Trifluoromethylation of alkenes by visible light photoredox catalysis

Article abstract of DOI:10.1021/jo3022346

A method for trifluoromethylation of alkenes has been developed employing visible light photoredox catalysis with CF₃I, Ru(Phen) ₃Cl₂, and DBU. This process works especially well for terminal alkenes to give alkenyl-CF₃ products with only E-stereochemistry. The mild reaction conditions enable the trifluoromethylation of a range of alkenes that bear various functional groups.

Full text of DOI:10.1021/jo3022346

Note
pubs.acs.org/joc
Trifluoromethylation of Alkenes by Visible Light Photoredox
Catalysis
Naeem Iqbal, Sungkyu Choi, Eunjin Kim, and Eun Jin Cho*
Department of Chemistry and Applied Chemistry, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, ansan, Kyeonggi-do
426-791, Republic of Korea
S
* Supporting Information
ABSTRACT: A method for trifluoromethylation of alkenes has
been developed employing visible light photoredox catalysis
with CF3I, Ru(Phen)3Cl2, and DBU. This process works
especially well for terminal alkenes to give alkenyl-CF3 products
with only E-stereochemistry. The mild reaction conditions
enable the trifluoromethylation of a range of alkenes that bear
various functional groups.
he trifluoromethylation of organic molecules is of vital
importance in the fields of pharmaceuticals and agro-
ppy)2(dtbbpy)]PF6 in DMF/H2O with 48 h reaction time or 1
mol % of Ru(bpy)3Cl2/0.35 equiv of Na ascorbate in CH3CN/
MeOH with 48 h reaction time as useful examples of atom-
transfer radical additions.9 On the basis of these iodotrifluor-
omethylations and our previously reported trifluoromethylation
of heterocycles10 of the photocatalysis, we commenced our
investigation with 1-dodecene as a model compound employing
our previous reductive quenching pathway conditions. With
CF3I, TMEDA (or TEA), and Ru(bpy)3Cl2 in CH3CN,
trifluoromethylated alkyl iodide was obtained in excellent
yield within 20 min with merely 0.01 mol % of Ru(bpy)3Cl2
under a 14 W household lamp (Scheme 1 (1)). Based on this
encouraging result, we hypothesized that alkenyl−CF3 products
can be generated by employing a base that can potentially act
both as a reductive quencher for the photocatalysis and as a
base11 for the hydrogen iodide elimination from 2a. For the
elimination, Ha could be selectively eliminated over Hb due to
T
chemicals since inclusion of a CF3 moiety into organic
molecules can result in enhanced lipophilicity, metabolic
stability, bioavailability, and binding selectivity.1 A variety of
nucleophilic, electrophilic, and radical processes for C−CF3
bond formation have been reported,1d,2 including several
transition-metal-catalyzed methods3,4 that directly form
Csp2−CF3 bonds. However, these methods are mainly limited
to the formation of aryl−CF3 bonds. Only a limited number of
processes for the construction of alkenyl−CF3 bonds are
currently available (Figure 1 (1)).5 In addition, the known
Scheme 1. Trifluoromethylation via Visible Light
Photocatalysis
Figure 1. Alkenyl trifluoromethylations.
alkenyl trifluoromethylation methods have some limitations.
They not only have a narrow scope but also require
prefunctionalized substrates. The lack of E/Z selectivity is
another shortcoming with some of these methods. Herein, we
report a radical-based trifluoromethylation of unactivated
alkenes via visible light photoredox catalysis6,7 that shows a
broad substrate scope and high E/Z selectivity (Figure 1 (2)).
Radical-based halotrifluoromethylations of alkenes using
CF3I or CF3SO2Cl as the CF3 radical sources had been
developed by several groups.8 More recently, Stephenson and
co-workers provided trifluoroalkylated alkyl iodides by visible
light-induced photocatalysis, using 1 mol % of [Ir(dF(CF3)-
Received: October 14, 2012
© XXXX American Chemical Society
A
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Note
its lower pKa resulting from a highly electron-withdrawing
nature of the trifluoromethyl group.12 Several bases including
DIPEA and DBU were examined, and the use of DBU in the
reaction of 1-dodecene 1a generated alkenyl−CF3 product 3a
in good yield and excellent regio- and E/Z selectivity (Scheme
1 (2)). Allyl-CF3 product 4a13 from the Hb elimination was
barely formed (2−3%). No detectable amounts of Z-isomers of
both 3a and 4a were observed in the reaction.
