Copper-Catalyzed Decarboxylative Difluoroalkylation and Perfluoroalkylation of α,β-Unsaturated Carboxylic Acids

Article abstract of DOI:10.1021/acs.joc.6b02613

Copper-catalyzed decarboxylative difluoroalkylation and perfluoroalkylation of α,β-unsaturated carboxylic acids is described. Promoted by dialkyl phosphite, this novel reaction affords fluoroalkylated motifs with excellent stereoselectivity and broad substrate scope under mild reaction conditions from readily available fluoroalkyl iodides and bromides. Preliminary mechanism study suggests that radical pathway was involved in the catalytic cycle and dialkyl phosphite had played an indispensable role in this reaction.

Full text of DOI:10.1021/acs.joc.6b02613

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Article
Copper-Catalyzed Decarboxylative Difluoroalkylation and
Perfluoroalkylation of alpha,beta-Unsaturated Carboxylic Acids
Yin-Long Lai, Dian-Zhao Lin, and Jing-Mei Huang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02613 • Publication Date (Web): 02 Dec 2016
Downloaded from http://pubs.acs.org on December 2, 2016
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Copper-Catalyzed Decarboxylative Difluoroalkylation
and Perfluoroalkylation of α,β-Unsaturated Carboxylic
Acids
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YinꢀLong Lai, DianꢀZhao Lin, and JingꢀMei Huang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou,
Guangdong 510640, China
ABSTRACT: Copperꢀcatalyzed decarboxylative difluoroalkylation and perfluoroalkylation of
α,βꢀunsaturated carboxylic acids is described. Promoted by dialkyl phosphite, this novel reaction
affords fluoroalkylated motifs with excellent stereoselectivity and broad substrate scope under
mild reaction conditions from readily available fluoroalkyl iodides and bromides. Preliminary
mechanism study suggests that radical pathway was involved in the catalytic cycle and dialkyl
phosphite had played an indispensible role in this reaction.
Introduction
The incorporation of fluorine into organic molecules has long been an important strategy in
medicinal chemistry.1 Along with the intensive studies and advances reported on the
fluoroalkylation of aromatic compounds,2 the construction of CvinylꢀCRf bonds has also been
achieved in recent decades.3 Decarboxylative coupling reactions catalyzed by transition metals
have attracted significant attention in synthetic organic chemistry and have emerged as valuable
tools for the construction of carbon−carbon bonds.4 It is envisioned that decarboxylative coupling
reactions of vinyl carboxylic acids may ensure high efficient and stereoselective synthesis of
alkenes bearing fluoroalkylated groups, and methods for decarboxylative fluoroalkylation of vinyl
carboxylic acids have gained considerable attention recently.5ꢀ8 By using Togniꢀtype electrophilic
fluoroalkylating agent 5a,e or Langlois reagent 5bꢀd, approaches to the synthesis of CvinylꢀCRf bonds
through decarboxylative crossꢀcoupling reactions have been developed by several groups (Scheme
1a). Recently, Wang’s group developed an elegant nickelꢀcatalyzed decarboxylative
difluoromethylation of vinyl carboxylic acids using ethyl iododifluoroacetate in the presence of a
base (Scheme 1b).6 More recently, Wang and coꢀworkers reported a method for decarboxylative
difluoroacetamidation of vinyl carboxylic acids with stoichiometric amounts of CuSO4 as metal
mediator at the high temperatures (Scheme 1c).7 During the preparation of this manuscript, a
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photocatalyzed decarboxylative difluoroalkylation of α,βꢀunsaturated carboxylic acids was
reported by Liu’s group (Scheme 1d).8 Although these works represent very promising advances,
general method with full scope for the difluorinated and perfluoroalkylated alkenes through
decarboxylative cross coupling using relatively lowꢀcost and commonly available fluoroalkylating
reagents, in particular fluoroalkyl bromides, are still highly desired. As one part of our continuous
efforts to develop copper catalyzed fluoroalkylations,9 we report here copper–catalyzed
decarboxylative difluoroalkylation and perfluoroalkylation of α,βꢀunsaturated carboxylic acids
with fluoroalkyl iodides and bromides in good to excellent yields with a wide substrate scope,
excellent functionalꢀgroup tolerance and excellent E selectivity under mild reaction condition
(Scheme 1e).
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Scheme 1. Synthesis of Fluoroalkylated Alkenes from Vinyl Carboxylic Acids
R2
R2
Togniꢀtype agent
or Langlois reagent
CF2R3
(a)
COOH +
R1
R1
a) Hu's work, Cu(II) (0.2 eq), 80 oC, R3=F, SO2Ph; b) Yi's work, metalꢀfree, 120 oC, R3= F;
c) Liu's work, Cu(II) (0.1 eq) or Fe(II) (0.1eq), TBHP, 50 oC, R3= F, H; d) Maiti's work Fe(III)
(1.0 eq), K2S2O8, 50 oC, R3= F; e) Duan's work, Cu(I) (0.2 eq), Ag2CO3, TBHP, 70 oC, R3= F
Wang 's work
R2
R2
Ni(II) (0.1 eq),
dppe (0.2 eq)
KOAc (1.5 eq), 70 oC
COOH
CF2COOEt
CF2CONR2
+
+
(b)
ICF2COOEt
R1
Wang 's work
R1
Cu(II) (1.2 eq)
COOH
c
( )
(d)
(e)
TMSꢀCF2CONR2
140 o
C
R
R
Liu 's work
Ru(II) (0.02 eq), Cu(I) (0.1 eq)
Et3N (1.5 eq)
CF2COOEt
CF2ꢀR2
COOH
COOH
+
+
ICF2COOEt
R
Blue LEDs, rt
R
(CuOTf)2—toluene (0.05 eq)
bipy (0.2 eq)
This work
XꢀCF2ꢀR2
X = Br, I
R1
R1
HPO(OMe)2 (2.0 eq), 60 oC
R1= aryl, heterocycle
R2 = COOEt, Rf
Results and Discussion
To start the investigation, we chose (E)ꢀcinnamic acid 1a (0.4 mmol) as the substrate and ethyl
iododifluoroacetate 2a (0.2 mmol) as the fluoroalkyl coupling partner. By using Cu2O (5 mol%) as
a catalyst and 2,2' ꢀ bipyridine (20 mol%) as the ligand the desired difluoromethylated product 3a
was obtained in a yield of 83% in the presence of HPO(OMe)2 (0.4 mmol) in DMF for 48 h (Table
1, entry 1). Surprisingly, no (E)ꢀdimethyl styrylphosphonate was detected. Encouraged by this
result, a number of other copper catalysts were investigated (Table 1, entries 2−6). The results
demonstrated that copper(I) was more efficient than copper(II) as a catalyst (Table 1, entry 4 vs. 6),
and (CuOTf)2·toluene gave the best yield and excellent E selectivity (E/Z >99:1) for this reaction
(Table 1, entry 4). Next, a series of other reductive additives,10 namely HPO(OEt)2, HPO(OtBu)2,
Et3SiH, B2pin2 and Na2S2O4 were screened (Table 1, entries 7–11). HPO(OMe)2 was found to be
the most efficient additive in this system. Meanwhile, ligands were screened and it was found that
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2,2'ꢀ bipyridine was the optimal choice (Table 1, entries 4, 12ꢀ14). Solvents were also investigated,
and DMF was found to be the most suitable solvent for this reaction (Table 1, entries 4, 15ꢀ17).
For the results of changing the substrates ratio, see Si table S3. The reaction also proceeded under
air to afford the product in a 61% yield (Table 1, entry 18).
