
base,
solvent
Entry Oxidation Base
conditionsa
Solvent
E/Zb (2a/IIa)
Yieldc
(%)
1
2
A
DBU
CH2Cl2
CH2Cl2
THF
–
trace
20
A
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
Cs2CO3
LDA
1.5:1
1.2:1
1.4:1
–
3
A
23
4
B
CH2Cl2
CH2Cl2
CH2Cl2
THF
53
5
B
NRd
62
6
Be
Bf
Bg
Bg
B
1.4:1
7
complex mixture
1.3:1
–
8
Cs2CO3
DBU
CH2Cl2
CH2Cl2
toluene
52
9
1.4:1
48
h
10
DBU
1.1:1
–
a Reaction conditions: A: NaIO4 (5 equiv), RuCl3 (1.0 mol%), TBAI (5.0
mol%), 10 M EtOAc–H2O (1:5). B: NaIO4 (4 equiv), 2,6-lutidine (2.0 equiv),
OsO4 (2.0 mol%), 10 M 1,4-dioxane–H2O (3:1).
b Ratio determined from the 1H NMR spectrum of the crude reaction mix-
ture.
c Isolated yield of the mixture of E- and Z-isomers.
d No reaction.
e Under N2.
f At –20 °C with 2.0 M LDA.
g Reaction in the presence of MgBr2.
h The product was not isolated.
To evaluate the generality of the reaction, a series of β-
hydroxy aldehydes containing either electron-rich or elec-
tron-deficient aryl rings 4a–h, were prepared and treated
with sulfone 3 under conditions B (Table 2).24,25 The ratio of
isomers was calculated by 1H NMR analysis of the crude re-
action mixture, which showed the alkene proton of the E-
isomer (m) at a lower field than the Z-isomer (dt). The
yields of the condensation products were moderate to good
for the range of β-hydroxy aldehydes 4a–h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

C
S. K. Mandal et al.
Letter
Synlett
Table 2 Screening for Synthesis of Fluoro Esters 2a
In conclusion, a new methodology has been developed
for constructing 6-substituted 3-fluoro-5,6-dihydropyran-
2-ones by using a Julia–Kocienski olefination as the key
step. Although the stereoselectivity is not high, the method
has the advantages of using mild conditions and of being
tolerant to various alcohol groups. Further studies are in
progress to extend this protocol to the construction of fluo-
rinated and non-fluorinated analogues of natural products.
3
CHO
Cs2CO3, CH2Cl2
2
+ II
R
OH
r.t., overnight
4
Entry
R
Products
Ratio E/Za (2a/IIa) Yieldb (%)
1
2
3
4
5
6
7
8
Ph
2a + IIa
2b + IIb
2c + IIc
2d + IId
2e + IIe
2f + IIf
1.4:1
2.4:1
1.8:1
2.8:1
1:1.2
1.3:1
1.6:1
2.9:1
62
67
55
68
59
67
54
63
4-MeOC6H4
3,4,5-(MeO)3C6H2
4-ClC6H4
Funding Information
This research project was funded by DST-SERB, India under the Start-
Up Research Grant (Young Scientists)-CHEMICALSCIENCES [S.O
#SB/FT/CS-192/2013].
4-FC6H4
)(
1-naphthyl
(CH2)2Ph
2g + IIg
2h + IIh
Acknowledgment
4-O2NC6H4
S.K.M. and A.S. thank DST-SERB for Research Fellowships. S.K.M. also
thanks Saldiha College, the University of Kalyani, Dr. Chattopadhyay,
and Dr. Chakraborty for support.
a Determined by 1H NMR analysis of the crude reaction mixture after the
condensation reaction.
b Yield of the isolated mixture of the E- and Z-isomers.
The separation of the lactones 1a–h from Z-isomers IIa–h
by using CH2Cl2 as an eluent was next examined. Thus, a
mixture of an E-isomer 2a–h and a Z-isomer IIa–h collected
after the condensation was lactonized26 by treatment with
CSA, and the lactone 1a–h was collected in 24–44% overall
yield (Table 3). Characterization of the lactone was carried
out by HRMS, IR, and NMR analysis. The presence of fluo-
rine was confirmed from the 13C NMR spectra, which
showed a high coupling constant (1JCF = 257.0 Hz) for the vi-
nylic carbon attached to the fluorine atom.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588534.