Table 2. Scope of the Trifluoromethylation of Terminal
Alkenes
a
With these promising initial results, we further optimized the
reaction conditions. First, various Ru and Ir photocatalysts were
evaluated. We found that besides Ru(bpy)3Cl2, a range of Ru or
Ir photocatalysts such as Ir(ppy)3, Ir(ppy)2(dtb-bpy)PF6, and
Ru(phen)3Cl2 were also effective for the reaction. Among them,
14a
Ru(phen)3Cl2 was chosen for further studies because of its
lower cost and cleaner reaction profile. In addition, control
experiments showed that both the photocatalyst and visible
light are required for the transformation.
Next, we examined the effect of other parameters on the
reaction, including solvents, concentration, and the stoichiom-
etry of reagents (Table 1). CH3CN was found to be the most
Table 1. Optimization Studies for the Trifluoromethylation
a
of 1-Dodecene
Ru(phen)3Cl2
(mol %)
b
entry
DBU (equiv)
solvent
product yield (%)
1
2
3
4
5
6
0.5
0.5
0.5
0.5
0.5
0.1
0.01
2.0
2.0
2.0
1.0
1.5
2.0
2.0
CH2Cl2
DMF
80
76
96
80
89
96
90
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
c
7
a
Reaction conditions: 1a (0.2 mmol), CF3I (0.6 mmol), Ru-
b
(phen)3Cl2, DBU, solvent (0.4 mL). The yield was determined by
c
19F NMR spectroscopy with 4-fluorotoluene as an internal standard. 4
h reaction time.
effective solvent, although the reaction could be carried out in
other solvents such as CH2Cl2 and DMF (entries 1−3).
Reaction concentration also affected the efficiency, and 0.5 M
in CH3CN afforded the best result. An excess amount (2 equiv)
of DBU was required for the maximum yield, and inferior
results were obtained with less than 2 equiv of DBU despite a
full conversion (entries 3−5). The use of at least 2 equiv of
CF3I was also required for reproducible results. Notably, an
extremely low photocatalyst loading (0.01 mol %) was enough
for full conversion and high product yields (entries 3, 6, and 7),
showing the efficacy of this catalytic process.
With the optimized conditions in hand, the reactions of a
variety of terminal alkenes were explored (Table 2). The mild
reaction conditions allowed trifluoromethylation of alkenes
containing a range of functional groups, including unprotected
alcohol (3b, 3m), aldehyde (3c), ketone (3d), ester (3e, 3f),
carbamate (3g), amide (3h, 3i, 3j), silyl ether (3k), sulfonates
(3l), and aryl halides such as aryl bromide (3i) and aryl
chloride (3j). Notably, aromatic systems appeared to be
inactive under the reaction conditions.15 In most cases, a
trace amount (2−4%) of allyl-CF3 products were produced. In
a
Reaction conditions: 1 (1.0 mmol), CF3I (2.0−3.0 mmol),
Ru(phen)3Cl2 (0.001 mmol), DBU (2.0 mmol), CH3CN (2 mL),
2−10 h. Isolated yield based on an average of two runs. 17:1 ratio
with the allyl-CF3 product.
b
c
addition to allyl-CF3 products, to a minor extent (<5%)
trifluoromethylated alkyl iodides (such as 2a shown in Scheme
1) or bis-trifluoromethylation products from further reactions
of alkenyl-CF3 products were also observed. The current
reaction conditions were amenable to a large scale reaction such
B
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Note
that alkenyl-CF3 product 3a was prepared on a 5 mmol scale
with yield similar to that of a 1 mmol scale reaction.