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Table 1. Optimization of Reaction Conditionsa
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Entry
Catalyst
Ligand
Additive
Solvent
Yieldb (%), (E/Z)
1
Cu2O
bipy
HPO(OMe)2
DMF
83, (=98:2)
2c
3d
4
CuI
bipy
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OEt)2
HPO(OtBu)2
Et3SiH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
DMSO
dioxane
DMF
81, (>99:1)
85, (=95:5)
92, (>99:1)
66, (>99:1)
73, (=98:2)
84, (>99:1)
55, (>99:1)
25, (=94:6)
30, (=96:4)
15, (=91:9)
82, (>99:1)
63, (>99:1)
78, (>99:1)
82, (>99:1)
45, (>99:1)
74, (>99:1)
61, (>97:3)
CuSCN
bipy
.
(CuOTf)2 toluene
[Cu(MeCN)4]PF6
Cu(OTf)2
bipy
5e
6
bipy
bipy
.
7
(CuOTf)2 toluene
bipy
.
8
(CuOTf)2 toluene
bipy
.
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(CuOTf)2 toluene
bipy
.
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18f
(CuOTf)2 toluene
bipy
B2pin2
.
(CuOTf)2 toluene
bipy
Na2S2O4
.
(CuOTf)2 toluene
mebipy
dtbbipy
1,10-phen
bipy
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
HPO(OMe)2
.
(CuOTf)2 toluene
.
(CuOTf)2 toluene
.
(CuOTf)2 toluene
.
(CuOTf)2 toluene
bipy
.
(CuOTf)2 toluene
bipy
.
(CuOTf)2 toluene
bipy
aReaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), Cu catalyst (5 mol%), ligand (20 mol%), additive (0.4
mmol), solvent (0.6 mL), 60 °C, 48 h, under N2. bThe yield of the product was determined by 1H NMR
spectroscopy, E/Z ratios were calculated on the basis of 19F NMR spectroscopy. cCuI (10 mol%). dCuSCN (10
mol%). e[Cu(MeCN)4]PF6 (10 mol%). fUnder air. bipy=2,2'ꢀbipyridyl, mebipy=4,4'ꢀdimethylꢀ2,2'ꢀdipyridyl,
dtbbipy=4,4′ꢀdiꢀtertꢀbutylꢀ2,2′ꢀdipyridyl, 1,10ꢀphen = 1,10ꢀphenanthroline.
With the optimized reaction conditions in hand (Table 1, entry 4), a series of α,βꢀunsaturated
carboxylic acids were further evaluated. As presented in Table 2, the reaction proceeded smoothly
with various cinnamic acids to afford good to excellent yields of the corresponding
difluoroalkylated products (3a-u). Noteworthily, paraꢀ, metaꢀ, or orthoꢀsubstituted cinnamic acids,
bearing either an electronꢀdonating group (Me and OMe, 3b-c, 3k-l and 3o-p) or an
electronꢀwithdrawing (Cl and Br, 3d-e) group on the aryl ring, gave high yields of the desired
products. For the strong electronꢀwithdrawing groups (NO2, CF3, COOH, CHO, and OAc, 3f-j,
3m-n and 3q), good yields were also obtained in the presence of CF3COOH.17 Moreover,
cinnamic acid with a naphthyl group (3r) also participated in this reaction with high reactivity to
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afford the desired product in 82% of yield. Heteroareneꢀbased acrylic acids were also good
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substrates for this process and afforded the desired products in moderate to good yields (3s-u).
Intriguingly, excellent
E selectivity (E/Z>99:1) were observed in all cases. When
bromodifluoroacetate (BrCF2COOEt), a much cheaper fluoroalkyl coupling partner, was
employed, the reactions could also proceed smoothly to afford the corresponding fluoroalkylated
products in moderate to good yields (3a-f and 3s-u).
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Table 2. Copper-Catalyzed Decarboxylative Difluoroalkylation of α,βꢀUnsaturated Carboxylic Acids a, b
aReaction conditions: 1 (0.4 mmol), 2 (0.2 mmol), (CuOTf)2·toluene (5 mol%), bipy (20 mol%), HPO(OMe)2 (0.4
mmol), DMF (0.6 mL), 60 °C, 48 h, under N2. b Yield; the E/Z ratios were determined by 19F NMR spectroscopy of the
crude product mixture. cMebipy was used as ligand, CF3COOH (0.1 mmol) was added. dtbbipy
=4,4'ꢀdimethylꢀ2,2'ꢀdipyridyl.
To further examine the scope of this reaction, perfluoroalkyl halides were also used to react
with various cinnamic acids. Gratefully, the reaction proceeded smoothly with high yield by
changing the substrates ratio, solvent and the phosphite loading (see the Supporting Information
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Table S4). As shown in Table 3, a series of electronꢀrich and electronꢀdeficient cinnamic acids
were good reaction partners with perfluoroalkyl iodide, and the corresponding products (5a-n)
were obtained in moderate to good yields. Similarly, perfluoroalkyl bromides also underwent this
transformation to produce good yields (5a-f, i and l-n). Moreover, excellent E selectivity
(E/Z>99:1) were observed in all cases.
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Table 3. Copper-Catalyzed Decarboxylative Perfluoroalkylation of α,β-Unsaturated Carboxylic Acidsa, b
aReaction conditions: 1 (0.2 mmol), 4 (0.45 mmol), (CuOTf)2·toluene (10 mol%), bipy (20 mol%), HPO(OMe)2 (0.6
b
mmol), CH3CN (0.6 mL), 80 °C, 72 h, under N2. Yield; the E/Z ratios were determined by 19F NMR spectroscopy of
the crude product mixture.
In addition, a satisfactory result (76% yield) was obtained when the reaction was performed on
a gramꢀscale. Intriguingly, when bromodifluoroacetate was employed, the reaction also proceeded
smoothly to afford the corresponding fluoroalkylated product in a 70% yield (Scheme 2).
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Scheme 2. Gram-Scale Experiment
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In order to gain some insights into the reaction mechanism, a series of control experiments were
examined. When radical scavenger TEMPO (3.0 equiv) was added under the standard conditions,
the reaction was completely quenched and TEMPOꢀCF2COOEt 7 was obtained in 76% of yield
(Scheme 3, eq 1). It implied that this reaction might have proceeded through a radical pathway
which involved ꢁCF2COEt. To further verify this transformation,
a radical clock,
etheneꢀ1,1ꢀdiyldibenzene, was used to trap the difluoromethyl radical. As we expected, ꢁCF2COEt
was successfully captured and the desired product 10 was obtained in 81% (Scheme 3, eq 3).
Scheme 3. Studies on a Radical Pathway
To determine the key intermediates of the reaction, the standard reaction in the absence of
iododifluoroacetate 2a was carried out and most of the 1a was recovered with trace of (E)ꢀmethyl
cinnamic acetate 13 detected (scheme 4, eq 4). No trace of (E)ꢀdimethyl styrylphosphonate 11 was
observed. Then compound 11 was prepared according to the literature and was subjected to the
standard reaction, no desired product 3a was obtained (Scheme 4, eq 5). These results suggested
that (E)ꢀdimethyl styrylphosphonate 11 was not the intermediate although it has been reported that
it was accessible in the presence of Cu catalyst and HPO(OMe)2.11 Next, styrene 12 and
(E)ꢀmethyl cinnamic acetate 13 were also examined (Scheme 4, eq 6 and 7) and it was
demonstrated that styrene or (E)ꢀmethyl cinnamic acetate 13 could not be an intermediate for this
reaction, either.
