Structure-dependent selective O- or C-trifluoroethylation of 1,3-dicarbonyls by mesityl(2,2,2-trifluoroethyl)iodonium triflate

Article abstract of DOI:10.1016/j.jfluchem.2017.09.009

Reaction of [ArICH₂CF₃][OTf] with structurally diversified 1,3-dicarbonyls and an appropriate base at room temperature gave O-trifluoroethylated products, C-trifluoroethylated products, or a mixture of O- and C-trifluoroethylated products in good yields. The product type was dramatically dependent upon the structure of the starting 1,3-dicarbonyls in this reaction. The cyclic 1,3-diketones exclusively afforded the O-trifluoroethylated products, whereas the acyclic 1,3-diketones, β-keto esters, and malonates selectively or specifically formed the C-trifluoroethylated products. Li₂CO₃ facilitated the C-trifluoroethylation of acyclic 1,3-diketones and β-keto esters. The reaction proceeded under mild conditions, without pre-activation of 1,3-dicarbonyls and use of strong base, and demonstrated a catalyst-free structure-dependent regioselective trifluoroethylation of 1,3-dicarbonyls by mesityl(2,2,2-trifluoroethyl)iodonium triflate.

Full text of DOI:10.1016/j.jfluchem.2017.09.009

Accepted Manuscript
Title: Structure-dependent selective O- or
C-trifluoroethylation of 1,3-dicarbonyls by
mesityl(2,2,2-trifluoroethyl)iodonium triflate
Authors: Cheng-Long Zhao, Jing Yang, Zhou-Zhou Han,
Cheng-Pan Zhang
PII:
S0022-1139(17)30370-6
DOI:
Reference:
http://dx.doi.org/10.1016/j.jfluchem.2017.09.009
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20-9-2017
22-9-2017
Please cite this article as: Cheng-Long Zhao, Jing Yang, Zhou-Zhou Han, Cheng-
Pan Zhang, Structure-dependent selective O- or C-trifluoroethylation of 1,3-
dicarbonyls by mesityl(2,2,2-trifluoroethyl)iodonium triflate, Journal of Fluorine
Chemistryhttp://dx.doi.org/10.1016/j.jfluchem.2017.09.009
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Structure-dependent selective O- or C-trifluoroethylation of 1,3-dicarbonyls by
mesityl(2,2,2-trifluoroethyl)iodonium triflate
Cheng-Long Zhao, Jing Yang, Zhou-Zhou Han, Cheng-Pan Zhang*
School of Chemistry, Chemical Engineering and Life Science, Wuhan University of
Technology, 205 Luoshi Road, Wuhan, 430070, China.
E-mail: zhangchengpan1982@hotmail.com; cpzhang@whut.edu.cn
Graphic abstract
Highlights
 A catalyst-free structure-dependent regioselective trifluoroethylation is
described.
 Cyclic 1,3-diketones exclusively afforded the O-trifluoroethylated products.
 Acyclic 1,3-dicarbonyls selectively formed the C-trifluoroethylated products.
 Li2CO3 facilitated the C-trifluoroethylation of acyclic 1,3-dicarbonyls.
 The reaction avoided pre-activation of 1,3-dicarbonyls and use of strong base.
Abstract
Reaction of [ArICH2CF3][OTf] with structurally diversified 1,3-dicarbonyls and an
appropriate base at room temperature gave O-trifluoroethylated products,
C-trifluoroethylated products, or a mixture of O- and C-trifluoroethylated products in
good yields. The product type was dramatically dependent upon the structure of the
starting 1,3-dicarbonyls in this reaction. The cyclic 1,3-diketones exclusively afforded
the O-trifluoroethylated products, whereas the acyclic 1,3-diketones, β-keto esters,
and malonates selectively or specifically formed the C-trifluoroethylated products.
Li2CO3 facilitated the C-trifluoroethylation of acyclic 1,3-diketones and β-keto esters.

The reaction proceeded under mild conditions, without pre-activation of
1,3-dicarbonyls and use of strong base, and demonstrated a catalyst-free
structure-dependent regioselective trifluoroethylation of 1,3-dicarbonyls by
mesityl(2,2,2-trifluoroethyl)iodonium triflate.
Keywords: (2,2,2-trifluoroethyl)iodonium; trifluoroethylation; 1,3-dicarbonyls;
structure-dependent
Introduction
Fluorine-containing functionalities have been widely used to modify the conformation,
stability, basicity, and intrinsic properties of organic molecules [1]. Fluorinated
analogues of pharmaceutically relevant compounds usually possess properties
conducive to drug development, such as improved lipophilicity, metabolic stability,
and bioavailability compared to their non-fluorinated counterparts [2a]. The
incorporation of fluorine atom(s) into the target molecules has become a general
strategy for pharmaceutical research and drug development [2]. Among various
fluorine-containing molecules, trifluoroethylated compounds are of great interest for
their applications in medicinal chemistry and materials science [2,3]. A growing
number of trifluoroethyl-containing compounds with biological activities, such as
antimalarial activity, hypolipidemic activity, anesthetic property, anti-inflammatory
activity, and enzyme inhibition ability, have been developed [4]. Because the naturally
occurring pathway is lacking, chemists have to search for reagents and
trifluoroethylation methods to prepare these molecules [5]. The direct carbon- and
heteroatom-CH2CF3 bond formation has attracted much attention [5]. The transition
metal-mediated/catalyzed or transition metal-free trifluoroethylation of organic
scaffolds, such as arylboronic acids or esters, aryl iodides, arene, alkynes, alkenes,
anilines, and aryl Grignard reagents, have been successfully established [5,6].
Reagents that were efficient for these reactions include CF3CH2I or CF3CH2OTs,
CF3CHN2 or CF3CH2NH2, CF3CHCl2, (CF3CH2SO2)2Zn, CF3CH2SO2Cl, CF3CO2H,
and aryl(2,2,2-trifluoroethyl)iodonium salts ([ArICH2CF3]X) [5-7].
Aryl(2,2,2-trifluoroethyl)iodoniums, first synthesized by Umemoto and later
modified by DesMarteau and Novák, has proved to be highly efficient electrophilic
trifluoroethylation reagents for heteroatom and carbon nucleophiles such as amines,
peptides, alcohols, phenols, thiols, sulfides, carbohydrates, thioglycosides, fatty acids,
phosphines, and electron-rich arenes [8]. These reactions proceeded smoothly under