Scheme 3. Trifluoromethylation of Internal Alkenes
Besides high regio- and stereroselectivity, another salient
feature of this transformation is the lower reactivity of the
trifluoromethylated alkene toward the second trifluoromethy-
lation, resulting in the monotrifluoromethylation. In the
reaction of a mixture of 1a and isolated 3a, only 1a selectively
participated in the transformation (Scheme 2 (1)). The
Scheme 2. Trifluoromethylation of Alkenes
Figure 2. Proposed mechanism of the alkenyl trifluoromethylation.
trifluoromethylated secondary carbon radical 9. The reaction of
this radical can proceed to generate alkenyl-CF3 products by
three possible pathways:17 (a) radical propagation, (b)
oxidation18 followed by nucleophilic iodide attack, or (c)
oxidation followed by Ha abstraction by a base. Pathway c
would be less likely because E-alkenes seems to be
predominantly generated via E2 elimination of HI from
trifluoromethylated alkyl iodide intermediates as shown in
Figure 2.
In conclusion, we have developed a visible light-induced
trifluoromethylation for alkenes, providing a direct method to
access trifluoromethylated alkenes without prefunctionalization.
This process works especially well for terminal alkenes to give
alkenyl-CF3 over allyl-CF3 products with only E-stereo-
chemistry. Mild reaction conditions enable the trifluoromethy-
lation of a broad range of alkenes bearing various functional
groups.
reaction of methyl acrylate 1o also supported that electron-
deficient alkenes are less reactive toward the trifluoromethyla-
tion, providing significantly lower yield of 3o (55%) (Scheme 2
(2)).16 Interestingly, the reaction of allylbenzene 1p provided
allyl-CF3 product 4p by selective elimination of benzylic
hydrogen (Scheme 2 (3)). The formation of a conjugated
system is likely the driving force for this allyl trifluoromethy-
lation. The reaction of β-pinene 5 gave a ring-opened diene 6 as
the major product through the radical rearrangement from I to
II after the addition of *CF3 radical to the alkene as shown in
Scheme 2 (4).
Although the reactions of terminal alkenes are regio- and
stereoselective, those of internal alkenes generated a mixture of
isomers. The reaction of a symmetrical alkene, trans-5-decene
7a, provided a mixture of E- and Z-isomers in 80% yield
(Scheme 3 (1)). With cyclic alkene 7b, the reaction provided a
mixture of the desired alkenyl-CF3 product 8b and trifluor-
omethylated alkyl iodide trans-7b′ due to a limited C−C bond
rotation in the cyclic system (Scheme 3 (2)).16
EXPERIMENTAL SECTION
■
Experimental Procedure for the Iodotrifluoromethylation of
1a. An oven-dried resealable test tube equipped with a magnetic stir
bar was charged with 1-dodecene 1a (1.0 mmol), sealed with a silicone
septa screw cap, and degassed by alternating vacuum evacuation and
argon backfill. A solution of Ru(bpy)3Cl2 (0.01 mol %, 0.0001 mmol)
in CH3CN (4.0 mL, 0.25 M) and TMEDA (2.0 mmol) were then
added to the tube under argon. CF3I (3.0 mmol) was then bubbled
into the reaction mixture using a gastight syringe. The test tube was
placed under a 14 W household light bulb at room temperature. The
reaction was allowed to proceed for 20 min, and reaction progress was
checked by TLC. The reaction mixture was then diluted with diethyl
ether and washed with water and brine. The organic layers were dried
Based on these results, we propose a plausible mechanism of
the transformation in Figure 2. We assume that the excitation
of Ru(phen)32+ by visible light provides Ru(phen)32+*, which is
then reductively quenched by DBU to produce Ru(phen)3+ and
+
the ammonium radical cation. The Ru(phen)3 (Eoxi [Ru-
14a
+
(phen)3 /Ru(phen)32+] = +1.41 V vs SCE in CH3CN) in
turn performs a single-electron reduction of the F3C−I (1.22 V
vs SCE in CH3CN)14b bond, regenerating Ru(phen)3 and
2+
forming a carbon-centered *CF3 radical. Addition of this
electron-deficient radical species with an alkene generates the
C
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Note
over MgSO4, concentrated in vacuo, and purified by flash column
chromatography (hexanes/Et2O) to give 1,1,1-trifluoro-3-iodotride-
cane 2a as a colorless oil in 95% (346 mg): H NMR (400 MHz,
28.2, 25.2, 24.6, 22.8, 14.2; IR (neat): νmax = 2932, 2859, 1737, 1682,
1274, 1121 cm−1; HRMS (EI) calcd for C15H25F3O2 294.1807, found
294.1805; Rf 0.58 (hex/EtOAc, 8/1).