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Scheme 4. Studies on Proposed Intermediates
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Next, the effect of copper and dialkyl phosphite was studied. Under the standard conditions,
only 26% of product 3a was obtained in the absence of HPO(OMe)2 (Table 4, entry 1). And
when the above reaction was repeated in the presence of TEMPO, compound 7 was generated in
14% of yield only (Scheme 3, eq 2).The results of eq 1 and eq 2 showed that HPO(OMe)2 had
promoted the process of the production of the ꢁCF2COEt. However, when the amount of
(CuOTf)2·toluene increased to 0.5 equiv, 72% of product was collected (Table 4, entry 2). When
the above reaction was repeated with Cu(OTf)2 (1.0 equiv) or Cu powder (1.0 equiv) instead of
(CuOTf)2·toluene (0.5 equiv), only trace or 10% of 3a was afforded (Table 4, entries 3ꢀ4). But
when 2.0 equiv of HPO(OMe)2 was added into the reaction with Cu(OTf)2 (1.0 equiv), 74% of 3a
was obtained (Table 4, entry 5). No product was observed in the absence of copper even if 2.0
equiv of HPO(OMe)2 was added (Table 4, entry 6). Hence, our results showed that in our reaction
system, partial of Cu(II) had been reduced to Cu(I) which had ensured the completion of the
catalytic cycle.12,13 It is noteworthy that other reductive reagents did not work as well as
HPO(OMe)2 on this catalytic cycle (table 1, entries 9ꢀ11 and ref 10).
Table 4. Studies on the Effect of Copper and Dialkyl phosphitea
Entry
Catalyst (equiv)
(CuOTf)2·toluene (0.05)
(CuOTf)2·toluene (0.5)
Cu(OTf)2 (1.0)
Cu (1.0)
HPO(OMe)2
Yieldb (%)
1
2
3
4
5
6
_
_
_
_
+
+
26
72
trace
10
74
0
Cu(OTf)2 (1.0)
_
aReaction conditions: 1a (0.4 mmol), 2 (0.2 mmol), Cu (X equiv), bipy (20 mol%), HPO(OMe)2
(2.0 equiv), DMF (0.6 mL), 60 °C, 48 h, under N2. bThe yield of the product was determined by
1H NMR spectroscopy.
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On the basis of the above results and salient literature,4,5b,c,e,7,8,12ꢀ14 a possible reaction pathway
was proposed as presented in Scheme 5. Copper(I) species was oxidized by fluoroalkylated
reagent 2 through a singleꢀelectron transfer to afford the fluoroalkyl radical 2' and copper(II)
species.15 Subsequently, complex I reacted with the fluoroalkyl radical 2' to furnish the radical
species II. Finally, the radical species II underwent a decarboxylation to provide the desired
fluoroalkyl product 3. Here we proposed that partial of the Cu(II) in the reaction system might
have been reduced constantly by HPO(OMe)2 to Cu(I), which is very important for the generation
of fluoroalkyl radical.
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Scheme 5. Possible Mechanism.
Conclusions
In conclusion, copperꢀcatalyzed decarboxylative difluoroalkylation and perfluoroalkylation of
α,βꢀunsaturated carboxylic acids has been developed. The method offers a reliable tool to produce
fluoroalkylated motifs in good to excellent yields from commonly available fluoroalkyl iodides
and bromides. With a wide substrate scope and excellent functionalꢀgroup tolerance, the reaction
proceeds in excellent E selectivity under mild reaction conditions. Preliminary mechanism study
suggests that radical pathway was involved in the catalytic cycle and dialkyl phosphite had played
an indispensible role in this reaction. Further studies to uncover the reaction mechanism and
possible synthetic applications are underway in our laboratory.
Experimental Section
General Information. Solvents and reagents were commercially available and used as received without further
treatment. Reactions were monitored by thinꢀlayer chromatography (TLC). 1H NMR, 13C NMR and 19F NMR
1
spectra were recorded at 400,100 ,and 375 MHz, respectively. Chemical shifts of H NMR and 13C NMR spectra
were reported as in units of parts per million (ppm) downfield from SiMe4 (δ 0.0 ppm) and relative to the signal of
1
chloroformꢀd (δ 7.26 ppm for H NMR and δ 77.0 ppm for 13C NMR).19F NMR chemical shifts were determined
relative to CFCl3 at δ 0.0. Multiplicities were given as: s (singlet); br s (broad singlet); d (doublet); t (triplet); q
(quartet); m (multiplets), etc. The number of protons (n) for a given resonance was indicated by nH. (E)ꢀDimethyl
styrylphosphonate was prepared according to the previously reported procedures.16 Cinnamic acids and other
reagents were commercially available.
General procedure for copper-catalyzed decarboxylative difluoromethylation of α,β-unsaturated
carboxylic acids with ethyl iododifluoroacetate or ethyl bromodifluoroacetate: To a 25 mL of Schlenk tube
were added α,βꢀunsaturated carboxylic acids 1 (2.0 equiv, 0.4 mmol), (CuOTf)2·toluene (5 mol %, 0.01 mmol) and
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bipy (20 mol %, 0.04 mmol) under air. The mixture was evacuated and backfilled with N2 (3 times). DMF (0.6
mL), ethyl iododifluoroacetate or ethyl bromodifluoroacetate 2 (1.0 equiv, 0.2 mmol) and HPO(OMe)2 (2.0 equiv,
0.4 mmol) were added subsequently. The Schlenk tube was then sealed with a Teflon lined cap and put into a
preheated oil bath (60 ˚C). After stirring for 48 h, the reaction mixture was cooled to room temperature. The
reaction mixture was diluted with EtOAc and filtered through a pad of celite. The filtrate was concentrated under
vacuum and purified by flash column chromatography on silica gel to give product 3.
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General procedure for copper-catalyzed decarboxylative perfluoroalkylation of α,β-unsaturated
carboxylic acids with perfluoroalkyl iodides or perfluoroalkyl bromides: To a 25 mL of Schlenk tube were
added α,βꢀunsaturated carboxylic acids 1 (1.0 equiv, 0.2 mmol), (CuOTf)2·toluene (10 mol %, 0.02 mmol) and
bipy (20 mol %, 0.04 mmol) under air. The mixture was evacuated and backfilled with N2 (3 times). CH3CN (0.6
mL), perfluoroalkyl iodides or perfluoroalkyl bromides 4 (2.25 equiv, 0.45 mmol) and HPO(OMe)2 (3.0 equiv, 0.6
mmol) were added subsequently. The Schlenk tube was then sealed with a Teflon lined cap and put into a
preheated oil bath (80 ˚C). After stirring for 72 h, the reaction mixture was cooled to room temperature. The
reaction mixture was diluted with EtOAc or diethyl ether and filtered through a pad of celite. The filtrate was
concentrated under vacuum and purified by flash column chromatography on silica gel to give product 5.
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀphenylꢀ3ꢀbutenoate 3a. The product 3a was purified with silica gel
chromatography (PE/EA=30:1) as a colorless oil (38.9 mg, 86% yield, E/Z>99:1). Analytical data
for 3a was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ 7.45 (dd,
J1=4.0 Hz, J2=8.0 Hz, 2H), 7.40ꢀ7.35 (m, 3H), 7.11ꢀ7.35 (m, 1H), 6.36ꢀ6.26 (m, 1H), 4.36 (q, J
=8.0 Hz, 2H), 1.37 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.9 (t, JCꢀF=30.0 Hz),
136.9 (t, JCꢀF=10.0 Hz), 134.1, 129.6, 128.9, 127.5, 118.9 (t, JCꢀF=30.0 Hz), 112.7 (t, JCꢀF=250.0
Hz), 63.1, 14.0. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.22 (s, 2F). (Z)ꢀisomer: δ ꢀ93.98
(s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀbutenoate 3b. The product 3b was purified with
silica gel chromatography (PE/EA=30:1) as a colorless oil (46.7 mg, 91% yield, E/Z>99:1).
