Gold(I)-Catalyzed Tandem Cycloisomerization and Fluorination of 1,3(4)-Enyne Esters with NFSI: One-Pot Assembly of 5-Fluoro- Cyclopentenones

Article abstract of DOI:10.1002/adsc.201800701

An efficient synthetic approach for the synthesis of 5-fluoro-cyclopentenones containing a fluorine-substituted carbon stereocenter that relies on gold(I)-catalyzed cycloisomerization and fluorination sequence of 1,3(4)-enyne esters with N-fluorbenzensulfonimide (NFSI) is described. This tandem transformation exhibited a broad substrate scope and excellent functional group compatibility, providing a novel protocol for rapid assembly 5-fluoro-cyclopentenones in good to excellent yields under mild reaction conditions. The mechanistic studies revealed that the transformation involves a gold-catalyzed cycloisomerization and electrophilic fluorination cascade to give the 5-fluoro-cyclopentenones. (Figure presented.).

Full text of DOI:10.1002/adsc.201800701

Title: Gold(I)-Catalyzed Tandem Cycloisomerization and Fluorination
of 1,3(4)-Enyne Esters with NFSI: One-Pot Assembly of 5-Fluoro-
Cyclopentenones
Authors: Xianxiao Chen, Yuanyuan Zhou, Mei Hong, Yuan Ling,
Dongliang Yin, Shifa Wang, Xiaoxiang Zhang, and Weidong
Rao
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800701
Link to VoR: http://dx.doi.org/10.1002/adsc.201800701

10.1002/adsc.201800701
Advanced Synthesis & Catalysis
Very Important Publication
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Gold(I)-Catalyzed Tandem Cycloisomerization and
Fluorination of 1,3(4)-Enyne Esters with NFSI: One-Pot
Assembly of 5-Fluoro- Cyclopentenones
Xianxiao Chen, Yuanyuan Zhou, Mei Hong, Yuan Ling, Dongliang Yin, Shifa Wang,
Xiaoxiang Zhang,* and Weidong Rao*
Jiangsu Key Laboratory of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing
Forestry University, Nanjing 210037, China. e-mail: weidong@njfu.edu.cn(W. R); zhangxiaoxiang@njfu.edu.cn (X. Z);
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
cyclopentenones in good to excellent yields under mild
reaction conditions. The mechanistic studies revealed that
Abstract. An efficient synthetic approach for the synthesis
of 5-fluoro-cyclopentenones containing fluorine-
a
the
transformation
involves
a
gold-catalyzed
substituted carbon stereocenter that relies on gold(I)-
catalyzed cycloisomerization and fluorination sequence of
1,3(4)-enyne esters with N-fluorbenzensulfonimide (NFSI) is
described. This tandem transformation exhibited a broad
substrate scope and excellent functional group compatibility,
providing a novel protocol for rapid assembly 5-fluoro-
cycloisomerization and electrophilic fluorination cascade to
give the 5-fluoro-cyclopentenones.
Keywords: cycloisomerization; fluorination; 5-fluoro-
cyclopentenones; gold; enyne esters
Introduction
Fluorine-containing molecules have found a wide
range
of
applications
in
pharmaceuticals,
agrochemicals and material sciences due to their
unique physicochemical and biological properties.[1-2]
Therefore, the development of efficient synthetic
approaches for the introduction of fluorine atoms into
diverse organic frameworks has attracted increasing
attention.[3] Among various organofluorine molecules,
α-fluoroketones are of particular interest because of
their potential applications as a versatile building
blocks for the synthesis of a wide variety of bioactive
compounds such as those illustrated in Figure 1.[4]
Consequently, this has led to the establishment of a
diverse array of elegant synthetic strategies in recent
years towards its construction.[5-12] Including
nucleophilic fluorine substitution of α-haloketones or
its analogues with fluoride,[5] electrophilic
fluorination of ketones enabled by a one-step[6] or
two-step process via enolate anion, enamine or imine,
enol ether,[7] decarboxylative fluorination of β-
ketoacids,[8] fluorine insertion into α-diazocarbonyl
compounds,[9] oxidative difunctionalization of
phenylethylenes[10] and vinyl azides,[11] and other
processes.[12] Despite these advances, current reported
approaches are still limited to acyclic α-fluoroketones,
Figure 1. Selected examples of bioactive cyclic α-fluoro
ketones and its derivatives
Recently, the combination of gold catalysis with
fluorinating reagents has emerged as powerful
strategies for the incorporation of fluorine atom into
diverse molecules to deliver a number of fluorine-
containing organic complexes.[15-18] For instance,
Nevado's group developed a novel and efficient
protocol for the preparation of α-fluoro ketones or
acetals through an alkoxylation-fluorination of
alkynes by merging gold catalysis with Selectfluor
(Scheme 1a).[16] Very recently, Xu and co-workers
have elegantly demonstrated that α-fluoro ketones
could be accessed by insertion of HF into the gold
carbene, which was generated in-situ from N-oxides
and the synthesis of cyclic α-fluoroketones bearing a
[13]
fluorine-substituted carbon stereocenter
from
acyclic precursors remains largely elusive.[14]
1
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10.1002/adsc.201800701
Advanced Synthesis & Catalysis
Table.1 Optimization of Reaction Conditions[a]
and alkynes in the presence of gold catalyst (Scheme
1b). [9a, d] Nevado and Gouverneur have shown that α-
fluoroenones can be synthesized from propargylic
esters with Selectfluor under gold(I) catalysis, albeit
the mechanism involved remains obscure (Scheme
1c).[17]
A
one-pot, two-step process for the
preparation of α-fluoroenones from allenyl carbinol
esters has been realized by using gold(I) catalyst with
Selectfluor (Scheme 1d).[18] Inspired by these seminal
works and as part of ongoing efforts in the field of
gold catalysis,[19] we turned our attention to explore
the reactivity of 1,3(4)-enyne esters in the presence of
the electrophilic fluorinating reagents such as N-
fluorbenzensulfonimide (NFSI) (Scheme 1e).[20-23]
We envisioned that the in-situ generated
cyclopentadiene species 3 through a gold-catalyzed
cycloisomerization of 1,3(4)-enyne esters 1 might
undergo further electrophilic fluorination to afford
the desired α-fluoro-cyclopentenone derivatives.
Herein, we disclose the details of this chemistry that
provides expedient and regioselective access to 5-
fluoro-cyclopentenones bearing a fluorine-substituted
carbon stereocenter from simple and readily available
1,3(4)-enyne esters with N-fluorbenzensulfonimide
(NFSI) in one-pot operation.