1
CDCl3) δ 4.24−4.16 (m, 1H), 2.98−2.70 (m, 2H), 1.85−1.68 (m,
2H), 1.59−1.47 (m, 1H), 1.45−1.22 (m, 15H), 0.89 (t, J = 7.2 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 125.8 (q, J = 279.8 Hz), 45.2 (q,
J = 28.2 Hz), 39.9, 32.1, 29.8, 29.8, 29.7, 29.6, 29.6, 28.8, 22.9, 22.0 (q,
J = 2.7 Hz), 14.3; IR (neat) νmax = 2926, 2856, 1256, 1149 cm−1;
HRMS (EI) calcd for C13H24F3I 364.0875, found 364.0877; Rf 0.90
(only hexanes).
General Experimental Procedure for the Trifluoromethyla-
tion of Alkenes. An oven-dried resealable test tube equipped with a
magnetic stir bar was charged with an alkene (1.0 mmol), sealed with a
silicone septa screw cap, and degassed by alternating vacuum
evacuation and argon backfill. A solution of Ru(phen)3Cl2·xH2O
(0.1 mol %, 0.001 mmol) in CH3CN (2.0 mL, 0.5 M) and DBU (2.0
mmol) were then added to the tube under argon. CF3I (2.0 mmol-3.0
mmol) was then bubbled into the reaction mixture using a gastight
syringe. The test tube was placed under a 14 W household light bulb at
room temperature. The reaction was allowed to proceed for 2−10 h,
and reaction progress was checked by TLC or gas chromatography.
The reaction mixture was then diluted with diethyl ether and washed
with water and brine. The organic layers were dried over MgSO4,
concentrated in vacuo, and purified by flash column chromatography
(hexanes/EtOAc or hexanes/Et2O) to give the trifluoromethylated
alkene.
Analytic Data for Trifluoromethylated Alkenes. (E)-1,1,1-
Trifluorotridec-2-ene (3a): colorless oil (224 mg, 95%); 1H NMR
(400 MHz, CDCl3) δ 6.38 (dtq, J = 15.8, 6.8, 2.0 Hz, 1H), 5.60 (dqt, J
= 15.8, 6.4, 1.6 Hz, 1H), 2.19−2.10 (m, 2H), 1.47−1.39 (m, 2H),
1.33−1.24 (m, 14H), 0.88 (t, J = 6.4 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 141.0 (q, J = 6.4 Hz), 123.4 (q, J = 270.0 Hz), 118.6 (q, J =
33.2 Hz), 32.2, 31.7, 29.9, 29.8, 29.7, 29.6, 29.3, 28.3, 23.0, 14.3; 19F
NMR (377 MHz, CDCl3) δ −64.27; IR (neat) νmax = 2928, 2857,
1273, 1122 cm−1; HRMS (EI) calcd for C13H23F3 236.1752, found
236.1750; Rf 0.95 (only hexanes).
(E)-7,7,7-Trifluorohept-5-en-1-yl benzoate (3f): colorless oil (253
mg, 93%); H NMR (400 MHz, CDCl3) δ 7.41−8.07 (m, 5H), 6.39
1
(dtq, J = 16.0, 6.8, 2.0 Hz, 1H), 5.64 (dqt, J = 16.0, 6.4, 1.6 Hz, 1H),
2.27−2.18 (m, 2H), 1.84−1.76 (m, 2H), 1.65−1.57 (m, 2H); 13C
NMR (101 MHz, CDCl3) δ 166.8, 140.4 (q, J = 6.5 Hz), 133.1, 130.5,
129.7, 128.6, 123.2 (q, J = 270.0 Hz), 119.0 (q, J = 33.3 Hz), 64.6,
31.2, 28.3, 24.7; 19F NMR (377 MHz, CDCl3) δ −63.97; IR (neat):
νmax = 2946, 1720, 1681, 1275, 1117 cm−1; HRMS (EI) calcd for
C14H15F3O2 272.1024, found 272.1026; Rf 0.50 (hex/EtOAc, 8/1) .