Analytical data for 3b was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.39 (d, J=8.0 Hz, 2H), 7.04ꢀ6.99 (m, 1H), 6.89 (d, J=8.0 Hz, 2H), 6.21ꢀ6.12 (m, 1H), 4.35 (q,
J=8.0 Hz, 2H), 3.82 (s, 3H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ164.1 (t,
JCꢀF=30.0 Hz), 160.8, 136.3 (t, JCꢀF=10.0 Hz), 128.9, 126.8, 116.4 (t, JCꢀF=20.0 Hz), 114.3, 113.0 (t,
JCꢀF=250.0 Hz), 63.1, 55.3, 13.9. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ102.57 (s, 2F).
(Z)ꢀisomer: δ ꢀ94.11 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(pꢀtolyl)ꢀ3ꢀbutenoate 3c. The product 3c was purified with silica gel
chromatography (PE/EA=30:1) as a colorless oil (43.0 mg, 89% yield, E/Z>99:1). Analytical data
for 3c was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ.7.35 (d, J=8.0
Hz, 2H), 7.18 (d, J=8.0 Hz, 2H), 7.08ꢀ7.02 (m, 1H), 6.30ꢀ6.21 (m, 1H), 4.35 (q, J=8.0 Hz, 2H),
2.37 (s, 3H), 1.37 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 164.0 (t, JCꢀF=40.0 Hz),
139.9, 136.8 (t, JCꢀF=10.0 Hz), 131.4, 129.6, 127.4, 117.8 (t, JCꢀF=20.0 Hz), 112.9 (t, JCꢀF=250.0
Hz), 63.1, 21.3, 14.0. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ102.95 (s, 2F). (Z)ꢀisomer: δ
ꢀ94.04 (s, 2F).
(E)ꢀEthylꢀ4ꢀ(4ꢀchlorophenyl)ꢀ2,2ꢀdifluoroꢀ3ꢀbutenoate 3d. The product 3d was purified with
silica gel chromatography (PE/EA=30:1) as a colorless oil (43.2 mg, 83% yield, E/Z>99:1).
Analytical data for 3d was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.39ꢀ7.32 (m, 4H), 7.06ꢀ7.00 (m, 1H), 6.33ꢀ6.23 (m, 1H), 4.35 (q, J=8.0 Hz, 2H), 1.36 (t, J=8.0
Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.72 (t, JCꢀF=35.0 Hz), 135.52 (t, JCꢀF=10.0 Hz),
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135.48, 132.58, 129.04, 128.62, 119.45 (t, JCꢀF=25.0 Hz), 112.50 (t, JCꢀF=248.0 Hz), 63.15, 13.89.
19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.27 (s, 2F). (Z)ꢀisomer: δ ꢀ95.06 (s, 2F).
(E)ꢀEthylꢀ4ꢀ(4ꢀbromophenyl)ꢀ2,2ꢀdifluoroꢀ3ꢀbutenoate 3e. The product 3e was purified with
silica gel chromatography (PE/EA=30:1) as a colorless oil (53.6 mg, 88% yield, E/Z>99:1).
Analytical data for 3e was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.50 (d, J=8.0 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 7.04ꢀ7.00 (m, 1H), 6.34ꢀ6.25 (m, 1H), 4.35 (q,
J=8.0 Hz, 2H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.7 (t, JCꢀF=30.0 Hz),
135.6 (t, JCꢀF=10.0 Hz), 133.0, 132.0, 128.9, 123.8, 119.6 (t, JCꢀF=20.0 Hz), 112.5 (t, JCꢀF=250.0
Hz), 63.2, 13.9. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.37 (s, 2F). (Z)ꢀisomer: δ ꢀ95.10
(s, 2F).
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(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(4ꢀ(trifluoromethyl)phenyl)ꢀ3ꢀbutenoate 3f. The product 3f was
purified with silica gel chromatography (PE/EA=30:1) as a colorless oil (45.9 mg, 78% yield,
E/Z>99:1). Analytical data for 3f was consistent with that previously reported.6 1H NMR (400
MHz, CDCl3): δ 7.63 (d, J=8.0 Hz, 2H), 7.55 (d, J=8.0 Hz, 2H), 7.14ꢀ7.10 (m, 1H), 6.44ꢀ6.35 (m,
1H), 4.36 (q, J=8.0 Hz, 2H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.6 (t,
JCꢀF=40.0 Hz), 137.5, 135.4 (t, JCꢀF=10.0 Hz), 131.2 (t, JCꢀF=30.0 Hz), 127.7, 125.8 (q, JCꢀF=10.0
Hz), 125.2 (m), 121.5 (t, JCꢀF=30.0 Hz), 112.3 (t, JCꢀF=250.0 Hz), 63.3, 13.9. 19F NMR (376 MHz,
CDCl3): (E)ꢀisomer: ꢀ62.85 (s, 3F), ꢀ103.70 (s, 2F). (Z)ꢀisomer: δ ꢀ62.85 (s, 3F), ꢀ95.56 (s, 2F)
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(4ꢀnitrophenyl)ꢀ3ꢀbutenoate 3g. The product 3g was purified with silica
gel chromatography (PE/EA=10:1) a yellow solid (38.5 mg, 71% yield, E/Z>99:1). Analytical data
for 3g was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ 8.26ꢀ8.22 (m,
2H), 7.62ꢀ7.59 (m, 2H), 7.18ꢀ7.12 (m, 1H), 6.51ꢀ6.42 (m, 1H), 4.37 (q, J=8.0 Hz, 2H), 1.38 (t,
J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.37 (t, JCꢀF=30.0 Hz), 148.26, 140.23,
134.54 (t, JCꢀF=10.0 Hz), 128.19, 124.14, 123.28 (t, JCꢀF=86.0 Hz), 112.08 (t, JCꢀF=248.0 Hz),
63.44, 13.93. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.90 (s, 2F). (Z)ꢀisomer: δ ꢀ96.61 (s,
2F).
(E)ꢀ4ꢀ(4ꢀethoxyꢀ3,3ꢀdifluoroꢀ4ꢀoxoꢀ1ꢀbutenꢀ1ꢀyl)benzoic acid 3h. The product 3h was purified
with silica gel chromatography (PE/EA=10:1) as a colorless oil (36.7 mg, 68% yield, E/Z>99:1).
Analytical data for 3h was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 8.11 (d, J=8.0 Hz, 2H), 7.55 (d, J=8.0 Hz, 2H), 7.16ꢀ7.12 (m, 1H), 6.48ꢀ6.38 (m, 1H), 4.37 (q,
J=8.0 Hz, 2H), 1.38 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 171.0, 163.6 (t,
JCꢀF=40.0 Hz), 139.2, 135.7 (t, JCꢀF=10.0 Hz), 130.7, 130.1, 127.5, 121.8 (t, JCꢀF=20.0 Hz), 112.3 (t,
JCꢀF=250.0 Hz), 63.3, 14.0. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.63 (s, 2F). (Z)ꢀisomer:
δ ꢀ95.42 (s, 2F).
(E)ꢀEthylꢀ4ꢀ(4ꢀacetoxyphenyl)ꢀ2,2ꢀdifluoroꢀ3ꢀbutenoate 3i. The product 3i was purified with
silica gel chromatography (PE/EA=10:1) as a yellow oil (45.5 mg, 80% yield, E/Z>99:1).
Analytical data for 3i was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.46 (d, J=8.0 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 7.08ꢀ7.04 (m, 1H), 6.30ꢀ6.21 (m, 1H), 4.35 (q,
J=8.0 Hz, 2H), 2.30(s, 3H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 169.2,
163.8 (t, JCꢀF=40.0 Hz), 151.6, 135.8 (t, JCꢀF=10.0 Hz), 131.9, 128.5, 122.1, 119.1 (t, JCꢀF=20.0 Hz),
112.6 (t, JCꢀF=250.0 Hz), 63.1, 21.1, 13.9. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.28(s,
2F). (Z)ꢀisomer: δ ꢀ94.42 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(4ꢀformylphenyl)ꢀ3ꢀbutenoate 3j. The product 3j was purified with
silica gel chromatography (PE/EA=30:1) as a colorless oil (31.0 mg, 61% yield, E/Z>99:1).