Yield [%]
2a 3a 4a
Entry
Solvent
DCE
[Au]
[F]
1
2
3
4
5
6
7
8
NFSI
NFSI
NFSI
NFSI
NFSI
SelectFluor
NFPYBF4
28
-
-
-
53
50
-
A
A
A
A
A
A
A
A
B
C
D
A
toluene 29
[b]
CH3CN
-
-
MTBE 86
THF
MTBE
MTBE
81
-
-
-
-
-
95
93
89
-
-
-
-
-
-
-
-
-
-
Me3NFPYBF4 MTBE
9
NFSI
NFSI
NFSI
NFSI
MTBE 83
MTBE 81
MTBE 62
MTBE 79
10
11
12[c]
-
[a]All reactions were performed with 1 (0.3 mmol), gold(I)
complex A (2 mol %) and [F] source (0.6 mmol) in solvent
(6 mL) at room temperature for 24 h. [b]No reaction.
[c]Reaction performed with NFSI (0.45 mmol, 1.5 equiv).
presence of electrophilic fluorinating reagents to
establish the optimum reaction conditions (Table
1).[24] This initially revealed that treating 1a with 2
mol% of gold(I) phosphine catalyst A[24a] and NFSI
(2 equiv.) in 1,2-dichloroethane at room temperature
for 24 h afforded 5-fluorinated cyclopentenone 2a
and 4a in 28% and 53% yields, respectively (Table 1,
entry 1). The structure of 5-fluorinated
cyclopentenone 2a was unambiguously ascertained
by NMR measurements and X-ray crystallographic
analysis.[25] A similar results were observed upon
repeating the reaction in toluene instead of 1,2-
dichloroethane as the solvent (entry 2). However,
switching the solvent to CH3CN was found to result
1
in no reaction observed based on TLC and H NMR
analysis (entry 3). Gratifyingly, we found that the
reaction proceeded efficiently, leading to the desired
5-fluorinated cyclopentenone 2a as the sole product
in 86% and 81% yields and without the formation of
3a and 4a upon changing the solvent from DCE to
MTBE and THF (entries 4-5). On the contrary, only
cyclopentadiene 3a was obtained in 89-95% yields
when other commercially fluorinating reagents such
as Selectfluor, NFPYBF4 and Me3NFPYBF4 were
used (entries 6-8). It was then found that replacement
Scheme 1. Synthesis of α-fluoroketones by merging gold
catalysis and fluorinating reagents
Results and Discussion
We began our studies by examining the gold-
catalyzed cycloisomerization and electrophilic
fluorination cascade of 1,3-enyne ester 1a in the
of gold(I) complex A with gold(I) complex B,[24b]
C
[24c] and PPh3AuNTf2[24d] gave the product 2a in lower
yields (entries 9-11). In addition, using 1.5
equivalents instead of 2 equivalents of NFSI gave the
2
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10.1002/adsc.201800701
Advanced Synthesis & Catalysis
product 2a in 79% yield (entry 12). On the basis of
the above results, reaction of 1a with NFSI (2 equiv)
in the presence of 2 mol% of gold(I) phosphine
catalyst A in MTBE at room temperature for 24 h
was deemed to provide the optimum conditions.
cycloisomerization and fluorination cascade reaction
to afford the corresponding 5-fluoro-cyclopentenone
2y in good yield.
With the optimal conditions in hand, we set out to
evaluate the generality of the present protocol with a
variety of 1,3-enyne acetates, and the results are
summarized in Scheme 2. Overall, the tandem
reaction conditions were found to be broad, providing
a
diverse array of 5-fluoro-cyclopentenone
derivatives bearing a fluorine-substituted carbon
stereocenter with a variety of substitution patterns in
65-93% yield from the corresponding substrates 1a-w.
Substrates containing a linear or cyclic alkyl groups
such as cyclohexyl at the R2 position were found to
proceed well under the optimal conditions, affording
the products 2b, 2c and 2d in 87%, 90% and 93%
yields, respectively. Pleasingly, substrates bearing a
variety of functional groups such as phenyl ether (1e),
esters (1f, g), ketone (1h), sulfonamide (1i),
phthalimide (1j), weinreb or indoline amides (1k, l)
were proven to be compatible with this tandem
process, providing the corresponding fluorinated
products 2e-l in 66-88% yields. Likewise, 1,3-enyne
acetates having electron-donating (1m-n) as well as
electron-withdrawing (1o-q) substituents at para-
position of the phenyl moiety were well tolerated and
furnished the desirable products 2m-q in excellent
yields. Similarly, the reaction of 1r and 1s containing
a 1-naphthyl or 2-naphthyl group at the R1 position
furnished 2r and 2s in 85% and 88% yields,
respectively. Furthermore, our protocol is not
restricted to the substrates of 1,3-enyne acetates with
aryl substituents at R1 position and can be applied to
the substrates of aliphatic substituents at both R1and
R2 positions as well. For instance, 1t and 1u were
smoothly converted to the corresponding fluorinated
products 2t-u in 62-71% yields. Additionally, the
tandem reactions of 1,3-enyne acetates incorporating
cyclic alkenes such as cyclohexene (1v) and
cycloheptene (1w) produced the fluorinated bicyclic
cyclopentenones 2v and 2w in 65% and 68% yields.
It is noteworthy that a gram-scale reaction of 1a (5
mmol, 1.07 g) with NFSI in the presence of 1 mol%
gold(I) catalyst A was also successful and provided
2a in a slightly diminished yield of 75% (0.71 g),
demonstrating the scalability and practicality of the
present protocol.
Scheme 2. Gold(I)-catalyzed tandem cycloisomerization
and fluorination of 1,3-enyne esters 1a-w with NFSI. All
reactions were performed with 1(0.3 mmol), gold(I)
complex A (2 mol %) and NFSI (0.6 mmol) in MTBE (6
mL) at room temperature for 24 h. [a]The reactions was
conducted on 5.0 mmol scale with 1 mol% of gold(I)
complex A.
Encouraged by the above success, we next turned
our attention to examine whether the present protocol
could also be applied to 1,4-enyne acetates, which the
cycloisomerization chemistry has been well
[23]
documented.
Gratifyingly, the present approach
could be applied to 1,4-enyne acetates, allowed for
the regiospecific construction of 5-fluoro-
cyclopentenones containing a fluorine-substituted
carbon stereocenter in satisfactory yields with a
variety of substitution patterns (Scheme 3). Notably,
it was found that the 1,4-enyne acetates with a
cyclohexyl substitution at the alkyne terminus, was
Scheme 3. Gold(I)-catalyzed tandem cycloisomerization
and fluorination of 1,4-enyne esters 1x-α with NFSI. All
reactions were performed with 1(0.3 mmol), gold(I)
complex A (2 mol %) and NFSI (0.6 mmol) in MTBE (6
mL) at room temperature for 24 h.