(E)-7,7,7-Trifluorohept-5-en-1-yl dimethylcarbamate (3g): color-
less oil (192 mg, 80%); 1H NMR (400 MHz, CDCl3) δ 6.35 (dtq, J =
16.0, 6.8, 1.6 Hz, 1H), 5.61 (dqt, J = 16.0, 6.4, 1.6 Hz, 1H), 4.06 (t, J =
6.4 Hz, 2H), 2.89 (s, 6H), 2.23−2.13 (m, 2H), 1.69−1.61 (m, 2H),
1.56−1.46 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 156.9, 140.4 (q, J
= 6.5 Hz), 123.2 (q, J = 269.9 Hz), 118.9 (q, J = 33.3 Hz), 65.0, 36.5,
36.0, 31.2, 28.7, 24.6; 19F NMR (377 MHz, CDCl3) δ −64.00; IR
(neat) νmax = 2940, 1704, 1403, 1188, 1117 cm−1; HRMS (EI) calcd
for C10H16F3NO2 239.1133, found 239.1135; Rf 0.28 (hex/EtOAc, 8/
1).
(E)-N-(4,4,4-Trifluorobut-2-en-1-yl)octanamide (3h): colorless oil
1
(214 mg, 85%); H NMR (400 MHz, CDCl3) δ 6.35 (dtq, J = 15.6,
6.8, 2.0 Hz, 1H), 6.14 (bs, 1H), 5.70 (dqt, J = 15.6, 6.4, 1.8 Hz, 1H),
4.01−3.94 (m, 2H), 2.21 (t, J = 7.6 Hz, 2H), 1.62 (tt, J = 7.6, 7.6 Hz,
2H), 1.34−1.20 (m, 8H), 0.86 (t, J = 6.8 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 173.6, 136.9 (q, J = 6.3 Hz), 123.0 (q, J = 270.28 Hz),
119.3 (q, J = 34.14 Hz), 39.5, 36.7, 31.8, 29.4, 29.2, 25.9, 22.8, 14.2;
19F NMR (377 MHz, CDCl3) δ −64.21; IR (neat): νmax = 3289, 2930,
2859, 1651, 1547, 1124 cm−1; HRMS (EI) calcd for C12H20F3NO
251.1497, found 251.1500; Rf 0.28 (hex/EtOAc, 2/1).
(E)-4-Bromo-N-(4,4,4-trifluorobut-2-en-1-yl)benzamide (3i): white
solid (256 mg, 83%); 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.6
Hz, 2H), 7.55 (d, J = 8.6 Hz, 2H), 6.78 (bs, 1H), 6.42 (dtq, J = 15.6,
5.2, 2.0 Hz, 1H), 5.76 (dqt, J = 15.6, 6.0, 1.8 Hz, 1H), 4.18−4.12 (bs,
2H); 13C NMR (101 MHz, CDCl3) δ 166.9, 136.4 (q, J = 6.3 Hz),
132.7, 132.1, 128.8, 126.9, 122.9 (q, J = 270.5 Hz), 119.8 (q, J = 34.2
(E)-7,7,7-Trifluorohept-5-en-1-ol (3b): colorless oil (135 mg, 80%);
1H NMR (400 MHz, CDCl3) δ 6.36 (dtq, J = 16.0, 6.8, 2.0 Hz, 1H),
5.61 (dqt, J = 16.0, 6.4, 1.6 Hz, 1H), 3.37 (t, J = 6 Hz, 2H), 2.22−2.15
(m, 2H), 1.92 (bs, 1H), 1.61−1.47 (m, 4H); 13C NMR (101 MHz,
CDCl3) δ 140.5 (q, J = 6.6 Hz), 123.2 (q, J = 269.9 Hz), 118.8 (q, J =
33.3 Hz), 62.5, 32.1, 31.3, 24.4; 19F NMR (377 MHz, CDCl3) δ
−60.34; IR (neat) νmax = 3347, 2939, 1681, 1275, 1121 cm−1.
(E)-12,12,12-Trifluorododec-10-enal (3c): colorless oil (184 mg,
Hz), 40.2; 19F NMR (377 MHz, CDCl3) δ −64.14; IR (neat) νmax
=
3317, 1651, 1541, 1302, 1275, 1111 cm−1; HRMS (EI) calcd for
C11H9BrF3NO 306.9820, found 306.9816; Rf 0.35 (hex/EtOAc, 2/1).