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Analytical data for 3j was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 10.00 (s, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.59 (d, J=8.0 Hz, 2H), 7.14ꢀ7.09 (m, 1H), 6.48ꢀ6.39 (m,
1H), 4.35 (q, J=8.0 Hz, 2H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 191.4,
163.5 (t, JCꢀF=30.0 Hz), 139.8, 136.9, 135.5 (t, JCꢀF=10.0 Hz), 130.2, 128.0, 122.1 (t, JCꢀF=30.0 Hz),
112.3 (t, JCꢀF=250.0 Hz), 63.3, 13.9. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.66 (s, 2F).
(Z)ꢀisomer: δ ꢀ95.64 (s, 2F).
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(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(2ꢀmethoxyphenyl)ꢀ3ꢀbutenoate 3k. The product 3k was purified with
silica gel chromatography (PE/EA=30:1) as a colorless oil (43.5 mg, 85% yield, E/Z>99:1).
Analytical data for 3k was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ7.44ꢀ7.42 (m, 1H), 7.39ꢀ7.30 (m, 2H), 6.95 (t, J=8.0 Hz, 1H ), 6.92ꢀ6.90 (m, 1H), 6.45ꢀ6.36 (m,
1H), 4.35 (q, J=8.0 Hz, 2H), 3.87(s, 3H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3):
δ 164.2 (t, JCꢀF=30.0 Hz), 157.8, 132.3 (t, JCꢀF=10.0 Hz), 130.8, 128.4, 123.1, 120.7, 119.4 (t,
JCꢀF=20.0 Hz), 113.1 (t, JCꢀF=240.0 Hz), 111.1, 63.0, 55.5, 14.0. 19F NMR (376 MHz, CDCl3):
(E)ꢀisomer: δ ꢀ102.82 (s, 2F). (Z)ꢀisomer: δ ꢀ94.33 (s, 2F).
(E)ꢀethylꢀ2,2ꢀdifluoroꢀ4ꢀ(oꢀtolyl)ꢀ3ꢀbutenoate 3l. The product 3l was purified with silica gel
chromatography (PE/EA=30:1) as a colorless oil (39.9 mg, 83% yield, E/Z>99:1). Analytical data
for 3l was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ 7.45 (d, J=8.0
Hz, 1H), 7.33 (d, J=16.0 Hz, 1H), 7.24ꢀ7.17 (m, 3H), 6.24ꢀ6.15 (m, 1H), 4.35 (q, J=4.0 Hz, 2H),
2.37 (s, 3H), 1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 164.0 (t, JCꢀF=30.0 Hz),
136.8, 134.7 (t, JCꢀF=10.0 Hz), 133.3, 130.7, 129.4, 126.3, 126.1, 120.1 (t, JCꢀF=30.0 Hz), 112.8 (t,
JCꢀF=250.0 Hz), 63.1, 19.6, 14.0. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.02 (s, 2F).
(Z)ꢀisomer: δ ꢀ93.84 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(2ꢀnitrophenyl)ꢀ3ꢀbutenoate 3m. The product 3m was purified with
silica gel chromatography (PE/EA=30:1) as a light yellow solid (34.7 mg, 64% yield, E/Z>99:1).
Analytical data for 3m was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 8.06 (d, J=8.0 Hz, 1H), 7.68ꢀ7.52 (m, 4H), 6.31ꢀ6.22 (m, 1H), 4.38 (q, J=8.0 Hz, 2H), 1.39 (t,
J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 133.6, 133.3 (t, JCꢀF=10.0 Hz), 130.4, 130.0,
129.2, 124.9, 124.0 (t, JCꢀF =20.0 Hz), 112.1 (t, JCꢀF =240.0 Hz), 63.4, 13.9. 19F NMR (376 MHz,
CDCl3): (E)ꢀisomer: δ ꢀ103.27 (s, 2F). (Z)ꢀisomer: δ ꢀ96.83 (s, 2F).
(E)ꢀEthylꢀ4ꢀ(2ꢀacetoxyphenyl)ꢀ2,2ꢀdifluoroꢀ3ꢀbutenoate 3n. The product 3n was purified with
silica gel chromatography (PE/EA=20:1) as a colorless oil (39.8 mg, 70% yield, E/Z>99:1).
Analytical data for 3n was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.59ꢀ7.56 (m, 1H), 7.42ꢀ7.38 (m, 1H), 7.30ꢀ7.28 (m, 1H),7.18ꢀ7.13 (m, 2H), 6.40ꢀ6.30 (m, 1H),
4.37 (q, J=8.0 Hz, 2H), 2.37(s, 3H), 1.39 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ
169.0, 163.7 (t, JCꢀF=40.0 Hz), 148.8, 130.7, 130.5 (t, JCꢀF=10.0 Hz), 127.5, 126.9, 126.3, 123.1,
121.3 (t, JCꢀF=20.0 Hz), 112.4, 63.2, 20.9, 13.9. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ
ꢀ103.67 (s, 2F). (Z)ꢀisomer: δ ꢀ95.50 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(3ꢀmethoxyphenyl)ꢀ3ꢀbutenoate 3o. The product 3o was purified with
silica gel chromatography (PE/EA=30:1) as a colorless oil (42.5 mg, 83% yield, E/Z>99:1).
Analytical data for 3o was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.20 (t, J=8.0 Hz, 1H), 6.96 (t, J=8.0 Hz, 2H), 6.88 (s, 1H), 6.83ꢀ6.81 (m, 1H), 6.26ꢀ6.16 (m,
1H), 4.37 (q, J=8.0 Hz, 2H) , 3.75 (s, 3H), 1.28 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3): δ 163.9 (t, JCꢀF=40.0 Hz), 159.9, 136.8 (t, JCꢀF=10.0 Hz), 135.5, 129.9, 120.1, 119.2 (t,
JCꢀF=20.0 Hz), 115.3, 112.7 (t, JCꢀF=250.0 Hz), 112.6, 63.1, 55.3, 13.9. 19F NMR (376 MHz,
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(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(mꢀtolyl)ꢀ3ꢀbutenoate 3p. The product 3p was purified with silica gel
chromatography (PE/EA=30:1) as a colorless oil (40.9 mg, 85% yield, E/Z>99:1). Analytical data
for 3p was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ 7.20ꢀ7.17 (m,
3H), 7.09ꢀ7.07 (m, 1H), 6.99ꢀ6.95 (m, 1H), 6.25ꢀ6.16 (m, 1H), 4.27 (q, J=8.0 Hz, 2H), 2.28 (s,
3H), 1.28 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 164.0 (t, JCꢀF=30.0 Hz), 138.5,
137.0 (t, JCꢀF=10.0 Hz), 134.1, 130.4, 128.7, 128.1, 124.6, 118.6 (t, JCꢀF=30.0 Hz), 112.8 (t,
JCꢀF=250.0 Hz), 63.1, 21.3, 14.0. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.12 (s, 2F).
(Z)ꢀisomer: δ ꢀ93.65 (s, 2F).