also
compatible
in
the
gold(I)-catalyzed
3
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10.1002/adsc.201800701
Advanced Synthesis & Catalysis
The isolation of 4a and 3a under certain conditions
described in Table 1 led us to evaluate on their
possible involvement as intermediates in this tandem
process. To support this hypothesis and gain more
insight into the reaction mechanism, several control
experiments were performed as described in Scheme
4. First, subjecting 3a with NFSI in MTBE in the
presence and absence of the gold(I) catalyst A (2
mol%) at room temperature for 24 h provided the
desired product 2a in respective yields of 88% and 91%
(Scheme 4, eq 1). We next investigated the analogous
reaction of 4a and NFSI under the above mentioned
conditions. These experiments showed that there was
no formation of 5-fluorinated cyclopentenone 2a by
Scheme 5. Proposed mechanism
Conclusion
1
TLC and H NMR analysis, and starting material 4a
In summary, we have developed an efficient
protocol for the synthesis of 5-fluorocyclopentenone
possessing a fluorine-substituted carbon stereocenter
from gold(I)-catalyzed cycloisomerization and
fluorination sequence of 1,3(4)-enyne esters with
NFSI under mild reaction conditions in one-pot
operation. The present fluorination methodology also
exhibited high regioselectivity and excellent
functional group compatibility. Efforts to explore the
synthetic applications of the one-pot fluorination
reactions are currently underway and will be reported
in due course.
were recovered in near quantitative yield in both
cases (Scheme 4, eq 2). These results clearly
indicated that cyclopentenone 4a was not the
productive intermediate and the formation of
cyclopentadiene 3a intermediate must be involved in
this transformation.
Experimental Section
Representative Experimental Procedure for Gold(I)
Complex A-Catalyzed Tandem Cycloisomerization and
Fluorination of 1,3(4)-Enyne Esters with NFSI
To a solution of 1,3(4)-enyne acetate 1 (0.3 mmol) and
NFSI (0.36 mmol) in MTBE (6 mL) was added gold(I)
complext A (2 mol%) under an argon atmosphere. The
reaction mixture was stirred at room temperature for 12-24
h. Upon completion, the solvent was removed under
reduced pressure. Purification by flash column
chromatography on silica gel (petroleum ether:EtOAc
=50:1 as eluent) furnished the product 2a.
Scheme 4. Control Experiments
On the basis of the above results and the literature
precedents,[22] a plausible mechanism for the gold(I)-
catalyzed 1,3(4)-enyne ester cycloisomerization and
fluorination reaction in the presence of NFSI is
illustrated in Scheme 5. With 1,3-enyne ester 1a as a
representative example, this initially involves a gold-
catalyzed 1,3-acyloxy migration/Nazarov cyclization
to produce the cyclopentadiene 3a.[22] The resulting
electron-rich cyclopentadiene intermediate 3a may
then undergo a direct, nongold-catalyzed electrophilic
fluorination with NFSI to afford the allylic cation
species Ia or its resonance structure Ia'. Upon
hydrolysis with trace amounts of H2O from the
reaction media MTBE would furnish 5-fluoro-
cyclopentenone 2a. The formation of 5-fluoro-
cyclopentenone 2x-α from 1,4-enyne ester 1x-α could
be derived from the initially Rautenstrauch
5-Fluoro-5-methyl-3-phenylcyclopent-2-en-1-one (2a):
1
Yield: 86% (49 mg), colorless solid, mp 105-107 °C; H
NMR (400 MHz, CDCl3) δ = 7.67-7.65 (m, 2H), 7.55-7.46
(m, 3H), 6.58 (m, 1H), 3.41-3.30 (ddd, 1H, J = 19.8, 18.0,
1.6 Hz), 3.20-3.12 (ddd, 1H, J = 12.0, 10.4, 1.7 Hz), 1.61
(d, 3H, J = 22.8 Hz); 13C NMR (100 MHz, CDCl3) δ =
202.9 (d, 1C, J = 18.2 Hz), 169.9 (d, 1C, J = 3.3 Hz), 133.1,
132.1, 129.1, 127.1, 123.7, 93.9 (d, 1C, J = 182.0 Hz), 42.3
(d, 1C, J = 25.0 Hz), 21.6 (d, 1C, J = 27.0 Hz); 19F NMR
(376 MHz, CDCl3) δ = –150.2 (s); HRMS (ESI) calcd for
C12H11FONa [M+Na]+: 213.0686, found: 213.0692.
5-Fluoro-5-octyl-3-phenylcyclopent-2-en-1-one
(2b):
1
Yield: 87% (75 mg), pale-yellow solid, mp 58-60 °C; H
NMR (400 MHz, CDCl3) δ = 7.68-7.65 (m, 2H), 7.55-7.46
(m, 3H), 6.59 (d, 1H, J = 1.3 Hz), 3.25 (dd, 1H, J = 4.8,
1.7 Hz), 3.21 (d, 1H, J = 1.7 Hz), 2.05-1.95 (m, 1H), 1.84-
1.68 (m, 1H), 1.52-1.15 (m, 12H), 0.87 (t, 3H, J = 6.9 Hz);
13C NMR (100 MHz, CDCl3) δ = 203.3 (d, 1C, J = 18.2
Hz), 170.3, 133.1, 132.1, 129.1, 127.1, 124.4, 96.2 (d, 1C,
J = 183.0 Hz), 40.2 (d, 1C, J = 25.0 Hz), 34.9 (d, 1C, J =
24.0 Hz), 31.8, 29.8, 29.3, 29.1, 23.0 (d, J = 6.1 Hz), 22.6,
14.1; 19F NMR (376 MHz, CDCl3) δ = –154.9 (s); HRMS
(ESI) calcd for C19H26FO [M+H]+: 289.1962, found:
289.1976.
rearrangement[26]
fluorination
followed
and hydrolysis. However, the
formation of unfluorinated
by
electrophilic
competitive
cyclopentenone 4a could be due to protonolysis of
cyclopentadiene 3a.[22e]
4
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10.1002/adsc.201800701
Advanced Synthesis & Catalysis
5-Fluoro-3-phenyl-5-(3-phenylpropyl)cyclopent-2-en-1-
one (2c): Yield: 90% (80 mg), colorless solid, mp 88-
90 °C; 1H NMR (600 MHz, CDCl3) δ = 7.68-7.66 (m, 2H),
7.59-7.47 (m, 3H), 7.31-7.28 (m, 2H), 7.24-7.16 (m, 3H),
6.60 (d, 1H, J = 1.2 Hz), 3.30-3.17 (m, 2H), 2.75-2.65 (m,
2H), 2.13-2.03 (m, 1H), 1.92-1.71 (m, 3H); 13C NMR (100
MHz, CDCl3) δ = 203.0 (d, 1C, J = 18.2 Hz), 170.3 (d, 1C,
1.7 Hz), 3.00 (t, 2H, J = 7.2 Hz), 2.07 (ddd, 1H, J = 25.1,
13.4, 4.8 Hz), 1.92-1.75 (m, 3H), 1.66-1.48 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ = 203.1, 199.9, 170.5, 136.9,
133.1, 133.0, 132.2, 129.1, 128.6, 128.0, 127.2, 124.3, 95.9
(d, 1C, J = 184.9 Hz), 40.2 (d, 1C, J = 25.3 Hz), 38.1, 34.7
(d, 1C, J = 24.7 Hz), 24.2, 22.7 (d, 1C, J = 6.0 Hz); 19F
NMR (376 MHz, CDCl3) δ = –155.4 (s); HRMS (ESI)
J = 3.4 Hz), 141.5, 133.0, 132.2, 129.1, 128.4, 127.1, 126.0, calcd for C22H22FO2 [M+H]+: 337.1598, found: 337.1606.