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References and Notes
(1) Presented at the NEHU (ETC-2016) and KU (NSCTC-VII-2016)
conference: S. K. Mandal and A. P. Chattopadhyay, An Approach
for the Synthesis of Fluorinated 6-Substituted 5,6-Dihydropy-
ran-2-one Analogues. Also presented at the VB (RTCR-2017)
conference: S. K. Mandal and A. Sarkar, Synthesis of Fluorinated
6-Substituted 5,6-Dihydropyran-2-one Analogues.
(2) (a) Cardona, W.; Quiñones, W.; Robledo, S.; Vélez, I.; Murga, J.;
García-Fortanet, J.; Carda, M.; Cardona, D.; Echeverri, F. Tetrahe-
dron 2006, 62, 4086. (b) Saeed, M.; Ilg, T.; Schick, M.; Abbas, M.;
Voelter, W. Tetrahedron Lett. 2001, 42, 7401. (c) Davies-
Coleman, M.; Rivett, D. Phytochemistry 1987, 26, 3047.
(3) Newlands, E. S.; Rustin, G. J. S.; Brampton, M. H. Br. J. Cancer
1996, 74, 648.
(4) Ohkuma, H.; Naruse, N.; Nishiyama, Y.; Tsuno, T.; Hoshino, Y.;
Sawada, Y.; Konishi, M.; Oki, T. J. Antibiot. (Tokyo) 1992, 45,
1239.
(5) Teruya, T.; Simizu, S.; Kanoh, N.; Osada, H. FEBS Lett. 2005, 579,
2463.
(6) (a) Kumar, P.; Naidu, S. V. J. Org. Chem. 2006, 71, 3935. (b) de
Fátima, A.; Kohn, L. K.; Antonio, M. A.; de Carvalho, J. E.; Pilli, R.
A. Bioorg. Med. Chem. 2006, 14, 622.
(7) Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2004, 67, 1216.
(8) Kudo, N.; Wolff, B.; Sekimoto, T.; Schreiner, E. P.; Yoneda, Y.;
Yanagida, M.; Horinouchi, S.; Yoshida, M. Exp. Cell Res. 1998,
242, 540.
Table 3 Synthesized 6-Substituted 3-Fluoro-5,6-Dihydropyran-2-ones 1
(E)
(E)
(Z)
CO2Et
F
F
+
II
CSA
+
CO2Et
F
R
O
O
R
OH
R
OH
II
CH2Cl2, r.t.
2
1
Entry
R
Yielda of 1 (%)
Overall yieldb of 1 (%)
1
2
3
4
5
6
7
8
Ph
4-MeOC6H4
93
92
86
90
92
94
89
86
33
40
24
44
24
32
26
44
3,4,5-(MeO)3C6H2
4-ClC6H4
4-FC6H4
1-naphthyl
(CH2)2Ph
4-O2NC6H4
a Yield of the product isolated from the mixture of E- and Z-isomers with
respect to the E-isomer.
(9) Lin, J.; Qiu, X.-L.; Qing, F.-L. Beilstein J. Org. Chem. 2010, 6, 37.
(10) Bonazzi, S.; Eidam, O.; Güttinger, S.; Wach, J.-Y.; Zemp, I.; Kutay,
U.; Gademann, K. J. Am. Chem. Soc. 2010, 132, 1432.
b Yield with respect to the homoallylic alcohol.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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S. K. Mandal et al.
Letter
Synlett
(11) (a) Sham, H. L.; Wideburg, N. E.; Spanton, S. G.; Kohlbrenner, W.
E.; Betebenner, D. A.; Kempf, D. J.; Norbeck, D. W.; Plattner, J. J.;
Erickson, J. W. J. Chem. Soc., Chem. Commun. 1991, 110.
(b) Thaisrivongs, S.; Schostarez, H.; Pals, D. T.; Turner, S. R.