(E)-4-Chloro-N-(4,4,4-trifluorobut-2-en-1-yl)benzamide (3j): white
solid (208 mg, 79%); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.8
Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 6.79 (bs, 1H), 6.42 (dtq, J = 15.8,
5.2, 2.0 Hz, 1H), 5.76 (dqt, J = 15.8, 6.4, 1.8 Hz, 1H), 4.18−4.12 (bs,
2H); 13C NMR (101 MHz, CDCl3) δ 166.8, 138.5, 136.4 (q, J = 6.4
Hz), 132.3, 129.2, 128.6, 122.9 (q, J = 270.4 Hz), 119.9 (q, J = 34.3
1
78%); H NMR (400 MHz, CDCl3) δ 9.76 (t, J = 1.8 Hz, 1H), 6.37
(dtq, J = 15.6, 6.8, 2.0 Hz, 1H), 5.60 (dqt, J = 15.6, 6.4, 1.8 Hz, 1H),
2.42 (td, J = 7.4, 1.8 Hz, 2H), 2.19−2.08 (m, 2H), 1.67−1.58 (m, 2H),
1.47−1.37 (m, 2H), 1.36−1.26 (m, 8H); 13C NMR (101 MHz,
CDCl3) δ 203.1, 140.9 (q, J = 6.5 Hz), 123.3 (q, J = 270.2 Hz), 118.6
(q, J = 33.2 Hz), 44.1, 31.6, 29.4, 29.3, 29.3, 29.1, 28.1, 22.2; 19F NMR
(377 MHz, CDCl3) δ −63.89; IR (neat) νmax = 2931, 2858, 1727,
1681, 1274, 1119 cm−1; HRMS (EI) calcd for C12H19F3O 236.1388,
found 236.1390; Rf 0.53 (hex/EtOAc, 8/1).
(E)-13,13,13-Trifluorotridec-11-en-2-one (3d): colorless oil (203
mg, 81%); 1H NMR (400 MHz, CDCl3) δ 6.37 (dtq, J = 15.6, 6.8, 2.0
Hz, 1H), 5.60 (dqt, J = 15.6, 6.4, 1.8 Hz, 1H), 2.42 (t, J = 7.4 Hz, 2H),
2.19−2.10 (m, 2H), 2.14 (s, 3H), 1.62−1.52 (m, 2H), 1.48−1.38 (m,
2H), 1.34−1.24 (m, 8H); 13C NMR (101 MHz, CDCl3) δ 209.5,
141.0 (q, J = 6.5 Hz), 123.3 (q, J = 270.1 Hz), 118.5 (q, J = 33.2 Hz),
43.9, 31.6, 30.0, 29.4, 29.34, 29.29, 29.1, 28.1, 24.0; 19F NMR (377
MHz, CDCl3) δ −63.89; IR (neat): νmax = 2932, 2858, 1718, 1119
cm−1; HRMS (FAB) calcd for C13H22F3O 251.1623, found 251.1620;
Rf 0.43 (hex/EtOAc, 8/1).
Hz), 40.2; 19F NMR (377 MHz, CDCl3) δ −64.32; IR (neat) νmax
=
3327, 3074, 1640, 1550, 1326, 1116 cm−1; HRMS (EI) calcd for
C11H9ClF3NO 263.0325, found 263.0328; Rf 0.40 (hex/EtOAc, 2/1).
(E)-tert-Butyldimethyl((7,7,7-trifluorohept-5-en-1-yl)oxy)silane
(3k): colorless oil (251 mg, 89%); 1H NMR (400 MHz, CDCl3) δ 6.39
(dtq, J = 16.0, 6.8, 1.8 Hz, 1H), 5.61 (dqt, J = 16.0, 6.4, 1.6 Hz, 1H),
3.62 (t, J = 6.0 Hz, 2H), 2.24−2.14 (m, 2H), 1.58−1.46 (m, 4H), 0.89
(s, 9H), 0.05 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 140.8 (q, J =
6.6 Hz), 123.3 (q, J = 269.9 Hz), 118.7 (q, J = 33.3 Hz), 62.9, 32.3,
31.4, 26.2, 24.6, 18.6, −5.1; 19F NMR (377 MHz, CDCl3) δ −62.92;
IR (neat) νmax = 2932, 2860, 1682, 1257, 1123 cm−1; HRMS (FAB)
calcd for C13H26F3OSi 283.1705, found 283.1702.