124.3, 96.0 (d, 1C, J = 184.8 Hz), 40.2 (d, 1C, J = 25.4
Hz), 35.9, 34.4 (d, 1C, J = 24.8 Hz), 24.9 (d, 1C, J = 5.8
N-(3-(1-Fluoro-2-oxo-4-phenylcyclopent-3-en-1-
Hz); 19F NMR (564 MHz, CDCl3) δ = –155.1 (s); HRMS
yl)propyl)-4-methyl-N-phenylbenzenesulfonamide (2i):
(ESI) calcd for C20H19FONa [M+Na]+: 317.1312, found:
1
Yield: 86% (120 mg), colorless solid, mp 134-136 °C; H
317.1307.
NMR (400 MHz, CDCl3) δ = 7.68-7.61 (m, 2H), 7.59-7.43
(m, 5H), 7.32-7.25 (m, 5H), 7.06-7.03 (m, 2H), 6.56 (d, 1H,
5-Cyclohexyl-5-fluoro-3-phenylcyclopent-2-en-1-one
J = 1.2 Hz), 3.61 (t, 2H, J = 6.8 Hz), 3.26-3.06 (m, 2H),
2.44 (s, 3H), 2.15-2.00 (m, 1H), 1.97-1.79 (m, 1H), 1.78-
1.60 (m, 2H); 13C NMR (100 MHz, CDCl3) δ = 202.6 (d,
1C, J = 18.3 Hz), 170.3 (d, 1C, J = 3.0 Hz), 143.4, 138.9,
135.0, 132.9, 132.2, 129.4, 129.1, 128.7, 128.0, 127.7,
127.1, 124.1, 95.7 (d, 1C, J = 185.0 Hz), 50.3, 40.3 (d, 1C,
J = 25.0 Hz), 31.8 (d, 1C, J = 25.0 Hz), 22.0 (d, 1C, J = 5.1
Hz), 21.5; 19F NMR (376 MHz, CDCl3) δ = –157.1 (s);
HRMS (ESI) calcd for C27H26FNO3SNa [M+Na]+:
(2d): Yield: 93% (72 mg), pale-yellow solid, mp 118-
1
120 °C; H NMR (400 MHz, CDCl3) δ = 7.69-7.66 (m,
2H), 7.55-7.46 (m, 3H), 6.59 (d, 1H, J = 1.2 Hz), 3.29-3.21
(ddd, 1H, J = 18.3, 11.4, 1.7 Hz), 3.14-3.03 (ddd, 1H, J =
22.8, 18.3, 1.8 Hz), 2.16-2.04 (qd, 1H, J = 10.7, 3.2 Hz),
2.00 (d, 1H, J = 12.6 Hz), 1.82 (dd, 1H, J = 12.9, 1.8 Hz),
1.70 (d, 2H, J = 11.0 Hz), 1.49 (d, 1H, J = 12.8 Hz), 1.36-
1.07 (m, 4H), 0.89 (qd, 1H, J = 12.5, 3.2 Hz); 13C NMR
(100 MHz, CDCl3) δ = 203.9 (d, 1C, J = 18.0 Hz), 170.9 (d, 486.1510, found: 486.1507.
1C, J = 3.5 Hz), 133.1, 132.1, 129.1, 127.1, 125.2, 98.2 (d,
1C, J = 184.0 Hz), 42.1 (d, 1C, J = 23.0 Hz), 37.6 (d, 1C, J
2-(3-(1-Fluoro-2-oxo-4-phenylcyclopent-3-en-1-
= 26.0 Hz), 26.4 (d, 1C, J = 9.0 Hz), 26.3, 26.1 (d, 1C, J =
3.0 Hz), 25.7, 25.6; 19F NMR (376 MHz, CDCl3) δ = –
156.6 (s); HRMS (ESI) calcd for C17H19FONa [M+Na]+:
281.1312, found: 281.1305.
yl)propyl)isoindoline-1,3-dione (2j): Yield: 83% (91 mg),
colorless solid, mp 141-143 °C; 1H NMR (400 MHz,
CDCl3) δ = 7.84-7.81 (m, 2H), 7.76-7.67 (m, 2H), 7.67-
7.59 (m, 2H), 7.56-7.40 (m, 3H), 6.57 (d, 1H, J = 1.2 Hz),
3.82- 3.67 (m, 2H), 3.31-3.14 (m, 2H), 2.14-2.03 (m, 1H),
1.98-1.73 (m, 3H); 13C NMR (100 MHz, CDCl3) δ = 202.4
(d, 1C, J = 200.0 Hz), 170.2 (d, 1C, J = 3.0 Hz), 168.3,
5-Fluoro-5-(3-phenoxypropyl)-3-phenylcyclopent-2-en-
1-one (2e): Yield: 88% (82 mg), pale-yellow solid, mp
105-107 °C; 1H NMR (400 MHz, CDCl3) δ = 7.74-7.66 (m, 134.0, 132.9, 132.2, 132.0, 129.1, 127.1, 124.2, 123.2, 95.5
2H), 7.61-7.48 (m, 3H), 7.35-7.23 (m, 2H), 7.01-6.94 (m,
1H), 6.90 (dd, 2H, J = 8.7, 0.9 Hz), 6.64 (d, 1H, J = 1.3
Hz), 4.12-3.97 (m, 2H), 3.33 (dd, 1H, J = 4.6, 1.7 Hz),
3.29 (d, 1H, J = 1.7 Hz), 2.30-2.17 (m, 1H), 2.12-1.92 (m,
3H); 13C NMR (100 MHz, CDCl3) δ = 202.8 (d, 1C, J =
18.2 Hz), 170.4 (d, 1C, J = 3.4 Hz), 158.8, 133.1, 132.3,
129.5, 129.2, 127.2, 124.3, 120.8, 114.5, 95.9 (d, 1C, J =
185.3 Hz), 67.3, 40.4 (d, 1C, J = 25.2 Hz), 31.7 (d, 1C, J =
25.2 Hz), 23.2 (d, 1C, J = 5.7 Hz); 19F NMR (376 MHz,
(d, 1C, J = 185.8 Hz), 40.2 (d, 1C, J = 25.2 Hz), 37.8, 32.3
(d, 1C, J = 25.3 Hz), 22.5 (d, 1C, J = 5.5 Hz); 19F NMR
(376 MHz, CDCl3) δ = –156.3 (s); HRMS (ESI) calcd for
C22H18FNO3Na [M+Na]+: 386.1163, found: 396.1163.