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(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(3ꢀ(trifluoromethyl)phenyl)ꢀ3ꢀbutenoate 3q. The product 3q was
purified with silica gel chromatography (PE/EA=30:1) as a colorless oil (44.7 mg, 76% yield,
E/Z>99:1). Analytical data for 3q was consistent with that previously reported.6 1H NMR (400
MHz, CDCl3): δ 7.67 (s, 1H), 7.62 (t, J=8.0 Hz, 2H), 7.51 (t, J=8.0 Hz, 1H), 7.14ꢀ7.09 (m, 1H),
6.43ꢀ6.34 (m, 1H), 4.37 (q, J=8.0 Hz, 2H), 1.38 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3): δ 163.6 (t, JCꢀF=40.0 Hz), 135.4 (t, JCꢀF=10.0 Hz), 134.9, 131.3 (t, JCꢀF=30.0 Hz), 130.6,
129.4, 126.1 (q, JCꢀF=10.0 Hz), 125.2 (t, JCꢀF=250.0 Hz), 124.1 (q, JCꢀF=10.0 Hz), 120.9 (t,
JCꢀF=30.0 Hz), 112.3 (t, JCꢀF=250.0 Hz), 63.3, 13.9. 19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ
ꢀ62.93 (s, 3F), ꢀ103.59 (s, 2F). (Z)ꢀisomer: δ ꢀ62.93 (s, 3F), ꢀ95.72 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(naphthalenꢀ2ꢀyl)ꢀ3ꢀbutenoate 3r. The product 3r was purified with
silica gel chromatography (PE/EA=30:1) as a white solid (45.3 mg, 82% yield, E/Z>99:1).
Analytical data for 3r was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3):
δ 7.74ꢀ7.72 (m, 4H), 7.52ꢀ7.49 (m, 1H),7.43ꢀ7.39 (m, 2H), 7.18ꢀ7.13 (m, 1H), 6.38ꢀ6.28 (m, 1H),
4.28 (q, J=8.0 Hz, 2H), 1.29 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 164.0 (t,
JCꢀF=30.0 Hz), 136.9 (t, JCꢀF=10.0 Hz), 133.9, 133.3, 131.6, 128.8. 128.7, 128.4, 127.8, 127.0,
126.7, 123.3, 119.1 (t, JCꢀF=30.0 Hz), 112.9 (t, JCꢀF=250.0 Hz), 63.2, 14.0. 19F NMR (376 MHz,
CDCl3): (E)ꢀisomer: δ ꢀ102.93 (s, 2F). (Z)ꢀisomer: δ ꢀ93.60 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(pyridinꢀ2ꢀyl)ꢀ3ꢀbutenoate 3s. The product 3s was purified with silica
gel chromatography (PE/EA=30:1) as a colorless oil (27.8 mg, 61% yield, E/Z>99:1). Analytical
data for 3s was consistent with that previously reported.3a 1H NMR (400 MHz, CDCl3): δ 8.54 (d,
J=4.0 Hz, 1H), 7.65ꢀ7.60 (m, 1H), 7.34(d, J=8.0 Hz, 1H), 7.70ꢀ7.60(m, 1H), 7.08ꢀ7.02 (m, 1H),
6.86ꢀ6.77 (m, 1H), 4.27 (q, J=8.0 Hz, 2H), 1.29 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz,
CDCl3): δ 163.7 (t, JCꢀF=30.0 Hz), 152.5, 150.0, 136.8, 136.0 (t, JCꢀF=10.0 Hz), 123.9, 123.7,
123.2(t, JCꢀF=20.0 Hz), 112.7 (t, JCꢀF=240.0 Hz), 63.2, 13.9. 19F NMR (376 MHz, CDCl3):
(E)ꢀisomer: δ ꢀ103.87(s, 2F). (Z)ꢀisomer: δ ꢀ94.36 (s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(furanꢀ2ꢀyl)ꢀ3ꢀbutenoate 3t. The product 3t was purified with silica gel
chromatography (PE/EA=30:1) as a colorless oil (31.2 mg, 72% yield, E/Z>99:1). Analytical data
for 3t was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ 7.43 (s, 1H),
6.86 (d, J=16.0 Hz, 1H), 6.46 (d, J=8.0 Hz, 2H), 6.27ꢀ6.17 (m, 1H), 4.34 (q, J=8.0 Hz, 2H), 1.36 (t,
J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.8 (t, JCꢀF=40.0 Hz), 150.2, 143.9, 124.2 (t,
JCꢀF=10.0 Hz), 116.7 (t, JCꢀF=30.0 Hz), 112.8, 112.6 (t, JCꢀF=250.0 Hz), 111.9, 63.1, 13.9. 19F NMR
(376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ103.38 (s, 2F). (Z)ꢀisomer: δ ꢀ95.92(s, 2F).
(E)ꢀEthylꢀ2,2ꢀdifluoroꢀ4ꢀ(thiophenꢀ2ꢀyl)ꢀ3ꢀbutenoate 3u.The product 3u was purified with silica
gel chromatography (PE/EA=30:1) as a colorless oil (36.2 mg, 78% yield, E/Z>99:1). Analytical
data for 3u was consistent with that previously reported.6 1H NMR (400 MHz, CDCl3): δ 7.31 (d,
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J=4.0 Hz, 1H), 7.21ꢀ7.15 (m, 2H), 7.03ꢀ7.02(m, 1H), 6.16ꢀ6.06 (m, 1H), 4.35(q, J=8.0 Hz, 2H),
1.36 (t, J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 162.8 (t, JCꢀF=40.0 Hz), 137.9, 128.8
(t, JCꢀF=10.0 Hz), 128.4, 126.8, 126.2, 116.6 (t, JCꢀF=20.0 Hz), 111.4 (t, JCꢀF=250.0 Hz), 62.1, 12.9.
19F NMR (376 MHz, CDCl3): (E)ꢀisomer: δ ꢀ102.92 (s, 2F). (Z)ꢀisomer: δ ꢀ96.35 (s, 2F).
(E)ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀTridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)benzene 5a. The product 5a was
purified with silica gel chromatography (Petroleum ether) as a colorless oil (65.0 mg, 77% yield,
E/Z>99:1). Analytical data for 5a was consistent with that previously reported.3j 1H NMR (400
MHz, CDCl3): δ 7.51ꢀ7.48 (m, 2H), 7.42ꢀ7.41 (m, 3H), 7.22ꢀ7.18 (m, 1H), 6.28ꢀ6.18 (m, 1H).
13C{1H}NMR (100 MHz, CDCl3): δ 139.7 (t, JCꢀF=10.0 Hz), 133.6, 130.2, 128.9, 127.6, 114.4 (t,
JCꢀF=20.0 Hz). 19F NMR (376 MHz, CDCl3): δ ꢀ80.81 (t, J=11.3 Hz, 3F), ꢀ111.07 (m, 2F), ꢀ121.56
(m, 2F), ꢀ122.84 (m, 2F), ꢀ123.20 (m, 2F), ꢀ126.12 (m, 2F).
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(E)ꢀ1ꢀMethoxyꢀ4ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀtridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)benzene 5b. The product
5b was purified with silica gel chromatography (Petroleum ether) as a colorless oil (76.0 mg, 84%
yield, E/Z>99:1). Analytical data for 5b was consistent with that previously reported.3j 1H NMR
(400 MHz, CDCl3): δ 7.42 (d, J=8.0 Hz, 2H), 7.10 (d, J=16.0 Hz, 1H), 6.92 (d, J=8.0 Hz, 2H),
6.10ꢀ6.00 (m, 1H), 3.84 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 161.2, 139.2 (t, JCꢀF=10.0
Hz), 129.2, 126.3, 114.4, 111.8 (t, JCꢀF=20.0 Hz), 55.4. 19F NMR (376 MHz, CDCl3): δ ꢀ80.81 (t,
J=11.3 Hz, 3F), ꢀ110.54 (m, 2F),ꢀ121.58 (m, 2F), ꢀ122.85 (m, 2F), ꢀ123.19 (m, 2F),ꢀ 126.14 (m,
2F).