catalyst-free conditions to form the pivotal N-CH2CF3, O-CH2CF3, S-CH2CF3,
P-CH2CF3, and C-CH2CF3 bonds for a variety of bioactive molecules, and also
demonstrated that [ArICH2CF3]X (Ar = C6H5, 2,4,6-(CH3)3C6H2; X = OTf, NTf2)
possess much more powerful trifluoroethylation ability than other CF3CH2 transfer
reagents.
Recently,
the
palladium-catalyzed
reactions
of
aryl(2,2,2-trifluoroethyl)iodonium triflates with anilides, aromatic amides, and indoles
via C-H activation or with arylboronic acids via Suzuki-Miyaura cross-coupling have
been explored [9], which represent the state-of-the-art transition metal-catalyzed
trifluoroethylation methods using [ArICH2CF3]X as the CF3CH2 source.
The preliminary reaction of carbanions with [PhICH2CF3][OTf] was notified by
Umemoto and coworkers, wherein [PhICH2CF3][OTf] reacted with the sodium salt of
diethyl methylmalonate or a silyl enol ether to afford the corresponding
C-trifluoroethylated product in a very low yield [10a]. Later, reaction of trimethylsilyl
enol ethers with [PhICH2CF3][OTf] in the presence of KF at room temperature
provided β-trifluoromethyl carbonyl derivatives in moderate to good yields [10b]. The
reaction happened specifically at the α-carbon sites of carbonyls. Recently, Shen and
coworkers
disclosed
that
3,3-dimethyl-1-(perfluoroethyl)-1,3-dihydro-1λ3-benzo[d][1,2]iodaoxole (BIX-C2F5)
reacted with β-keto esters at room temperature in the presence of DBU or K2CO3 to
give α-pentafluoroethylated β-keto esters in good yields; pentafluoroethylation
occurred at the tertiary active methine group of 1,3-dicarbonyls [11]. Interestingly, we
found in this work that the reaction of [ArICH2CF3][OTf] with 1,3-dicarbonyls gave
specifically O-trifluoroethylated or C-trifluoroethylated products, which was
dramatically dependent upon the structure of 1,3-dicarbonyls.
At the beginning, the reaction of cyclohexane-1,3-dione (1a) and
mesityl(2,2,2-trifluoroethyl)iodonium triflate (2a) was chosen as the model reaction to
optimize the reaction conditions. Treatment of 1a with 2a (1.5 equiv) in CH2Cl2 in the
presence of K2CO3 (2.0 equiv) at room temperature overnight furnished
3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3a) in 61% yield, as a sole product.
This initial result was much different from the previous reports that silyl enol ethers
reacted with [PhICH2CF3][OTf] providing only α-trifluoroethyled carbonyl
derivatives [10]. The choice of solvent had a significant influence on the reaction.
Acetonitrile appeared to be the best solvent among CH2Cl2, CH3CN, THF, DMF, and

DMSO (entries 1-5, Table 1), as the reaction performed in CH3CN yielded 75% of 3a.
Other bases such as K3PO4, Li2CO3, NaHCO3, and Cs2CO3 were also suitable agents
for the O-trifluoroethylation of 1a (entries 6-9, Table 1). Li2CO3 was found to be a
better choice, which gave 3a in 89% yield (entry 10, Table 1). Decreasing the
equivalents of Li2CO3 from 2.0 to 1.5 equiv lead to 3a in 99% yield (entry 11, Table
1). Using phenyl(2,2,2-trifluoroethyl)iodonium triflate [PhICH2CF3][OTf] (2b)
instead of 2a in the same reaction afforded 3a in a slightly lower isolated yield (entry
12, Table 1).
With the optimized reaction conditions in hand (1 / 2a (1.5 equiv) / Li2CO3 (1.5
equiv) / CH3CN / r.t. / N2 / overnight), various cyclic 1,3-diketones were examined
(Table 2). Complex cyclohexane-1,3-diones (1b-o) reacted with [MesICH2CF3][OTf]
in the presence of Li2CO3 to afford exclusively the O-trifluoroethylated products
(3b-o) in good yields. The transformation did not require any strong base that is
harmful to mesityl(2,2,2-trifluoroethyl)iodonium triflate or process that is usually
used for pre-activation of 1,3-dicarbonyls [10,11]. Substituents such as methyl, phenyl,
allyl, benzyl, cyclohexylmethyl, and cinnamyl groups at the 2- and/or 5-position of
cyclohexane-1,3-diones had a little influence on the reaction. Substrates bearing
benzyl groups at the 2-positions, with either electron-withdrawing or -donating
functionalities on the phenyl rings, gave comparable yields of the desired products. In
the case of 3e and 3g, the reaction using K2CO3 instead of Li2CO3 led to higher yields
of the products. Furthermore, reactions of cyclopentane-1,3-dione and its derivatives
(1p-r) with 2a under the standard conditions furnished the O-trifluoroethylated
products (3p-r) in good yields. Nevertheless, cycloheptane-1,3-dione (1s) reacted
with 2a in the same conditions providing 3s only in 6% isolated yield, and most of 1s
was recovered. Replacement of Li2CO3 with the stronger bases such as KOH and
LiOH in the same reaction failed to improve the yield of 3s.
The acyclic 1,3-dicarbonyl compounds were also tested in this reaction (Table 3).
Treatment of methyl 1-oxo-2,3-dihydro-1H-indene-2-carboxylate (1t) with 2a (2.0
equiv) in the presence of Li2CO3 (1.5 equiv) and 4Å MS (100 mg) for 24 h provided a
mixture of methyl 3-(2,2,2-trifluoroethoxy)-1H-indene-2-carboxylate (3t, 18%) and

methyl 1-oxo-2-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-indene-2-carboxylate (3t’,
46%). The C-trifluoroethylated compound was obtained as the major product.
Addition of 4Å MS to the reaction mixture facilitated the trifluoroethylation (see SI).
Taking Cs2CO3 instead of Li2CO3, the yield of 3t was promoted and the formation of
3t’ was somewhat inhibited. Similar phenomena were also observed when using
1,3-diphenylpropane-1,3-dione (1v) as substrate in the reaction, which formed a
mixture of (Z)-1,3-diphenyl-3-(2,2,2-trifluoroethoxy)prop-2-en-1-one (3v, 19%) [12]
and 1,3-diphenyl-2-(2,2,2-trifluoroethyl)propane-1,3-dione (3v’, 69%) in the presence
of Li2CO3, with the C-trifluoroethylated product (3v’) being predominant. These
results indicated that Li2CO3 benefited the C-trifluoroethylation, which might be
attributed to the strong interaction between the Li+ cation and the oxygen atoms of 1t
or 1v [13]. This hypothesis was further proved by the observations that reaction of 1v
and 2a with a mixture of Li2CO3/15-crown-5 or [n-Bu4N][OH]•30H2O gave a higher
percentage of O-trifluoroethylated product (3v) than that using Li2CO3 without extra
Li+ cation trap.
In
addition,
the
reaction
of
methyl
or
5,6-dimethoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate
(1u)
1-(4-methoxyphenyl)-3-phenylpropane-1,3-dione (1w) with 2a and Li2CO3 provided
the C-trifluoroethylated product (3u’ or 3w’) in 43% or 31% isolated yield (Table 3).
The corresponding O-trifluoroethylated products were likely formed in these reactions
according to the 19F NMR analysis of the reaction mixtures; however, they couldn’t be
isolated due to their formation in trace amounts. Furthermore, the reaction of
1-phenylbutane-1,3-dione (1x) or 1-phenylpentane-1,3-dione (1y) with
[MesICH2CF3][OTf]
under
the
standard
conditions
gave
1-phenyl-2-(2,2,2-trifluoroethyl)butane-1,3-dione (3x’) in 68% yield or
1-phenyl-2-(2,2,2-trifluoroethyl)pentane-1,3-dione (3y’) in 56% (or 65%) yield.
Treatment of excess diethyl malonate (1z) or dibenzyl malonate (1aa) with 2a in the
presence of KOH and 4Å MS (100 mg) supplied mono C-trifluoroethylated product
(3z’ or 3aa’) in 42% or 51% yield. Since malonates are less acidic than 1,3-diones or
β-keto esters [14], the stronger base (KOH) was necessary to accomplish the reaction.
In conclusion, we have found that reaction of [ArICH2CF3][OTf] with structurally
diversified 1,3-dicarbonyls under mild basic conditions gave O-trifluoroethylated
products, C-trifluoroethylated products, or a mixture of O- and C-trifluoroethylated