4-(1-Fluoro-2-oxo-4-phenylcyclopent-3-en-1-yl)-N-
methoxy-N-methylbutanamide (2k): Yield: 66% (61 mg),
pale-yellow oil; 1H NMR (400 MHz, CDCl3) δ = 7.74-7.60
(m, 2H), 7.58-7.40 (m, 3H), 6.58 (d, 1H, J = 1.2 Hz), 3.67
(s, 3H), 3.37-3.22 (m, 2H), 3.16 (s, 3H), 2.60-2.43 (m, 2H),
2.11-1.98 (m, 1H), 1.89-1.70 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ = 203.0 (d, 1C, J = 18.2 Hz), 170.7 (d, 1C, J =
3.3 Hz), 133.0, 132.2, 129.1, 127.2, 124.2, 96.0 (d, 1C, J =
183.0 Hz), 61.2, 40.0 (d, 1C, J = 25.0 Hz), 34.1 (d, 1C, J =
25.0 Hz), 32.1, 31.4, 18.1 (d, J = 6.4 Hz); 19F NMR (376
MHz, CDCl3) δ = –155.4 (s); HRMS (ESI) calcd for
C17H20FNO3Na [M+Na]+: 328.1319, found: 328.1328.
CDCl3)
δ = –156.4 (s); HRMS (ESI) calcd for
C20H19FO2Na [M+Na]+: 333.1261, found:333.1269.
3-(1-Fluoro-2-oxo-4-phenylcyclopent-3-en-1-yl)propyl
acetate (2f): Yield: 83% (69 mg), pale-yellow solid, mp
1
71-72 °C; H NMR (400 MHz, CDCl3) δ = 7.69-7.62 (m,
2H), 7.56-7.44 (m, 3H), 6.59 (d, 1H, J = 1.3 Hz), 4.17-4.02
(m, 2H), 3.34-3.13 (m, 2H), 2.16-1.97 (m, 4H), 1.87-1.73
(m, 3H); 13C NMR (100 MHz, CDCl3) δ = 202.6 (d, 1C, J
= 18.4 Hz), 171.0, 170.3 (d, 1C, J = 3.2 Hz), 132.9, 132.3,
129.1, 127.1, 124.2, 95.6 (d, 1C, J = 185.5 Hz), 64.0, 40.2
(d, 1C, J = 25.3 Hz), 31.5 (d, 1C, J = 25.2 Hz), 22.5 (d, 1C,
J = 5.7 Hz), 20.9; 19F NMR (376 MHz, CDCl3) δ = –156.6
(s); HRMS (ESI) calcd for C16H18FO3 [M+H]+: 277.1234,
found: 277.1219.
5-Fluoro-5-(4-(indolin-1-yl)-4-oxobutyl)-3-
phenylcyclopent-2-en-1-one (2l): Yield: 71% (77 mg),
1
brown solid, mp 119-121 °C; H NMR (400 MHz, CDCl3)
δ = 8.19 (d, 1H, J = 8.3 Hz), 7.68 (dd, 2H, J = 8.1, 1.4 Hz),
7.57-7.43 (m, 3H), 7.17 (t, 2H, J = 6.7 Hz), 7.00 (t, 1H, J =
7.4 Hz), 6.60 (d, 1H, J = 1.2 Hz), 4.04 (t, 2H, J = 8.5 Hz),
3.44-3.26 (m, 2H), 3.20 (t, 2H, J = 8.5 Hz), 2.59-2.44 (m,
2H), 2.14-2.08 (m, 1H), 1.96-1.83 (m, 3H); 13C NMR (100
MHz, CDCl3) δ = 203.0 (d, 1C, J = 18.0 Hz), 170.6 (d, 1C,
J = 41.2 Hz), 142.9, 133.0, 132.2, 131.0, 129.1, 127.5,
127.2, 124.5, 124.2, 123.6, 116.9, 96.1 (d, 1C, J = 184.4
Hz), 47.9, 40.0 (d, 1C, J = 25.3 Hz), 35.4, 34.1 (d, 1C, J =
24.7 Hz), 28.0, 18.2 (d, 1C, J = 6.2 Hz); 19F NMR (376
MHz, CDCl3) δ = –155.2 (s); HRMS (ESI) calcd for
Ethyl
4-(1-fluoro-2-oxo-4-phenylcyclopent-3-en-1-
yl)butanoate (2g): Yield: 87% (76 mg), pale-yellow solid,
1
mp 40-42 °C; H NMR (400 MHz, CDCl3) δ = 7.68-7.65
(m, 2H), 7.58-7.43 (m, 3H), 6.59 (d, 1H, J = 1.3 Hz), 4.11
(q, 2H, J = 7.1 Hz), 3.28 (d, 1H, J = 1.7 Hz), 3.24 (t, 1H, J
= 1.9 Hz), 2.48-2.30 (m, 2H), 2.08-2.00 (m, 1H), 1.90-1.61
(m, 3H), 1.24 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz,
CDCl3) δ = 202.7 (d, 1C, J = 18.1 Hz), 173.1, 170.5 (d, 1C, C23H22FNO2Na [M+Na]+: 386.1527, found: 386.1519.
J = 3.3 Hz), 133.0, 132.2, 129.1, 127.1, 124.2, 95.8 (d, 1C,
J = 180.0Hz), 60.4, 40.1(d, 1C, J = 25.0Hz), 34.2, 33.9,
5-Fluoro-5-methyl-3-(p-tolyl)cyclopent-2-en-1-one
18.5 (d, 1C, J = 6.2 Hz), 14.2; 19F NMR (376 MHz,
1
(2m): Yield: 84% (52 mg), yellow solid, mp 90-92 °C; H
NMR (400 MHz, CDCl3): δ = 7.55 (d, 2H, J = 8.2 Hz),
7.28 (d, 2H, J = 8.0 Hz), 6.54 (d, 1H, J = 1.3 Hz), 3.38-
3.28(ddd, 1H, J = 19.7, 18.0, 1.6 Hz), 3.18-3.10 (ddd, 1H,
J = 18.0, 10.4, 1.7 Hz), 2.42 (s, 3H), 1.60 (d, J = 22.8 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ = 203.0 (d, 1C, J =
18.3 Hz), 170.0, 143.0, 130.4, 129.8, 127.1, 122.9, 94.0 (d,
1C, J = 182.8 Hz), 42.3 (d, 1C, J = 25.1 Hz), 21.7 (d, 1C, J
= 27.0 Hz), 21.6; 19F NMR (376 MHz, CDCl3): δ = –150.1
CDCl3) δ= –155.9 (s); HRMS (ESI) calcd for C17H20FO3
[M+H]+: 291.1391, found: 291.1384.