(E)ꢀ1ꢀMethylꢀ4ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀtridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)benzene 5c. The product 5c
was purified with silica gel chromatography (Petroleum ether) as a colorless oil (70.7 mg, 81%
yield, E/Z>99:1). Analytical data for 5c was consistent with that previously reported.3j 1H NMR
(400 MHz, CDCl3): δ 7.37 (d, J=8.0 Hz, 2H), 7.25ꢀ7.11 (m, 3H), 6.19ꢀ6.09 (m, 1H), 2.37 (s, 3H).
13C{1H}NMR (100 MHz, CDCl3): δ 140.5, 139.6 (t, JCꢀF=10.0 Hz), 130.8, 129.6, 127.6, 113.2 (t,
JCꢀF=20.0 Hz), 21.3. 19F NMR (376 MHz, CDCl3): δ ꢀ80.83 (t, J=11.3 Hz, 3F), ꢀ110.83 (m, 2F),
ꢀ121.57 (m, 2F), ꢀ122.84 (m, 2F), ꢀ123.21 (m, 2F), ꢀ126.12 (m, 2F).
(E)ꢀ1ꢀMethylꢀ2ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀtridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)benzene 5d. The product 5d
was purified with silica gel chromatography (Petroleum ether) as a colorless oil (66.3 mg, 76%
yield, E/Z>99:1). Analytical data for 5d was consistent with that previously reported.3j 1H NMR
(400 MHz, CDCl3): δ 7.50ꢀ7.45 (m, 2H), 7.34ꢀ7.23 (m, 3H), 6.18ꢀ6.08 (m, 1H), 2.43 (s, 3H).
13C{1H}NMR (100 MHz, CDCl3): δ 137.8 (t, JCꢀF=10.0 Hz), 137.0, 132.8, 130.7, 129.9, 126.5,
126.3, 115.7 (t, JCꢀF=20.0 Hz), 19.5. 19F NMR (376 MHz, CDCl3): δ ꢀ80.83 (t, J=11.3 Hz, 3F),
ꢀ110.99 (m, 2F), ꢀ121.51 (m, 2F), ꢀ122.85 (m, 2F), ꢀ123.26 (m, 2F), ꢀ126.13 (m, 2F).
(E)ꢀ1ꢀChloroꢀ4ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀtridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)benzene 5e. The product 5e
was purified with silica gel chromatography (Petroleum ether) as a colorless oil (66.6 mg, 73%
yield, E/Z>99:1). Analytical data for 5e was consistent with that previously reported.3j 1H NMR
(400 MHz, CDCl3): δ 7.43ꢀ7.37(m, 4H), 7.16ꢀ7.11 (m, 1H), 6.23ꢀ6.13 (m, 1H). 13C{1H}NMR
(100 MHz, CDCl3): δ 138.5 (t, JCꢀF=10.0 Hz), 136.2, 132.0, 129.3, 128.8, 115.0 (t, JCꢀF=20.0 Hz).
19F NMR (376 MHz, CDCl3): δ ꢀ80.84 (t, J=11.3 Hz, 3F), ꢀ111.16 (m, 2F), ꢀ121.59 (m, 2F),
ꢀ122.82 (m, 2F), ꢀ123.16 (m, 2F), ꢀ126.14 (m, 2F).
(E)ꢀ1ꢀBromoꢀ4ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀtridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)benzene 5f. The product 5f
was purified with silica gel chromatography (Petroleum ether) as a White solid (75.0 mg, 75%
yield, E/Z>99:1). Analytical data for 5f was consistent with that previously reported.3j 1H NMR
(400 MHz, CDCl3): δ 7.56ꢀ7.53 (m, 2H), 7.36ꢀ7.34 (m, 2H), 7.15ꢀ7.10 (m, 1H), 6.25ꢀ6.15 (m, 1H).
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13C{1H}NMR (100 MHz, CDCl3): δ 138.6 (t, JCꢀF=10.0 Hz), 132.4, 132.2, 129.1, 124.5, 115.0 (t,
JCꢀF=20.0 Hz). 19F NMR (376 MHz, CDCl3): δ ꢀ81.16 (m, 3F), ꢀ111.54 (m, 2F), ꢀ121.90 (m, 2F),
ꢀ123.14 (m, 2F), ꢀ123.48 (m, 2F), ꢀ126.45 (m, 2F).
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(E)ꢀ1ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀTridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)ꢀ4ꢀ(trifluoromethyl)benzene 5g. The
product 5g was purified with silica gel chromatography (Petroleum ether) as a colorless oil (61.8
mg, 63% yield, E/Z>99:1). Analytical data for 5g was consistent with that previously reported.3j
1H NMR (400 MHz, CDCl3): δ 7.67 (d, J=8.0 Hz, 2H), 7.59 (d, J=8.0 Hz, 2H), 7.26ꢀ7.20 (m, 1H),
6.35ꢀ6.25 (m, 1H). 13C{1H}NMR (100 MHz, CDCl3): δ 138.3 (t, JCꢀF=10.0 Hz), 136.8, 127.9,
125.9 (q, JCꢀF=10.0 Hz), 125.1 (m), 118.6, 117.0 (t, JCꢀF=30.0 Hz). 19F NMR (376 MHz, CDCl3): δ
ꢀ62.96 (t, 3F), ꢀ80.78 (t, J=11.3 Hz, 3F), ꢀ111.54 (m, 2F), ꢀ121.54 (m, 2F), ꢀ122.80 (m, 2F),
ꢀ123.13 (m, 2F), ꢀ126.09 (m, 2F).
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(E)ꢀ2ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,8ꢀTridecafluoroꢀ1ꢀoctenꢀ1ꢀyl)naphthalene 5h. The product 5h was
purified with silica gel chromatography (Petroleum ether) as a White solid (78.0 mg, 80% yield,
E/Z>99:1). Analytical data for 5h was consistent with that previously reported.3j 1H NMR (400
MHz, CDCl3): δ 7.88ꢀ78.5 (m, 4H), 7.63ꢀ7.52 (m, 3H), 7.36ꢀ7.32 (m, 1H), 6.37ꢀ6.27 (m, 1H).
13C{1H}NMR (100 MHz, CDCl3): δ 139.8 (t, JCꢀF=10.0 Hz), 134.1, 133.3, 131.0, 129.3, 128.8,
128.5, 127.8, 127.3, 126.8, 123.1, 114.4 (t, JCꢀF=30.0 Hz). 19F NMR (376 MHz, CDCl3): δ ꢀ80.83
(t, J=11.3 Hz, 3F), ꢀ110.89 (m, 2F), ꢀ121.53 (m, 2F), ꢀ122.82 (m, 2F), ꢀ123.05 (m, 2F), ꢀ126.13 (m,
2F).
(E)ꢀ(3,3,4,4,5,5,6,6,6ꢀNonafluoroꢀ1ꢀhexenꢀ1ꢀyl)benzene 5i. The product 5i was purified with
silica gel chromatography (Petroleum ether) as a colorless oil (45.8 mg, 71% yield, E/Z>99:1).
Analytical data for 5i was consistent with that previously reported.3k 1H NMR (400 MHz, CDCl3):
δ 750ꢀ7.48 (m, 2H), 7.43ꢀ7.41 (m, 3H), 7.27ꢀ7.17 (m, 1H), 6.27ꢀ6.11 (m, 1H). 13C{1H}NMR (100
MHz, CDCl3): δ 139.8 (t, JCꢀF=10.0 Hz), 133.6, 130.2, 129.0, 127.6, 114.3 (t, JCꢀF=20.0 Hz). 19F
NMR (376 MHz, CDCl3): δ ꢀ81.14 (m, 3F), ꢀ111.35 (m, 2F), ꢀ124.14 (m, 2F), ꢀ125.74 (m, 2F).