products in good yields. The product distribution was dramatically dependent upon
the structure of 1,3-dicarbonyls. The cyclic 1,3-diketones exclusively yielded the
O-trifluoroethylated products, while the acyclic 1,3-diketones, β-keto esters, and
malonates selectively or specifically constructed the C-trifluoroethylated compounds.
The use of Li2CO3 as base facilitated the C-trifluoroethylation of acyclic
1,3-diketones and β-keto esters. This mild and simple reaction demonstrated a
structure-dependent regioselective O- or C-trifluoroethylation of 1,3-dicarbonyls by
mesityl(2,2,2-trifluoroethyl)iodonium triflate without any pre-activation of the
starting materials.
Experimental
1. General considerations
All reactions were carried out under a nitrogen atmosphere. Unless otherwise
1
specified, NMR spectra were recorded in CDCl3 on a 500 or 400 MHz (for H), 471
19
13
or 376 MHz (for F), or 126 MHz (for C) spectrometer. All chemical shifts were
reported in ppm relative to TMS (0 ppm) for 1H NMR and PhCF3 (-63.5 ppm) for 19F
NMR as internal or external standard. The HPLC experiments were carried out on a
Waters e2695 instrument (column: J&K, RP-C18, 5 μm, 4.6 × 150 mm), and the
yields of product were determined by using the corresponding pure compound as the
external standard. Melting points of the products were measured and uncorrected. MS
experiments were performed on a TOF-Q ESI or CI/EI instrument. Solvents were
dried before use according to the literature.15 Trifluoroethylation reagents 2a and 2b
were synthesized according to the literature.8j 1,3-Dicarbonyls 1b-d,16a 1e-f,16b 1g,16a
1h-j,16b 1l-m,16a 1r16a, 1t,16c 1u,16c 1w,16d 1y,16d were synthesized according to the
literatures. Other reagents were all purchased from commercial sources and used
without further purification.
2. General procedures for the reaction of 1,3-dicarbonyls with
[ArICH2CF3][OTf]
Procedure A: In a nitrogen filled glovebox, a sealed tube was charged with 1,3-dione
(1, 0.4 mmol), [MesICH2CF3][OTf] (2a, 0.6 mmol), Li2CO3 (0.6 mmol), and CH3CN
(2 mL) with stirring. The mixture was reacted at room temperature overnight and
evaporated to dryness under reduced pressure. The residue was purified by column
chromatography on silica gel using petroleum ether / ethyl acetate = 2 : 1 (v / v) as

eluents to give the trifluoroethylated product (3a-s).
Procedure B: In a nitrogen filled glovebox, a sealed tube was charged with 1,3-dione
(1, 0.2 mmol), [MesICH2CF3][OTf] (2a, 0.4 mmol), Li2CO3 or Cs2CO3 (0.3 mmol), 4
Å MS (100 mg), and CH3CN (2 mL) with stirring. The mixture was reacted at room
temperature for 24 h and evaporated to dryness under reduced pressure. The residue
was purified by column chromatography on silica gel using petroleum ether / ethyl
acetate = 10 : 1 (v / v) as eluents to give the trifluoroethylated product (3t, 3v, and
3t’-3y’).
Procedure C: In a nitrogen filled glovebox, a sealed tube was charged with malonate
(1, 1.5 mmol), [MesICH2CF3][OTf] (2a, 0.5 mmol), KOH (0.55 mmol), 4 Å MS (100
mg), and CH3CN (2 mL) with stirring. The mixture was reacted at room temperature
for 24 h and evaporated to dryness under reduced pressure. The residue was purified
by column chromatography on silica gel using a mixture of petroleum ether and ethyl
acetate as eluents to give the trifluoroethylated product (3z’ and 3aa’).
3-(2,2,2-Trifluoroethoxy)cyclohex-2-en-1-one (3a):
White solid, 64.5 mg, 83% yield. M.p.: 61-63 °C. 1H NMR (400 MHz, CDCl3) δ 5.31
(s, 1H), 4.17 (q, J = 8.0 Hz, 2H), 2.49 (t, J = 6.4 Hz, 2H), 2.36 (t, J = 6.4 Hz, 2H),
2.01 (m, 2H). 19F NMR (376 MHz, CDCl3) δ -73.6 (t, J = 7.9 Hz, 3F). 13C NMR (126
MHz, CDCl3) δ 199.1, 175.8, 122.7 (q, J = 277.2 Hz), 103.8, 65.0 (q, J = 36.5 Hz),
36.8, 28.5, 21.1. IR (KBr): 3065, 2967, 2925, 2906, 2840, 1679, 1656, 1615, 1455,
1434, 1384, 1355, 1330, 1303, 1283, 1247, 1220, 1187, 1141, 1068, 1039, 968, 912,
868, 853, 834, 762, 692, 635 cm-1. HRMS-EI (m/z) calcd. for C8H9F3O2 ([M]+):
194.0555; Found: 194.0553.
2-Benzyl-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3b):
Light yellow solid, 76.2 mg, 67% yield. M.p.: 62-64 °C. 1H NMR (500 MHz, CDCl3)
δ 7.28-7.22 (m, 4H), 7.15 (t, J = 7.0 Hz, 1H), 4.35 (q, J = 8.0 Hz, 2H), 3.67 (s, 2H),
19
2.54 (t, J = 6.1 Hz, 2H), 2.41 (t, J = 6.6 Hz, 2H), 2.04 (m, 2H). F NMR (471 MHz,
CDCl3) δ -78.1 (t, J = 8.0 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 197.9, 168.5, 141.0,
128.9, 128.2, 125.7, 123.0 (q, J = 278.5 Hz), 121.8, 64.4 (q, J = 36.5 Hz), 36.4, 28.0,
25.2, 20.7. IR (KBr): 3083, 3059, 3029, 3005, 2952, 2925, 2893, 2868, 2845, 2819,
1648, 1622, 1494, 1454, 1426, 1377, 1362, 1337, 1287, 1232, 1175, 1160, 1108, 1093,
1052, 1030, 983, 967, 921, 877, 853, 759, 714, 702, 691, 671, 608 cm-1. HRMS-EI