5-fluoro-5-(5-oxo-5-phenylpentyl)-3-phenylcyclopent-2-
en-1-one (2h): Yield: 68% (69 mg), colorless solid, mp
1
82-83 °C; H NMR (400 MHz, CDCl3) δ = 7.95-7.93 (m,
2H), 7.67-7.65 (m, 2H), 7.57-7.43 (m, 6H), 6.59 (d, 1H, J
= 1.2 Hz), 3.26 (dd, 1H, J = 4.3, 1.7 Hz), 3.22 (d, 1H, J =
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800701
Advanced Synthesis & Catalysis
(s); HRMS (ESI) calcd for C13H13FONa [M+Na]+:
227.0843, found: 227.0851.
130.5, 129.1, 128.9, 128.3, 127.8, 127.6, 127.1, 124.0,
123.7, 94.0 (d, 1C, J = 183.1 Hz), 42.4 (d, 1C, J = 25.2 Hz),
21.7 (d, 1C, J = 27.0 Hz); 19F NMR (565 MHz, CDCl3) δ =
–149.8 (s); HRMS (ESI) calcd for C16H13FONa [M+Na]+:
263.0843, found: 263.0836.
3-([1,1'-Biphenyl]-4-yl)-5-fluoro-5-methylcyclopent-2-
en-1-one (2n): Yield: 79% (63 mg), colorless solid, mp
142-144 °C; 1H NMR (400 MHz, CDCl3) δ = 7.75-7.70 (m,
4H), 7.65-7.63 (m, 2H), 7.53-7.46 (m, 2H), 7.44-7.40 (m,
1H), 6.63 (d, 1H, J = 1.3 Hz), 3.44-3.34 (ddd, 1H, J = 21.5,
18.0, 1.6 Hz), 3.24-3.16 (ddd, 1H, J = 18.0, 10.4, 1.7 Hz),
1.63 (d, 3H, J = 22.8 Hz); 13C NMR (100 MHz, CDCl3) δ
= 202.9 (d, 1C, J = 18.8 Hz), 169.5, 144.9, 139.6, 131.9,
129.0, 128.3, 127.7, 127.6, 127.1, 123.5, 94.0 (d, 1C, J =
182.9 Hz), 42.3 (d, 1C, J = 25.2 Hz), 21.7 (d, 1C, J = 26.9
Hz); 19F NMR (376 MHz, CDCl3) δ = –150.1(s); HRMS
(ESI) calcd for C18H15FONa [M+Na]+: 289.0999, found:
289.0994.
Ethyl 4-(4-cyclopropyl-1-fluoro-2-oxocyclopent-3-en-1-
1
yl)butanoate (2t): Yield: 71% (54 mg), colorless oil; H
NMR (400 MHz, CDCl3) δ = 5.91 (d, 1H, J = 1.4 Hz), 4.09
(q, 2H, J = 7.1 Hz), 2.62 (dd, 2H, J = 15.6, 1.4 Hz), 2.40-
2.24 (m, 2H), 1.95 -1.81 (m, 2H), 1.75-1.55 (m, 3H), 1.22
(t, 3H, J = 7.1 Hz), 1.14-1.09 (m, 2H), 0.96-0.86 (m, 2H);
13C NMR (100 MHz, CDCl3) δ = 202.3 (d, 1C, J = 18.1
Hz), 182.7 (d, 1C, J = 3.3 Hz), 173.1, 124.3, 95.5 (d, 1C, J
= 184.9 Hz), 60.4, 39.6 (d, 1C, J = 25.1 Hz), 33.9, 33.8 (d,
1C, J = 24.0 Hz), 18.5 (d, 1C, J = 6.4 Hz), 15.3, 14.2, 10.5,
10.0; 19F NMR (376 MHz, CDCl3) δ = –157.0 (s); HRMS
(ESI) calcd for C14H20FO3 [M+H]+: 255.1391, found:
255.1384.
5-Fluoro-3-(4-fluorophenyl)-5-methylcyclopent-2-en-1-
one (2o): Yield: 81% (51 mg), colorless solid, mp 120-
1
122 °C; H NMR (400 MHz, CDCl3) δ = 7.71-7.62 (m,
2H), 7.22-7.13 (m, 2H), 6.53 (d, 1H, J = 1.3 Hz), 3.40-3.25
(ddd, 1H, J = 19.8, 18.0, 1.7 Hz), 3.17-3.09 (ddd, 1H, J =
18.0, 10.5, 1.7 Hz), 1.61 (d, 3H, J = 22.8 Hz); 13C NMR
Ethyl 4-(4-cyclohexyl-1-fluoro-2-oxocyclopent-3-en-1-
1
yl)butanoate (2u): Yield: 62% (55 mg), colorless oil; H
NMR (400 MHz, CDCl3) δ = 5.91 (t, 1H, J = 1.1 Hz), 4.10
(100 MHz, CDCl3) δ = 202.7 (d, 1C, J = 18.4 Hz), 168.5 (d, (q, 2H, J = 7.1 Hz), 2.84-2.73 (m, 2H), 2.39-2.22 (m, 2H),
1C, J = 3.4 Hz), 165.0 (d, 1C, J = 253.0 Hz), 129.5 (d, 1C,
J = 2.6 Hz), 129.3 (d, 1C, J = 8.9 Hz), 123.5, 116.4 (d, 1C,
J = 22.0 Hz), 93.9 (d, 1C, J = 183.2 Hz), 42.4 (d, 1C, J =
25.2 Hz), 21.6 (d, 1C, J = 26.9 Hz); 19F NMR (376 MHz,
CDCl3) δ –106.2 (s), –149.9 (s); HRMS (ESI) calcd for
C12H11F2O [M+H]+: 209.0772, found: 209.0775.
1.94-1.57 (m, 9H), 1.39-1.13 (m, 9H); 13C NMR (100 MHz,
CDCl3) δ = 203.6 (d, 1C, J = 18.2 Hz), 184.4, 173.1, 125.1,
95.6 (d, 1C, J = 185.1 Hz), 60.4, 42.0, 40.9 (d, 1C, J = 24.5
Hz), 34.0, 33.9, 33.8, 30.8, 30.7, 25.9, 25.8 (d, 1C, J = 2.3
Hz), 18.6 (d, 1C, J = 6.4 Hz), 14.2; 19F NMR (376 MHz,
CDCl3) δ = –158.0 (s); HRMS (ESI) calcd for C17H26FO3
[M+H]+: 297.1860, found: 297.1871.