J. Med. Chem. 1987, 30, 1837.
(12) (a) Kirsch, P. Modern Fluoroorganic Chemistry. Synthesis, Reac-
tivity, Applications; Wiley-VCH: Weinheim, 2004. (b) Rivkin, A.;
Yoshimura, F.; Gabarda, A. E.; Cho, Y. S.; Chou, T.-C.; Dong, H.;
Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 10913.
(20) (a) Li, B.; Masuda, S.; Minato, D.; Zhou, D.; Sugimoto, K.;
Nemoto, H.; Matsuya, Y. Tetrahedron 2014, 70, 3981. (b) Calata,
C.; Pfund, E.; Lequeux, T. Tetrahedron 2011, 67, 1398. (c) Ghosh,
A. K.; Banerjee, S.; Sinha, S.; Kang, S. B.; Zajc, B. J. Org. Chem.
2009, 74, 3689. (d) Zajc, B.; Kake, S. Org. Lett. 2006, 8, 4457.
(21) (a) Mandal, S. K.; Ghosh, A. K. Kumar R.; Zajc, B. Org. Biomol.
Chem. 2012, 10, 3164. (b) Chowdhury, M.; Mandal, S. K.;
Banerjee, S.; Zajc, B. Molecules 2014, 19, 4418. (c) Ayeni, D. O.;
Mandal, S. K.; Zajc, B. Tetrahedron Lett. 2013, 54, 6008.
(22) Yuasa, Y.; Shibuya, S.; Yuasa, Y. Synth. Commun. 2003, 33, 3947.
(23) Lee, K.; Kim, H.; Hong, J. Org. Lett. 2009, 11, 5202.
(24) 3-Hydroxy-3-phenylpropanal (4a); Typical Oxidation Proce-
dure
(13) (a) Smart, B. E. J. Fluorine Chem. 2001, 109, 3. (b) Lemal, D. M.
J. Org. Chem. 2004, 69, 1. (c) O’Hagan, D. Chem. Soc. Rev. 2008,
37, 308.
(14) (a) Ono, T.; Hayakawa, H.; Yasuda, N.; Uekusa, H.; Ohashi, Y. In
Current Fluoroorganic Chemistry: New Synthetic Directions, Tech-
nologies, Materials, and Biological Applications; Soloshonok, V.
A.; Mikami, K.; Yamazaki, T.; Welch, J. T.; Honek, J. F., Eds.; ACS
Symposium Series 949: Washington, 2007, Chap. 10 170.
(b) Bégué, J.-P.; Bonnet-Delpon, D. J. Fluorine Chem. 2006, 127,
992. (c) Alonso, D. A.; Fuensanta, M.; Gómez-Bengoa, E.; Nájera,
C. Adv. Synth. Catal. 2008, 350, 1823. (d) Chevrie, D.; Lequeux,
T.; Pommelet, J.-C. Tetrahedron 2002, 58, 4759. (e) Hara, S.;
Yamamoto, K.; Yoshida, M.; Fukuhara, T.; Yoneda, N. Tetrahe-
dron Lett. 1999, 40, 7815. (f) Chevrie, D.; Lequeux, T.; Demoute,
J. P.; Pazenok, S. Tetrahedron Lett. 2003, 44, 8127.
(g) Champagne, P. A.; Desroches, J.; Hamel, J.-D.; Vandamme,
M.; Paquin, J.-F. Chem. Rev. 2015, 115, 9073. (h) Yanai, H.;
Taguchi, T. Eur. J. Org. Chem. 2011, 5939.
To a solution of 1-phenylbut-3-en-1-ol (5a; 150 mg, 1.01 mmol)
in 3:1 1,4-dioxane/H2O (10 mL) at r.t. were successively added
2.5% OsO4 in t-BuOH (0.18 mL; 0.022 mmol) and 2,6-lutidine
(0.24 mL, 2.02 mmol). NaIO4 (864 mg, 4.04 mmol) was then
added in portions over 30 min, and the mixture was stirred at
r.t. for 2 h. The reaction was quenched by addition of H2O (10
mL), and the mixture was diluted with Et2O (20 mL). The layers
were separated, and the aqueous layer was extracted with Et2O
(2 × 50 mL). The organic layers were combined, washed with
H2O (2 × 25 mL) and brine (25 mL), then dried (Na2SO4), filtered,
and concentrated in vacuo to give the crude product, which was
used directly in the condensation reaction.