(m/z) calcd. for C15H15F3O2 ([M]+): 284.1024; Found: 284.1012.
2-(4-Chlorobenzyl)-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3c):
White solid, 86.7 mg, 68% yield. M.p.: 56-58 °C. 1H NMR (500 MHz, CDCl3) δ 7.16
(s, 4H), 4.34 (q, J = 7.8 Hz, 2H), 3.59 (s, 2H), 2.53 (t, J = 6.3 Hz, 2H), 2.38 (t, J = 6.0
19
13
Hz, 2H), 2.02 (m, 2H). F NMR (376 MHz, CDCl3) δ -74.1 (t, J = 7.8 Hz, 3F). C
NMR (126 MHz, CDCl3) δ 197.9, 168.5, 141.0, 128.9, 128.2, 125.7, 123.0 (q, J =
278.5 Hz), 121.8, 64.4 (q, J = 36.5 Hz), 36.4, 27.9, 25.1, 20.7. IR (KBr): 3042, 3028,
2985, 2964, 2941, 2909, 2876, 2850, 1636, 1621, 1490, 1455, 1423, 1370, 1337, 1302,
1291, 1257, 1226, 1208, 1159, 1111, 1088, 1053, 1016, 974, 925, 877, 857, 841, 814,
801, 735, 703, 689, 663, 641 cm-1. HRMS-EI (m/z) calcd. for C15H14ClF3O2 ([M]+):
318.0634; Found: 318.0640.
2-(2-Methylbenzyl)-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3d):
Light yellow solid, 100.2 mg, 84% yield. M.p.: 38-40 °C. 1H NMR (400 MHz, CDCl3)
δ 7.09 (m, 1H), 7.06-7.02 (m, 2H), 6.97 (m, 1H), 4.27 (q, J = 8.0 Hz, 2H), 3.61 (s,
2H), 2.56 (t, J = 6.2 Hz, 2H), 2.43 (t, J = 6.7 Hz, 2H), 2.35 (s, 3H), 2.07 (m, 2H). 19F
NMR (376 MHz, CDCl3) δ -74.2 (t, J = 8.0 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ
198.0, 169.1, 138.6, 136.3, 129.9, 127.9, 125.7, 125.7, 122.9 (q, J = 278.5 Hz), 121.3,
64.4 (q, J = 36.5 Hz), 36.5, 25.4, 25.1, 20.8, 19.8. IR (KBr): 3101, 3060, 3049, 3018,
2953, 2931, 2895, 2873, 1649, 1631, 1619, 1490, 1456, 1422, 1373, 1316, 1286, 1219,
1168, 1117, 1095, 1087, 1050, 986, 960, 919, 858, 831, 783, 744, 670 cm-1. HRMS-EI
(m/z) calcd. for C16H17F3O2 ([M]+): 298.1181; Found: 298.1184.
2-(4-Nitrobenzyl)-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3e):
1
Light yellow solid, 90.9 mg, 69% yield (K2CO3 as the base). M.p.: 83-85 °C. H
NMR (500 MHz, CDCl3) δ 8.07 (d, J = 8.5 Hz, 2H), 7.39 (d, J = 8.5 Hz, 2H), 4.40 (q,
J = 8.0 Hz, 2H), 3.73 (s, 2H), 2.59 (t, J = 6.0 Hz, 2H), 2.43 (t, J = 6.5 Hz, 2H), 2.07
(m, 2H). 19F NMR (471 MHz, CDCl3) δ -74.2 (t, J = 8.0 Hz, 3F). 13C NMR (126 MHz,
CDCl3) δ 197.6, 169.3, 148.9, 146.3, 129.7, 123.5, 122.9 (q, J = 278.5 Hz), 120.3,
64.5 (q, J = 36.5 Hz), 36.2, 28.1, 25.2, 20.7. IR (KBr): 3108, 2933, 2851, 1658, 1630,
1598, 1515, 1458, 1430, 1370, 1340, 1294, 1231, 1171, 1159, 1107, 1056, 1012, 969,
922, 884, 856, 806, 732, 702, 632 cm-1. HRMS-EI (m/z) calcd. for C15H14F3NO4
([M]+): 329.0875; Found: 329.0880.

4-((6-Oxo-2-(2,2,2-trifluoroethoxy)cyclohex-1-en-1-yl)methyl)benzonitrile (3f):
1
White solid, 96.5 mg, 78% yield. M.p.: 130-132 °C. H NMR (500 MHz, CDCl3) δ
7.50 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 4.38 (q, J = 8.0 Hz, 2H), 3.68 (s,
19
2H), 2.57 (t, J = 6.0 Hz, 2H), 2.41 (t, J = 6.5 Hz, 2H), 2.06 (m, 2H). F NMR (471
MHz, CDCl3) δ -74.2 (t, J = 8.0 Hz, 3F), 13C NMR (126 MHz, CDCl3) δ 197.6, 169.1,
146.7, 132.0, 129.7, 122.8 (q, J = 278.5 Hz), 120.4, 119.4, 109.5, 64.5 (q, J = 36.5
Hz), 36.2, 28.3, 25.2, 20.7. IR (KBr): 3071, 3055, 2969, 2934, 2895, 2876, 2837,
2227, 1642, 1616, 1503, 1466, 1431, 1377, 1365, 1295, 1235, 1213, 1172, 1158, 1115,
1086, 1056, 968, 856, 819, 762, 702, 666, 637 cm-1. HRMS-EI (m/z) calcd. for
C16H14F3NO2 ([M]+): 309.0977; Found: 309.0968.
2-(2-Chloro-4-fluorobenzyl)-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3g):
White solid, 88.9 mg, 66% yield (K2CO3 as the base). M.p.: 61-63 °C. 1H NMR (500
MHz, CDCl3) δ 7.07 (dd, J = 8.6, 2.5 Hz, 1H), 7.02 (dd, J = 8.0, 6.8 Hz, 1H), 6.83 (td,
J = 8.4, 2.4 Hz, 1H), 4.33 (q, J = 8.0 Hz, 2H), 3.73 (s, 2H), 2.59 (t, J = 6.0 Hz, 2H),
2.45 (t, J = 6.5 Hz, 2H), 2.10 (m, 2H). 19F NMR (471 MHz, CDCl3) δ -74.2 (t, J = 7.8
Hz, 3F), -116.1 (q, J = 8.0 Hz, 1F). 13C NMR (126 MHz, CDCl3) δ 197.7, 169.6,
160.8 (d, J = 246.6 Hz), 134.3 (d, J = 10.2 Hz), 133.8 (d, J = 3.5 Hz), 130.4 (d, J =
8.5 Hz), 122.8 (q, J = 278.5 Hz), 119.9, 116.4 (d, J = 24.5 Hz), 113.6 (d, J = 20.8 Hz),
64.4 (q, J = 36.5 Hz), 36.4, 25.3, 25.0, 20.8. IR (KBr): 3284, 3077, 2988, 2967, 2932,
2893, 2877, 2852, 1651, 1622, 1491, 1462, 1422, 1372, 1298, 1265, 1228, 1156, 1107,
1089, 1052, 1039, 988, 965, 925, 906, 879, 853, 808, 782, 741, 702, 687, 642 cm-1.
HRMS-EI (m/z) calcd. for C15H13F4O2 ([M ‒ Cl]+): 301.0852; Found: 301.0853.
2-(4-Methoxybenzyl)-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3h):
Yellow liquid, 91.8 mg, 73% yield. 1H NMR (500 MHz, CDCl3) δ 7.17 (d, J = 8.4 Hz,
2H), 6.76 (d, J = 8.5 Hz, 2H), 4.33 (q, J = 8.0 Hz, 2H), 3.75 (s, 3H), 3.57 (s, 2H), 2.51
(t, J = 6.1 Hz, 2H), 2.37 (t, J = 6.5 Hz, 2H), 2.01 (m, 2H). 19F NMR (471 MHz,
CDCl3) δ -74.1 (t, J = 8.0 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 198.0, 168.2, 157.7,
133.2, 129.9, 123.0 (q, J = 278.5 Hz), 122.3, 113.6, 64.4 (q, J = 36.5 Hz), 55.3, 36.4,
27.1, 25.2, 20.8. IR (KBr): 3100, 3061, 3032, 3000, 2954, 2875, 2837, 1660, 1649,
1624, 1584, 1511, 1458, 1428, 1370, 1287, 1245, 1226, 1160, 1110, 1089, 1051, 1034,
968, 921, 877, 853, 833, 816, 769, 726, 698, 668, 644 cm-1. HRMS-EI (m/z) calcd. for