3-(4-Chlorophenyl)-5-fluoro-5-methylcyclopent-2-en-1-
one (2p): Yield: 87% (59 mg), colorless solid, mp 85-
87 °C; 1H NMR (400 MHz, CDCl3) δ = 7.66-7.54 (m, 2H),
7a-Fluoro-3-phenyl-3a,4,5,6,7,7a-hexahydro-1H-inden-
1-one (2v): Yield: 65% (45 mg), pale-yellow solid, mp 49-
7.50-7.41 (m, 2H), 6.57 (d, 1H, J = 1.3 Hz), 3.44-3.24 (ddd, 50 °C; 1H NMR (400 MHz, CDCl3) δ = 7.65-7.58 (m, 2H),
1H, J = 19.8, 18.1, 1.8 Hz), 3.16-3.09 (ddd, 1H, J = 18.0,
10.5, 1.7 Hz), 1.61 (d, J = 22.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ = 202.7 (d, 1C, J = 26.9 Hz), 168.4 (d, 1C,
J = 3.4 Hz), 138.4, 131.6, 129.5, 128.3, 124.1, 93.8 (d, 1C,
J = 183.3 Hz), 42.3 (d, 1C, J = 25.3 Hz), 21.6 (d, 1C, J =
26.9 Hz); 19F NMR (376 MHz, CDCl3) δ = –150.0 (s);
HRMS (ESI) calcd for C12H1035ClFONa [M+Na]+:
247.0296, found: 247.0287.
7.52-7.43 (m, 3H), 6.47 (s, 1H), 3.49-3.39 (ddd, 1H, J =
21.3, 8.9, 6.8 Hz), 2.27-2.12 (m, 2H), 1.99-1.85 (m, 1H),
1.85-1.73 (m, 1H), 1.58-1.41 (m, 2H), 1.37-1.17 (m, 2H);
13C NMR (100 MHz, CDCl3) δ = 202.4 (d, 1C, J = 18.4
Hz), 176.4, 132.9, 131.6, 129.1, 127.6, 123.9, 95.9 (d, 1C,
J = 181.2 Hz), 46.5 (d, 1C, J = 22.0 Hz), 28.2 (d, 1C, J =
3.7 Hz), 27.0 (d, 1C, J = 23.6 Hz), 20.8, 19.1 (d, 1C, J =
7.9 Hz); 19F NMR (376 MHz, CDCl3) δ –143.8 (s); HRMS
(ESI) calcd for C15H15FONa [M+Na]+: 253.0999, found:
253.0996.
3-(4-Bromophenyl)-5-fluoro-5-methylcyclopent-2-en-1-
one (2q): Yield: 81% (65 mg), colorless solid, mp 102-
1
103 °C; H NMR (400 MHz, CDCl3) δ = 7.62 (d, 2H, J =
8a-Fluoro-3-phenyl-4,5,6,7,8,8a-hexahydroazulen-
8.6 Hz), 7.51 (d, 2H, J = 8.6 Hz), 6.57 (d, 1H, J = 1.3 Hz),
1(3aH)-one (2w): Yield: 68% (50 mg), pale-yellow oil; 1H
3.42-3.21 (ddd, 1H, J = 19.8, 18.0, 1.7 Hz), 3.16-3.09 (ddd, NMR (600 MHz, CDCl3) δ = 7.60-7.42 (m, 5H), 6.44 (s,
1H, J = 18.0, 10.6, 1.7 Hz), 1.60 (d, 3H, J = 22.8 Hz); 13C
NMR (100 MHz, CDCl3) δ= 202.7 (d, 1C, J = 19.0 Hz),
168.5, 132.4, 132.0, 128.5, 126.8, 124.1, 93.8 (d, 1C, J =
183.5 Hz), 42.2 (d, 1C, J = 25.3 Hz), 21.5 (d, 1C, J = 26.9
Hz); 19F NMR (376 MHz, CDCl3) δ = –150.0 (s); HRMS
(ESI) calcd for C12H1079BrFONa [M+Na]+: 290.9791,
found: 290.9779.
1H), 3.62-3.56 (ddd, 1H, J = 25.4, 10.4, 2.0 Hz), 2.39-2.27
(m, 1H), 2.11-2.01 (m, 1H), 1.85-1.60 (m, 5H), 1.55-1.45
(m, 1H), 1.41-1.34 (m, 2H); 13C NMR (150 MHz, CDCl3)
δ = 202.8 (d, 1C, J = 17.5 Hz), 177.2, 133.4, 131.3, 129.0,
127.5, 125.7, 98.9 (d, 1C, J = 178.9 Hz), 53.0 (d, 1C, J =
25.0 Hz), 31.7 (d, 1C, J = 24.8 Hz), 30.8, 29.8, 27.9, 22.6
(d, 1C, J = 5.2 Hz); 19F NMR (565 MHz, CDCl3) δ = –
142.6 (s); HRMS (ESI) calcd for C16H17FONa [M+Na]+:
267.1156, found: 267.1153.
5-Fluoro-5-methyl-3-(naphthalen-1-yl)cyclopent-2-en-
1-one (2r): Yield: 85% (61 mg), pale-yellow oil; 1H NMR
(400 MHz, CDCl3) δ = 8.12-8.10 (m, 1H), 7.99-7.94 (m,
2H), 7.67-7.50 (m, 4H), 6.57 (d, 1H, J = 1.4 Hz), 3.65-3.47
(ddd, 1H, J = 19.8, 18.0, 1.8 Hz), 3.23 (ddd, 1H, J = 18.4,
10.5, 1.8 Hz), 1.72 (d, 3H , J = 22.8 Hz); 13C NMR (100
MHz, CDCl3) δ = 202.8 (d, 1C, J = 18.3 Hz), 171.1 (d, 1C,
J = 3.4 Hz), 133.9, 133.0, 131.1, 130.0, 129.8, 129.0, 127.4,
126.5, 125.0, 125.0, 124.5, 93.6 (d, 1C, J = 183.4 Hz), 45.9
(d, 1C, J = 24.6 Hz), 21.5 (d, 1C, J = 26.8 Hz); 19F NMR
(376 MHz, CDCl3) δ = –151.3 (s); HRMS (ESI) calcd for
C16H13FONa [M+Na]+: 263.0843, found: 263.0848.
3-Ethyl-5-fluoro-5-phenylcyclopent-2-en-1-one
(2x):
Yield: 71% (44 mg), yellow oil; 1H NMR (400 MHz,
CDCl3) δ = 7.43-7.28 (m, 5H), 6.08 (q, 1H, J = 1.6 Hz),
3.29-3.06 (m, 2H), 2.55 (q, 2H, J = 7.3 Hz), 1.28 (t, 3H, J
= 7.4 Hz); 13C NMR (100 MHz, CDCl3) δ = 201.7 (d, 1C,
J = 20.0 Hz), 181.8 (d, 1C, J = 3.6 Hz), 137.8 (d, 1C, J =
24.2 Hz), 128.6, 128.4, 125.9, 124.1 (d, 1C, J = 8.6 Hz),
96.0 (d, 1C, J = 188.5 Hz), 46.5 (d, 1C, J = 24.4 Hz), 27.0,
11.0; 19F NMR (376 MHz, CDCl3) δ = –157.2 (s); HRMS
(ESI) calcd for C13H13FONa [M+Na]+: 227.0846, found:
227.0851.