(25) Ethyl (2E)-2-Fluoro-5-hydroxy-5-phenylpent-2-enoate (2a)
and Ethyl (2Z)-2-Fluoro-5-hydroxy-5-phenylpent-2-enoate
(IIa); Typical Condensation Procedure
(15) Jeschke, P. ChemBioChem 2004, 5, 570.
(16) Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chem-
istry of Fluorine; Wiley: Hoboken, 2008.
Cs2CO3 (780 mg, 2.4 mmol) was added to a stirred solution of
the crude 4a and sulfone 3 (366 mg, 1.2 mmol) in CH2Cl2 (10
mL) at r.t., and the mixture was stirred overnight. The solids
were removed by filtration, and the solvent was removed in
vacuo. The crude product was purified by column chromatogra-
phy [silica gel (100–200 mesh) EtOAc/PE (4:1)] to give a mixture
of 2a and IIa; yield: 147 mg (62%)
(17) (a) Burton, D. J.; Yang, Z.-Y.; Qiu, W. Chem. Rev. 1996, 96, 1641.
(b) Barros, M. E. S. B.; Freitas, J. C. R.; Oliveira, J. M.; da Cruz, C. H.
B.; da Silva, P. B. N.; de Araújo, L. C. C.; Militão, G. C. G.; da Silva,
T. G.; Oliveira, R. A.; Menezes, P. H. Eur. J. Med. Chem. 2014, 76,
291. (c) Oliveira, J. M.; Freitas, J. C. R.; Comasseto, J. V.; Menezes,
P. H. Tetrahedron 2011, 67, 3003. (d) Nokami, J.; Anthony, L.;
Sumida, S.-I. Chem. Eur. J. 2000, 6, 2909.
(26) 3-Fluoro-6-phenyl-5,6-dihydro-2H-pyran-2-one (1a): Typical
Lactonization Procedure
(18) (a) Kocienski, P. J.; Bell, A.; Blakemore, P. R. Synlett 2000, 365.
(b) Zajc, B.; Kumar, R. Synthesis 2010, 1822. (c) Baudin, J. B.;
Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 1991, 32, 1175.
(19) (a) Paira, M.; Banerjee, B.; Jana, S.; Mandal, S. K.; Roy, S. C. Tetra-
hedron Lett. 2007, 48, 3205. (b) Mandal, S. K.; Roy, S. C. Tetrahe-
dron Lett. 2007, 48, 4131. (c) Mandal, S. K.; Roy, S. C. Tetrahedron
2008, 64, 11050. (d) Mandal, S. K.; Paira, M.; Roy, S. C. J. Org.
Chem. 2008, 73, 3823. (e) Saha, S.; Mandal, S. K.; Roy, S. C. Tetra-
hedron Lett. 2011, 52, 3128.
The mixture of 2a and IIa obtained from the condensation reac-
tion was treated with CSA (5 mg, 2 mol%) in CH2Cl2 (10 mL) at
r.t. overnight. The resulting mixture was concentrated and puri-
fied by column chromatography [silica gel (100–200 mesh),
CH2Cl2] to give a white solid; yield: 63 mg (33% overall); mp
82 °C.
IR (KBr) 1743, 1674, 1164, 769 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 2.66–2.74 (m, 1 H), 2.83–2.93 (m, 1 H), 5.54 (dd, J = 4.0,
12.0 Hz, 1 H), 6.36–6.40 (m, 1 H), 7.36–7.48 (m, 5 H). 13C NMR
3
(100 MHz, CDCl3): δ = 30.6 (d, JCF = 4.0 Hz), 80.0, 118.0 (d,
2JCF = 13.0 Hz), 126.1 (2 C), 128.9 (2 C), 129.1, 137.4, 147.6 (d,
2
1JCF = 258.0 Hz), 158.9 (d, JCF = 31.0 Hz). HRMS: m/z [M + H]
calcd for C11H10FO2: 193.0665; found: 193.0668.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D