C16H17F3O3 ([M]+): 314.1130; Found: 314.1137.
2-(Cyclohexylmethyl)-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3i):
Light yellow solid, 72.0 mg, 62% yield. M.p.: 93-95 °C. 1H NMR (500 MHz, CDCl3)
δ 4.33 (q, J = 8.0 Hz, 2H), 2.54 (t, J = 6.0 Hz, 2H), 2.38 (t, J = 6.5 Hz, 2H), 2.20 (d, J
= 7.1 Hz, 2H), 2.04 (m, 2H), 1.66 (m, 2H), 1.60-1.58 (m, 3H), 1.38 (m, 1H), 1.20-1.11
19
13
(m, 3H), 0.92 (m, 2H). F NMR (471 MHz, CDCl3) δ -74.3 (t, J = 8.0 Hz, 3F). C
NMR (126 MHz, CDCl3) δ 198.7, 168.1, 123.1 (q, J = 278.5 Hz), 121.6, 64.4 (q, J =
36.5 Hz), 37.2, 36.6, 33.3, 29.6, 26.7, 26.5, 25.3, 21.0. IR (KBr): 2922, 2848, 1637,
1615, 1448, 1427, 1375, 1351, 1305, 1295, 1255, 1230, 1213, 1190, 1163, 1130, 1087,
1053, 977, 922, 896, 869, 856, 710, 697, 674 cm-1. HRMS-EI (m/z) calcd. for
C15H21F3O2 ([M]+): 290.1494; Found: 290.1500.
2-Cinnamyl-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3j):
Yellow liquid, 93.7 mg, 72% yield. 1H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 7.7 Hz,
2H), 7.28 (t, J = 7.3 Hz, 2H), 7.18 (t, J = 7.2 Hz, 1H), 6.43 (d, J = 15.8 Hz, 1H),
6.22-6.16 (m, 1H), 4.38 (q, J = 8.0 Hz, 2H), 3.23 (d, J = 7.0 Hz, 2H), 2.54 (t, J = 6.0
Hz, 2H), 2.41 (t, J = 6.5 Hz, 2H), 2.06 (m, 2H). 19F NMR (471 MHz, CDCl3) δ -74.2
(t, J = 8.0 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 197.8, 168.6, 138.0, 130.5, 128.5,
127.7, 126.9, 126.1, 123.0 (q, J = 278.5 Hz), 120.4, 64.5 (q, J = 36.5 Hz), 36.4, 25.8,
25.3, 20.8. IR (KBr): 3082, 3060, 3027, 2951, 1719, 1649, 1623, 1495, 1453, 1424,
1372, 1287, 1228, 1163, 1095,1053, 1002, 966, 920, 855, 832, 754, 698, 665 cm-1.
HRMS-EI (m/z) calcd. for C17H17F3O2 ([M]+): 310.1181; Found: 310.1180.
5,5-Dimethyl-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3k):
White solid, 83.6 mg, 94% yield. M.p.: 66-68 °C. 1H NMR (400 MHz, CDCl3) δ 5.31
19
(s, 1H), 4.17 (q, J = 8.0 Hz, 2H), 2.36 (s, 2H), 2.22 (s, 2H), 1.08 (s, 6H). F NMR
13
(376 MHz, CDCl3) δ -73.6 (t, J = 7.8 Hz, 3F). C NMR (126 MHz, CDCl3) δ 199.0,
174.1, 122.7 (q, J = 277.2 Hz), 102.6, 65.0 (q, J = 36.5 Hz), 50.8, 42.3, 32.6, 28.3. IR
(KBr): 3077, 2966, 2947, 2879, 2831, 1741, 1665, 1623, 1471, 1452, 1431, 1418,
1374, 1325, 1285, 1264, 1212, 1183, 1166, 1144, 1123, 1051, 966, 921, 892, 871, 854,
831, 800, 692, 616 cm-1. HRMS-EI (m/z) calcd. for C10H13F3O2 ([M]+): 222.0868;
Found: 222.0871.

2-Benzyl-5,5-dimethyl-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3l):
Light yellow solid, 87.4 mg, 70% yield. M.p.: 51-53 °C. 1H NMR (500 MHz, CDCl3)
δ 7.24 (m, 4H), 7.15 (s, 1H), 4.33 (q, J = 7.5 Hz, 2H), 3.67 (s, 2H), 2.39 (s, 2H), 2.30
19
13
(s, 2H), 1.10 (s, 6H). F NMR (471 MHz, CDCl3) δ -74.2 (t, J = 7.5 Hz, 3F). C
NMR (126 MHz, CDCl3) δ 197.9, 166.7, 141.0, 128.8, 128.2, 125.7, 123.0 (q, J =
279.7 Hz), 120.9, 64.4 (q, J = 36.5 Hz), 50.3, 39.2, 32.5, 28.6, 27.9. IR (KBr): 3086,
3061, 3030, 2957, 2930, 2885, 2873, 2818, 1643, 1625, 1603, 1584, 1495, 1465, 1454,
1417, 1370, 1309, 1293, 1226, 1170, 1145, 1103, 1083, 991, 977, 927, 855, 779, 725,
699, 688, 649, 608 cm-1. HRMS-EI (m/z) calcd. for C17H19F3O2 ([M]+): 312.1337;
Found: 312.1335.
2-Allyl-5,5-dimethyl-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3m):
White solid, 61.3 mg, 58% yield. M.p.: 46-48 °C. 1H NMR (500 MHz, CDCl3) δ 5.75
(m, 1H), 4.98 (d, J = 17.0 Hz, 1H), 4.90 (d, J = 10.0 Hz, 1H), 4.33 (q, J = 8.0 Hz, 2H),
3.04 (d, J = 6.0 Hz, 2H), 2.37 (s, 2H), 2.25 (s, 2H), 1.09 (s, 6H). 19F NMR (471 MHz,
CDCl3) δ -74.4 (t, J = 8.0 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 197.7, 166.7, 135.7,
123.0 (q, J = 279.7 Hz), 119.4, 114.9, 64.5 (q, J = 36.5 Hz), 50.4, 39.3, 32.5, 28.6,
26.5. IR (KBr): 3086, 3024, 2962, 2940, 2910, 2896, 2876, 2832, 1639, 1620, 1459,
1430, 1375, 1305, 1294, 1224, 1164, 1131, 1095, 1070, 998, 970, 915, 885, 859, 761,
690, 672 cm-1. HRMS-EI (m/z) calcd. for C13H17F3O2 ([M]+): 262.1181; Found:
262.1190.
5-Methyl-3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3n):
Light yellow solid, 54.9 mg, 66% yield. M.p.: 44-46 °C. 1H NMR (500 MHz, CDCl3)
δ 5.29 (s, 1H), 4.16 (m, 2H), 2.52-2.41 (m, 2H), 2.24-2.19 (m, 2H), 2.04 (m, 1H), 1.08
(m, 3H). 19F NMR (471 MHz, CDCl3) δ -73.6 (t, J = 7.5 Hz, 3F). 13C NMR (126 MHz,
CDCl3) δ 199.0, 175.1, 122.7 (q, J = 278.5 Hz), 103.3, 65.0 (q, J = 36.5 Hz), 45.0,
36.5, 28.8, 20.8. IR (KBr): 3057, 2981, 2965, 2947, 2937, 2919, 2883, 2851, 2817,
1652, 1611, 1460, 1447, 1432, 1385, 1345, 1297, 1286, 1253, 1221, 1178, 1158, 1142,
1072, 1043, 968, 929, 877, 859, 694, 622 cm-1. HRMS-EI (m/z) calcd. for C9H11F3O2
([M]+): 208.0711; Found: 208.0702.
5-(2,2,2-Trifluoroethoxy)-1,6-dihydro-[1,1'-biphenyl]-3(2H)-one (3o):
White solid, 93.0 mg, 86% yield. M.p.: 95-97 °C. 1H NMR (500 MHz, CDCl3) δ 7.38