5-Fluoro-5-methyl-3-(naphthalen-2-yl)cyclopent-2-en-
1-one (2s): Yield: 88% (63 mg), yellow solid, mp 137-
5-Cyclohexyl-3-ethyl-5-fluorocyclopent-2-en-1-one (2y):
1
1
139 °C; H NMR (600 MHz, CDCl3) δ = 8.09 (s, 1H),
Yield: 64% (40 mg), colorless oil; H NMR (400 MHz,
7.95-7.86 (m, 3H), 7.75 (dd, 1H, J = 8.6, 1.8 Hz), 7.61-
7.56 (m, 2H), 6.70 (d, 1H, J = 1.3 Hz), 3.52-3.45 (ddd, 1H,
J = 24.0, 18.0, 6.0 Hz), 3.31 (ddd, 1H, J = 17.8, 10.5, 1.7
Hz), 1.65 (d, J = 22.8 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ = 202.9 (d, 1C, J = 18.3 Hz), 169.6, 134.9, 132.9,
CDCl3) δ = 5.97-5.96 (m, 1H), 2.78 (dd, 1H, J = 18.7, 11.5
Hz), 2.70 -2.56 (m, 1H), 2.43 (q, 2H, J = 7.3 Hz), 2.05-
1.86 (m, 2H), 1.85-1.75 (m, 1H), 1.69 (d, 2H, J = 12.1 Hz),
1.46-1.37 (m, 1H), 1.33-0.99 (m, 7H), 0.87-0.77 (ddd, 1H,
J = 24.8, 12.4, 3.4 Hz); 13C NMR (100 MHz, CDCl3) δ =
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800701
Advanced Synthesis & Catalysis
204.4 (d, 1C, J = 18.4 Hz), 181.9 (d, 1C, J = 3.2 Hz), 126.8
(d, 1C, J = 1.1 Hz), 98.2 (d, 1C, J = 184.3 Hz), 41.7 (d, 1C,
J = 23.1 Hz), 40.1 (d, 1C, J = 25.1 Hz), 26.9, 26.4 (d, 1C, J
= 8.7 Hz), 26.3, 26.0 (d, 1C, J = 3.9 Hz), 25.7, 25.6, 11.0;
19F NMR (376 MHz, CDCl3) δ = –158.1 (s); HRMS (ESI)
calcd for C13H19FONa [M+Na]+: 233.1312, found:
233.1303.
Chem. 2009, 7, 1716. c) T. Furuya, C. A. Kuttruff, T.
Ritter, Curr. Opin. Drug.Discovery Dev. 2008, 11, 803.
d) E. Belanger, K. Cantin, O. Messe, M. Tremblay, J.-F.
Paquin, J. Am. Chem. Soc. 2007, 129, 1034. e) R. D.
Chambers, Fluorine in Organic Chemistry; Blackwell,
2004.
5-Fluoro-3-pentyl-5-phenylcyclopent-2-en-1-one (2z):
[4] a) S. D. Putnam, M. Castanheira, G. J. Moet, D. J.
Farrell, R. N. Jones, Diagn. Microbiol. Infect. Dis. 2010,
66, 393. b) P. Hewawasam, V. K. Gribkoff, Y. Pendri,
S. I. Dworetzky, N. A. Meanwell, E. Martinez, C. G.
Boissard, D. J. Post-Munson, J. T. Trojnacki, K.
Yeleswaram, L. M. Pajor, J. Knipe, Q. Gao, R. Perrone,
J. E. Starrett Jr, Bioorg. Med. Chem. Lett. 2002, 12,
1023.
1
Yield: 61% (45 mg), pale-yellow solid, mp 48-50 °C; H
NMR (400 MHz, CDCl3) δ = 7.41-7.29 (m, 5H), 6.07 (d,
1H, J = 1.4 Hz), 3.28-3.04 (m, 2H), 2.52 (t, 2H, J = 7.6
Hz), 1.72-1.60 (m, 2H), 1.46-1.31 (m, 4H), 0.93 (t, 3H, J =
7.0 Hz); 13C NMR (100 MHz, CDCl3) δ = 201.7 (d, 1C, J =
19.9 Hz), 180.8, 137.8 (d, 1C, J = 24.2 Hz), 128.6 (d, 1C, J
= 0.7 Hz), 128.3 (d, 1C, J = 1.2 Hz), 126.6, 124.1 (d, 1C, J
= 8.6 Hz), 95.9 (d, 1C, J = 188.7 Hz), 46.5 (d, 1C, J = 24.3
Hz), 33.8, 31.4, 26.3, 22.3, 13.9; 19F NMR (376 MHz,
CDCl3) δ = –157.3(s); HRMS (ESI) calcd for C16H20FO
[M+H]+: 247.1493, found: 247.1489.
[5] For selected examples: a) R. P. Singh, J. L. Martin, J.
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Yield: 74% (59 mg), yellow solid, mp 76-78 °C; H NMR
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(400 MHz, CDCl3) δ = 7.39-7.23 (m, 10H), 6.02-6.03 (m,
1H), 3.85 (d, 1H, J = 16.1 Hz), 3.80 (d, 1H, J = 16.1 Hz),
3.22-3.05 (m, 2H); 13C NMR (100 MHz, CDCl3) δ = 201.5
(d, 1C, J = 20.0 Hz), 178.4 (d, 1C, J = 4.0 Hz), 137.6 (d,
1C, J = 24.0 Hz), 135.6, 129.1 (d, 1C, J = 3.0 Hz), 128.6 (d,
1C, J = 1.0 Hz), 128.4 (d, 1C, J = 1.0 Hz), 127.7 (d, 1C, J
= 1.0 Hz), 127.5, 124.1 (d, 1C, J = 9.0 Hz), 96.1 (d, 1C, J
= 188.0 Hz), 45.9 (d, 1C, J = 25.0 Hz), 40.4; 19F NMR
(376 MHz, CDCl3) δ = –156.7(s) . HRMS (ESI) calcd for
C18H15FONa [M+Na]+: 289.0999, found: 289.0987..
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Acknowledgements
This work was supported by National Natural Science
Foundation of China (Grants 21502093 and 21302096), Natural
Science Foundation of Jiangsu Province (GrantsBK20150871,
BK20171449 and BK20140969), the Project Fund from the
Priority Academic Program Development of Jiangsu Higher
Education Institutions (PAPD) and Top-Notch Academic
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FULL PAPER
Gold(I)-Catalyzed Tandem Cycloisomerization and
Fluorination of 1,3(4)-Enyne Esters with NFSI:
One-Pot Assembly of 5-Fluoro- Cyclopentenones
Adv. Synth. Catal. Year, Volume, Page – Page
Xianxiao Chen, Yuanyuan Zhou, Mei Hong, Yuan
Ling, Dongliang Yin, Shifa Wang, Xiaoxiang
Zhang,* and Weidong Rao*
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