(E)ꢀ1ꢀMethoxyꢀ4ꢀ(3,3,4,4,5,5,6,6,6ꢀnonafluoroꢀ1ꢀhexenꢀ1ꢀyl)benzene 5j. The product 5j was
purified with silica gel chromatography (Petroleum ether) as a colorless oil (56.3 mg, 80% yield,
E/Z>99:1). Analytical data for 5j was consistent with that previously reported.3k 1H NMR (400
MHz, CDCl3): δ 7.42 (d, J=8.0 Hz, 2H), 7.12ꢀ7.08 (m, 1H), 6.91 (d, J=8.0 Hz, 2H), 6.09ꢀ5.99 (m,
1H), 3.84 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 161.3, 139.2 (t, JCꢀF=10.0 Hz), 129.3, 126.3,
114.4, 111.8(t, JCꢀF=20.0 Hz). 55.4. 19F NMR (376 MHz, CDCl3): δ ꢀ81.04 (t, J=11.3 Hz, 3F),
ꢀ110.76 (m, 2F), ꢀ124.08 (m, 2F), ꢀ125.68 (m, 2F).
(E)ꢀ1ꢀBromoꢀ4ꢀ(3,3,4,4,5,5,6,6,6ꢀnonafluoroꢀ1ꢀhexenꢀ1ꢀyl)benzene 5k. The product 5k was
purified with silica gel chromatography (Petroleum ether) as a colorless oil (57.6mg, 72% yield,
E/Z>99:1). Analytical data for 5k was consistent with that previously reported.3k 1H NMR (400
MHz, CDCl3): δ 7.54 (d, J=8.0 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 7.14ꢀ7.10 (m, 1H), 6.24ꢀ6.149 (m,
1H). 13C{1H}NMR (100 MHz, CDCl3): δ 138.6 (t, JCꢀF=10.0 Hz), 132.4, 132.2, 129.1, 124.5,
115.0 (t, JCꢀF=20.0 Hz). 19F NMR (376 MHz, CDCl3): δ ꢀ80.03 (m, 3F), ꢀ111.44 (m, 2F), ꢀ124.05
(m, 2F), ꢀ125.66 (m, 2F).
(E)ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10ꢀHeptadecafluoroꢀ1ꢀdecenꢀ1ꢀyl)benzene 5l. The product
5l was purified with silica gel chromatography (Petroleum ether) as a colorless oil (84.6 mg, 81%
yield, E/Z>99:1). Analytical data for 5l was consistent with that previously reported.3l 1H NMR
(400 MHz, CDCl3): δ 7.50ꢀ7.47 (m, 2H), 7.42ꢀ7.40 (m, 3H), 7.20ꢀ7.16 (m, 1H), 6.26ꢀ6.16 (m, 1H).
13C{1H}NMR (100 MHz, CDCl3): δ 139.8 (t, JCꢀF=10.0 Hz), 133.6, 130.2, 129.0, 127.6, 114.4 (t,
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JCꢀF=20.0 Hz). 19F NMR (376 MHz, CDCl3): δ ꢀ80.83 (m, 3F), ꢀ111.10 (m, 2F), ꢀ121.38 (m, 2F),
ꢀ121.92(m, 4F), ꢀ122.73 (m, 2F), ꢀ123.21 (m, 2F), ꢀ126.15(m, 2F).
(E)ꢀ1ꢀChloroꢀ4ꢀ(3,3,4,4,5,5,6,6,6ꢀnonafluoroꢀ1ꢀhexenꢀ1ꢀyl)benzene 5m. The product 5m was
purified with silica gel chromatography (Petroleum ether) as a colorless oil (50.6 mg, 71% yield,
E/Z>99:1). Analytical data for 5m was consistent with that previously reported.3j 1H NMR (400
MHz, CDCl3): δ 7.43ꢀ7.37(m, 4H), 7.16ꢀ7.12 (m, 1H), 6.24ꢀ6.14 (m, 1H). 13C{1H}NMR (100
MHz, CDCl3): δ 138.5 (t, JCꢀF=10.0 Hz), 136.2, 132.0, 129.3, 128.9, 115.0 (t, JCꢀF=20.0 Hz). 19F
NMR (376 MHz, CDCl3): δ ꢀ81.01 (m, 3F), ꢀ111.29 (m, 2F), ꢀ124.03 (m, 2F), ꢀ125.66 (m, 2F).
(E)ꢀ1ꢀ(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10ꢀHeptadecafluoroꢀ1ꢀdecenꢀ1ꢀyl)ꢀ4ꢀmethoxybenzene
5n. The product 5n was purified with silica gel chromatography (Petroleum ether) as a colorless
oil (91.7 mg, 83% yield, E/Z>99:1). Analytical data for 5n was consistent with that previously
reported.3j 1H NMR (400 MHz, CDCl3): δ 7.42 (d, J=8.0 Hz, 2H), 7.113ꢀ7.09 (m, 1H), 6.92 (d,
J=8.0 Hz, 2H) , 6.10ꢀ6.00 (m, 1H), 3.84 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 161.2, 139.1
(t, JCꢀF=10.0 Hz), 129.2, 126.3, 114.4, 111.8 (t, JCꢀF=20.0 Hz), 55.4. 19F NMR (376 MHz, CDCl3):
δ ꢀ80.85 (m, 3F), ꢀ110.56 (m, 2F), ꢀ121.38 (m, 2F), ꢀ121.91 (m, 4F), ꢀ122.73 (m, 2F), ꢀ123.18 (m,
2F), ꢀ126.13 (m, 2F).
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Ethylꢀ2,2ꢀdifluoroꢀ2ꢀ((2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyl)oxy)acetate 7. The product 7 was
purified with silica gel chromatography (Petroleum ether) as a colorless oil (42.5 mg, 76% yield).
Analytical data for 7 was consistent with that previously reported.3g 1H NMR (400 MHz, CDCl3):
δ 4.28 (q, J=8.0 Hz, 2H) , 1.52ꢀ1.46 (m, 6H), 1.30 (t, J=4.0 Hz, 3H), 1.12ꢀ1.10 (m, 12H).
13C{1H}NMR (100 MHz, CDCl3): δ 160.7 (t, JCꢀF=60.0 Hz), 115.5 (t, JCꢀF=270.0 Hz), 63.0, 61.4,
40.1, 33.4 (t, JCꢀF=10.0 Hz), 20.7, 16.9, 13.9. 19F NMR (376 MHz, CDCl3): δ ꢀ73.45.
Ethylꢀ2,2ꢀdifluoroꢀ4,4ꢀdiphenylꢀ3ꢀbutenoate 11. The product 11 was purified with silica gel
chromatography (Petroleum ether) as a colorless oil (49.2 mg, 81% yield). Analytical data for 11
was consistent with that previously reported.3g 1H NMR (400 MHz, CDCl3): δ 7.29ꢀ7.21 (m, 6H),
7.18ꢀ7.11 (m, 2H), 7.13ꢀ7.12 (m, 2H), 6.19 (t, J=12.0 Hz, 1H), 3.83 (q, J=8.0 Hz, 2H), 1.09 (t,
J=8.0 Hz, 3H). 13C{1H}NMR (100 MHz, CDCl3): δ 163.5 (t, JCꢀF=30.0 Hz), 151.0 (t, JCꢀF=10.0
Hz), 140.5, 137.1, 129.9 (t, JCꢀF=10.0 Hz), 129.1, 128.6, 128.4, 128.0, 127.9, 119.5 (t, JCꢀF=30.0
Hz), 112.6 (t, JCꢀF=250.0 Hz), 62.8, 13.7. 19F NMR (376 MHz, CDCl3): δ ꢀ91.00.
ASSOCIATED CONTENT
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: chehjm@scut.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China (Grant Nos. 21372089 and
201672074) for financial support.
Supporting Information
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Experimental procedures and spectroscopic data. This material is available free of charge via the
Internet at http://pubs.acs.org.
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