(m, 2H), 7.31-7.26 (m, 3H), 5.44 (s, 1H), 4.24 (m, 2H), 3.41 (s, 1H), 2.78-2.58 (m,
19
4H). F NMR (471 MHz, CDCl3) δ -73.5 (t, J = 7.2 Hz, 3F). 13C NMR (126 MHz,
CDCl3) δ 198.1, 174.8, 142.2, 129.0, 127.4, 126.8, 122.7 (q, J = 277.2 Hz), 103.6,
65.2 (q, J = 36.5 Hz), 43.9, 39.3, 36.1. IR (KBr): 3093, 3058, 3029, 2976, 2956, 2889,
2875, 1658, 1615, 1500, 1447, 1429, 1382, 1278, 1258, 1216, 1179, 1154, 1048, 1032,
965, 855, 811, 750, 695, 645 cm-1. HRMS-EI (m/z) calcd. for C14H13F3O2 ([M]+):
270.0868; Found: 270.0867.
3-(2,2,2-Trifluoroethoxy)cyclopent-2-en-1-one (3p):
Yellow oil, 46.1 mg, 64% yield. 1H NMR (400 MHz, CDCl3) δ 5.37 (s, 1H), 4.34 (q, J
19
= 8.0 Hz, 2H), 2.73 (m, 2H), 2.52 (m, 2H). F NMR (376 MHz, CDCl3) δ -73.7 (t, J
13
= 7.9 Hz, 3F). C NMR (126 MHz, CDCl3) δ 205.0, 188.1, 122.4 (q, J = 277.2 Hz),
106.1, 67.7 (q, J = 36.5 Hz), 34.5, 28.2. IR (KBr): 3087, 2962, 2940, 2926, 2853,
1712, 1697, 1680, 1609, 1459, 1440, 1411, 1367, 1301, 1274, 1247, 1228, 1190, 1164,
1039, 992, 967, 931, 859, 845, 832, 706 cm-1. HRMS-EI (m/z) calcd. for C7H7F3O2
([M]+): 180.0398; Found: 180.0394.
2-Methyl-3-(2,2,2-trifluoroethoxy)cyclopent-2-en-1-one (3q):
1
Yellow solid, 62.9 mg, 81% yield. M.p.: 42-44 °C. H NMR (400 MHz, CDCl3) δ
19
4.49 (q, J = 8.0 Hz, 2H), 2.63 (m, 2H), 2.49 (m, 2H), 1.66 (t, J = 1.7 Hz, 3H). F
13
NMR (376 MHz, CDCl3) δ -74.6 (t, J = 8.0 Hz, 3F). C NMR (126 MHz, CDCl3) δ
205.2, 180.8, 122.7 (q, J = 278.5 Hz), 118.9, 65.6 (q, J = 36.5 Hz), 33.7, 24.7, 6.08.
IR (KBr): 2963, 2927, 2858, 1733, 1692, 1644, 1445, 1387, 1352, 1284, 1235, 1164,
1123, 1071, 1028, 963, 885, 855, 834, 721, 675, 641 cm-1. HRMS-EI (m/z) calcd. for
C8H9F3O2 ([M]+): 194.0555; Found: 194.0549.
2-Benzyl-3-(2,2,2-trifluoroethoxy)cyclopent-2-en-1-one (3r):
Light yellow liquid, 98.4 mg, 91% yield. 1H NMR (500 MHz, CDCl3) δ 7.28-7.24 (m,
4H), 7.18 (m, 1H), 4.49 (q, J = 7.9 Hz, 2H), 3.51 (s, 2H), 2.66 (m, 2H), 2.52 (m, 2H).
19F NMR (471 MHz, CDCl3) δ -74.4 (t, J = 7.9 Hz, 3F). 13C NMR (126 MHz, CDCl3)
δ 203.7, 180.9, 139.3, 128.6, 128.4, 126.1, 122.6, 122.6 (q, J = 278.5 Hz), 65.5 (q, J =
36.5 Hz), 33.6, 27.3, 24.4. IR (KBr): 3088, 3062, 3033, 3010, 2918, 2850, 1681, 1623,
1495, 1456, 1432, 1289, 1253, 1239, 1171, 1097, 1075, 1047, 990, 965, 857, 840, 772,
720, 699, 682 cm-1. HRMS-EI (m/z) calcd. for C14H13F3O2 ([M]+): 270.0868; Found:

270.0872.
3-(2,2,2-Trifluoroethoxy)cyclohept-2-en-1-one (3s):
Colorless liquid, 4.9 mg, 6% yield, petroleum ether / ethyl acetate = 5 : 1 (v / v) as
eluents for column chromatography. 1H NMR (500 MHz, CDCl3) δ 5.33 (s, 1H), 4.10
(q, J = 7.9 Hz, 2H), 2.66 (t, J = 6.3 Hz, 2H), 2.62 (t, J = 6.4 Hz, 2H), 1.90 (m, 2H),
1.84 (m, 2H). 19F NMR (471 MHz, CDCl3) δ -73.7 (t, J = 8.0 Hz, 3F). 13C NMR (126
MHz, CDCl3) δ 201.5, 173.7, 122.7 (q, J = 278.5 Hz), 107.0, 65.1 (q, J = 36.5 Hz),
42.0, 32.5, 23.6, 21.3. IR (KBr): 2944, 2871, 1721, 1699, 1650, 1619, 1455, 1424,
1378, 1286, 1236, 1168, 1047, 976, 881, 817, 689 cm-1. HRMS-EI (m/z) calcd. for
C9H11F3O2 ([M]+): 208.0711; Found: 208.0716.
Methyl 3-(2,2,2-trifluoroethoxy)-1H-indene-2-carboxylate (3t):
White solid, 10.0 mg, 18% yield (Li2CO3) or 16.5 mg, 30% yield (Cs2CO3). M.p.:
80-82 °C. 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 7.3 Hz, 1H), 7.48-7.39 (m, 3H),
19
4.94 (q, J = 8.4 Hz, 2H), 3.85 (s, 3H), 3.71 (s, 2H). F NMR (471 MHz, CDCl3) δ
13
-75.1 (t, J = 8.6 Hz, 3F). C NMR (126 MHz, CDCl3) δ 164.6, 163.9, 141.7, 139.1,
129.2, 127.1, 124.4, 123.4 (q, J = 278.5 Hz), 121.0, 111.0, 70.8 (q, J = 35.5 Hz), 51.7,
36.4. IR (KBr): 2965, 2923, 2854, 1697, 1616, 1597, 1578, 1444, 1369, 1329, 1285,
1270, 1249, 1177, 1154, 1099, 1044, 958, 888, 851, 759, 719, 663 cm-1. HRMS-EI
(m/z) calcd. for C13H11F3O3 ([M]+): 272.0660; Found: 272.0655.
Methyl 1-oxo-2-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-indene-2-carboxylate (3t’):
1
Yellow liquid, 25.1mg, 46% yield (Li2CO3) or 12.9 mg, 24% yield (Cs2CO3). H
NMR (500 MHz, CDCl3) δ 7.81 (d, J = 7.7 Hz, 1H), 7.69 (t, J = 7.5 Hz, 1H), 7.56 (d,
J = 7.7 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 3.90 (d, J = 17.5 Hz, 1H), 3.73 (s, 3H), 3.35
(d, J = 17.5 Hz 1H), 3.33 (m, 1H), 2.66 (m, 1H). 19F NMR (471 MHz, CDCl3) δ -60.8
(t, J = 10.1 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 199.3, 169.3, 153.2, 136.1, 133.8,
128.2, 126.5, 126.1 (q, J = 278.5 Hz), 125.3, 57.3 (q, J = 1.7 Hz), 53.6, 37.8 (q, J =
29.0 Hz), 35.4 (q, J = 1.7 Hz). IR (KBr): 3084, 3039, 3005, 2957, 2848, 1748, 1716,
1609, 1590, 1466, 1435, 1374, 1303, 1258, 1206, 1172, 1141, 1111, 1047, 1015, 970,
957, 926, 864, 842, 813, 785, 752, 697, 652, 600, 577 cm-1. HRMS-EI (m/z) calcd. for
C13H11F3O3 ([M]+): 272.0660; Found: 272.0668.

Methyl
5,6-dimethoxy-1-oxo-2-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-indene-2-car-boxylate
(3u’):
White solid, 43.0 mg, 43% yield, petroleum ether / ethyl acetate = 2 : 1 (v / v) as
eluents for column chromatography. M.p.: 160-162 °C. 1H NMR (500 MHz, CDCl3) δ
7.17 (s, 1H), 6.94 (s, 1H), 4.00 (s, 3H), 3.91 (s, 3H), 3.78 (d, J = 17.1 Hz, 1H), 3.72 (s,
3H), 3.30 (m, 1H), 3.24 (d, J = 17.1 Hz, 1H), 2.62 (m, 1H). 19F NMR (471 MHz,
CDCl3) δ -60.9 (t, J = 10.7 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 197.4, 169.5,
156.6, 150.0, 148.8, 126.2, 126.1 (q, J = 278.5 Hz), 107.2, 105.2, 57.4 (q, J = 1.5 Hz),
56.4, 56.1, 53.3, 37.7 (q, J = 29.0 Hz), 35.0 (q, J = 1.8 Hz). IR (KBr): 3010, 2960,
2917, 2880, 2839, 1717, 1595, 1504, 1467, 1456, 1444, 1425, 1363, 1320, 1282, 1253,
1221, 1176, 1144, 1117, 1101, 1025, 965, 901, 880, 865, 761, 670, 641 cm-1.
HRMS-EI (m/z) calcd. for C15H15F3O5 ([M]+): 332.0872; Found: 332.0873.
(Z)-1,3-diphenyl-3-(2,2,2-trifluoroethoxy)prop-2-en-1-one (3v):
White solid, 11.4 mg, 19% yield (Li2CO3) or 28.3 mg, 46% yield (Cs2CO3). M.p.:
79-81 oC. 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 7.6 Hz, 2H), 7.80 (d, J = 7.6 Hz,
2H), 7.61 (t, J = 7.5 Hz, 1H), 7.56-7.47 (m, 5H), 6.78 (s, 1H), 4.59 (q, J = 8.4 Hz, 2H).
19F NMR (471 MHz, CDCl3) δ -74.2 (t, J = 8.4 Hz, 3F). 13C NMR (126 MHz, CDCl3)
δ 189.0, 167.0, 139.0, 134.9, 133.0, 131.6, 128.9, 128.8, 128.5, 127.8, 123.4 (q, J =
278.5 Hz), 103.0, 70.8 (q, J = 36.5 Hz). IR (KBr): 3088, 3064, 3005, 2960, 2880,
1646, 1599, 1585, 1569, 1489, 1450, 1417, 1370, 1266, 1216, 1165, 1129, 1045, 1026,
984, 966, 906, 850, 832, 796, 765, 705, 696, 689, 603 cm-1. HRMS-EI (m/z) calcd. for
C17H13F3O2 ([M]+): 306.0868; Found: 306.0865.
1,3-Diphenyl-2-(2,2,2-trifluoroethyl)propane-1,3-dione (3v’):
White solid, 42.5 mg, 69% yield (Li2CO3) or 29.1 mg, 48% (Cs2CO3). M.p.: 49-51 oC.
1H NMR (500 MHz, CDCl3) δ 7.96 (d, J = 7.9 Hz, 4H), 7.59 (t, J = 7.4 Hz, 2H), 7.46
(t, J = 7.9 Hz, 4H), 5.59 (t, J = 6.1 Hz, 1H), 3.05 (m, 2H). 19F NMR (471 MHz,
CDCl3) δ -64.9 (t, J = 10.1 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 193.3, 135.3,
134.2, 129.2, 128.9, 126.4 (q, J = 277.2 Hz), 50.3 (q, J = 1.9 Hz), 33.2 (q, J = 30.2
Hz). IR (KBr): 3064, 3028, 3010, 2957, 2927, 1701, 1670, 1643, 1630, 1597, 1493,
1449, 1431, 1357, 1332, 1257, 1150, 1113, 1086, 1072, 1020, 963, 944, 927, 839, 775,
747, 688 cm-1. HRMS-EI (m/z) calcd. for C17H13F3O2 ([M]+): 306.0868; Found:

306.0871.
1-(4-methoxyphenyl)-3-phenyl-2-(2,2,2-trifluoroethyl)propane-1,3-dione (3w’):
1
Colorless liquid, 20.6 mg, 31% yield. H NMR (500 MHz, CDCl3) δ 7.96-7.94 (m,
4H), 7.58 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 5.51 (t,
J = 6.1 Hz, 1H), 3.84 (s, 3H), 3.03 (dm, J = 57.1 Hz, 2H). 19F NMR (471 MHz,
CDCl3) δ -64.9 (t, J = 10.1 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 193.3, 191.6,
164.3, 135.4, 133.9, 131.2, 129.0, 128.7, 128.0, 126.4 (q, J = 277.2 Hz), 114.3, 55.6,
50.1 (q, J = 1.8 Hz), 33.2 (q, J = 30.1 Hz). IR (KBr): 3064, 2962, 2923, 2847, 1731,
1696, 1669, 1600, 1575, 1512, 1449, 1422, 1379, 1337, 1318, 1261, 1226, 1199, 1172,
1145, 1111, 1028, 964, 847, 801, 759, 742, 688 cm-1. HRMS-EI (m/z) calcd. for
C18H15F3O3 ([M]+): 336.0973; Found: 336.0970.
1-Phenyl-2-(2,2,2-trifluoroethyl)butane-1,3-dione (3x’):
1
Colorless liquid, 49.8 mg, 68% yield. H NMR (500 MHz, CDCl3) δ 8.04 (d, J = 7.5
Hz, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.55 (t, J = 7.7 Hz, 2H), 4.85 (t, J = 6.4 Hz, 1H),
19
2.92 (dm, J = 52.2 Hz, 2H), 2.18 (s, 3H). F NMR (471 MHz, CDCl3) δ -65.0 (t, J =
10.7 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 199.7, 193.9, 135.5, 134.4, 129.2, 128.9,
126.2 (q, J = 277.2 Hz), 55.9 (q, J = 1.8 Hz), 32.7 (q, J = 29.9 Hz), 28.6. IR (KBr):
3066, 3008, 2964, 2929, 2856, 1731, 1682, 1596, 1581, 1449, 1434, 1362, 1336, 1264,
1210, 1146, 1113, 1079, 1069, 1018, 1001, 968, 932, 866, 831, 774, 754, 694, 669,
652, 637, 611 cm-1. HRMS-EI (m/z) calcd. for C12H11F3O2 ([M]+): 244.0711; Found:
244.0707.
1-Phenyl-2-(2,2,2-trifluoroethyl)pentane-1,3-dione (3y’):
1
Colorless liquid, 43.5 mg, 56% yield (Li2CO3) or 50.3 mg, 65% yield (Cs2CO3). H
NMR (500 MHz, CDCl3) δ 8.03 (d, J = 7.5 Hz, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.56 (t, J
= 7.8 Hz, 2H), 4.87 (t, J = 6.4 Hz, 1H), 2.93 (dm, J = 55.1 Hz, 2H), 2.49 (q, J = 7.2
Hz, 2H), 1.03 (t, J = 7.2 Hz, 3H). 19F NMR (471 MHz, CDCl3) δ -65.0 (t, J = 10.0 Hz,
3F). 13C NMR (126 MHz, CDCl3) δ 202.4, 194.1, 135.7, 134.3, 129.2, 128.9, 126.3 (q,
J = 277.2 Hz), 54.9 (q, J = 1.8 Hz), 35.2, 32.8 (q, J = 29.8 Hz), 7.6. IR (KBr): 3065,
2982, 2943, 2909, 2880, 1729, 1682, 1628, 1596, 1493, 1449, 1433, 1410, 1380, 1334,
1278, 1260, 1148, 1106, 1059, 1035, 1001, 967, 936, 835, 775, 703, 688 cm-1.
HRMS-ESI (m/z) calcd. for C12H11F3O2 ([M + H]+): 259.0946; Found: 259.0952.

Diethyl 2-(2,2,2-trifluoroethyl)malonate (3z’) 17a
:
1
Colorless liquid, 50.9 mg, 42% yield. H NMR (500 MHz, CDCl3) δ 4.26 (q, J = 7.0
19
Hz, 4H), 3.65 (t, J = 7.0 Hz, 1H), 2.83 (m, 2H), 1.30 (t, J = 7.0 Hz, 6H). F NMR
(471 MHz, CDCl3) δ -65.9 (t, J = 10.1 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 167.5,
125.9 (q, J = 277.2 Hz), 62.4, 46.4 (q, J = 2.7 Hz), 33.2 (q, J = 30.2 Hz), 14.1.
Dibenzyl 2-(2,2,2-trifluoroethyl)malonate (3aa’) 17b
:
1
Colorless liquid, 94.0 mg, 51% yield. H NMR (500 MHz, CDCl3) δ 7.39-7.37 (m,
6H), 7.32 (m, 4H), 5.22 (m, 4H), 3.81 (t, J = 7.0 Hz, 1H), 2.90 (m, 2H). 19F NMR
(471 MHz, CDCl3) δ -65.7 (t, J = 10.5 Hz, 3F). 13C NMR (126 MHz, CDCl3) δ 167.1,
134.8, 128.7, 128.6, 128.3, 125.8 (q, J = 277.2 Hz), 68.0, 46.3 (q, J = 2.5 Hz), 33.0 (q,
J = 30.3 Hz).
Acknowledgements
We thank the Wuhan University of Technology, the Fundamental Research Funds for
the Central Universities, the National Natural Science Foundation of China
(21602165), the “Chutian Scholar” Program from Department of Education of Hubei
Province (China), the “Hundred Talent” Program of Hubei Province, and the Wuhan
Youth Chen-Guang Project (2016070204010113) for financial support.
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The
pKa
values
of
1,3-dicarbonyl
compounds
see:
http://www.chem.wisc.edu/areas/reich/pkatable/index.htm.
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Figures
Scheme 1. The previous examples of carbon-specific trifluoroethylation and
perfluoroethylation of 1,3-dicarbonyls

Table
1
Trifluoroethylation
of
cyclohexane-1,3-dione
(1a)
by
mesityl(2,2,2-trifluoroethyl)iodonium triflate (2a) in different conditions
Entry a
Base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Li2CO3
NaHCO3
Cs2CO3
Li2CO3
Li2CO3
Li2CO3
Solvent
CH2Cl2
CH3CN
THF
Yield (3a, %) b
1
2
61
75
3
3
4
DMF
23
5
DMSO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
24
6
78
7
89
8
74
9
77
10 c
11 d
12 d,e
94 (72)
99 (83)
(80)
a Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), base (0.2 mmol), solvent (2
b
mL), r.t., N2, overnight.
The yields were determined by HPLC using
3-(2,2,2-trifluoroethoxy)cyclohex-2-en-1-one (3a) as an external standard (tR = 3.0

min, λmax = 244.1 nm, water/methanol = 30 : 70 (v / v)). Isolated yield was depicted in
c
d
the parentheses.
2a (0.12 mmol), Li2CO3 (0.15 mmol).
2a (0.15 mmol),
e
Li2CO3 (0.15 mmol).
[PhICH2CF3][OTf] (2b) was used instead of
[MesICH2CF3][OTf] (2a).
Table 2. O-Trifluoroethylation of cyclic 1,3-diketones by 2a [a]
a
Reaction conditions: 1 (0.4 mmol), 2a (0.6 mmol), Li2CO3 (0.6 mmol), CH3CN (2
b
c
mL), r.t., N2, overnight. Isolated yields.
K2CO3 was used instead of Li2CO3.
Yield was determined by 19F NMR spectroscopy using trifluoromethoxybenzene as an
internal standard.
Table 3. C- or C/O-Trifluoroethylation of acyclic 1,3-dicarbonyls by 2aa

a
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), base (0.3 mmol), 4Å MS (100
b
19
mg), CH3CN (2 mL), r.t., N2, 24 h. Isolated yield.
Yield was determined by F
NMR spectroscopy using trifluoromethoxybenzene as an internal standard.
c 1 (0.3
d
mmol), 2a (0.6 mmol), base (0.45 mmol), 4Å MS (100 mg), 24 h. Isolated yield.
1 (1.5 mmol), 2a (0.5 mmol), KOH (0.55 mmol), 4Å MS (100 mg), 24 h. Isolated
yield.