(E)-7,7,7-Trifluorohept-5-en-1-yl benzenesulfonate (3l): colorless
1
oil (278 mg, 90%); H NMR (400 MHz, CDCl3) δ 7.92−7.53 (m,
5H), 6.28 (dtq, J = 16.0, 6.8, 2.2 Hz, 1H), 5.56 (dqt, J = 16.0, 6.4, 1.6
Hz, 1H), 4.06 (t, 6.4 Hz, 2H), 2.16−2.07 (m, 2H), 1.71−1.62 (m,
2H), 1.52−1.42 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 139.8 (q, J
= 6.5 Hz), 136.2, 134.0, 129.5, 128.0, 123.1 (q, J = 270.2 Hz), 119.2
(q, J = 33.5 Hz), 70.4, 30.8, 28.3, 24.0; 19F NMR (377 MHz, CDCl3) δ
−64.59; IR (neat) νmax = 2940, 1680, 1361, 1188, 1097 cm−1; HRMS
(EI) calcd for C13H15F3O3S 308.0694, found 308.0698; Rf 0.40 (hex/
EtOAc, 4/1).
(E)-7,7,7-Trifluorohept-5-en-1-yl octanoate (3e): colorless oil (236
mg, 80%); 1H NMR (400 MHz, CDCl3) δ 6.35 (dtq, J = 15.6, 6.8, 2.0
Hz, 1H), 5.61 (dqt, J = 15.6, 6.4, 1.2 Hz, 1H), 4.06 (t, J = 6.4 Hz, 2H),
2.28 (t, J = 7.6 Hz, 2H), 2.22−2.13 (m, 2H), 1.68−1.55 (m, 4H),
1.55−1.46 (m, 2H), 1.34−1.20 (m, 8H), 0.86 (t, J = 6.8 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ 174.1, 140.2 (q, J = 6.6 Hz), 123.2 (q, J =
269.9 Hz), 119.0 (q, J = 33.5 Hz), 63.9, 34.5, 31.9, 31.2, 29.3, 29.1,
D
dx.doi.org/10.1021/jo3022346 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(E)-4-((4,4,4-Trifluorobut-2-en-1-yl)oxy)butan-1-ol (3m): colorless
oil (167 mg, 84%); 1H NMR (400 MHz, CDCl3) δ 6.40 (dtq, J = 15.8,
4.0, 2.0 Hz, 1H), 5.89 (dqt, J = 15.8, 6.8, 1.8 Hz, 1H), 4.11−4.05 (m,
2H), 3.65 (t, J = 6.0 Hz, 2H), 3.51 (t, J = 6.0 Hz, 2H), 2.03 (bs, 1H),
1.74−1.61 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 136.8 (q, J = 6.5
Hz), 123.3 (q, J = 270.1 Hz), 118.8 (q, J = 34.2 Hz), 71.3, 68.7, 62.8,
Chem. 2011, 76, 1174. (d) Shimizu, R.; Egami, H.; Hamashima, Y.;
Sodeoka, M. Angew. Chem., Int. Ed. 2012, 51, 4577.
(4) For some examples of Pd-mediated trifluoromethylation, see:
(a) Grushin, V. V.; Marshall, W. J. J. Am. Chem. Soc. 2006, 128, 12644.
(b) Wang, X.; Truesdale, L.; Yu, J. Q. J. Am. Chem. Soc. 2010, 132,
3648. (c) Cho, E. J.; Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson, D.
A.; Buchwald, S. L. Science 2010, 328, 1679. (d) Ball, N. D.; Kampf, N.
J. W.; Sanford, M. S. J. Am. Chem. Soc. 2010, 132, 2878.
(5) (a) Liu, T.; Shen, Q. Org. Lett. 2011, 13, 2342. (b) Cho, E. J.;
Buchwald, S. L. Org. Lett. 2011, 13, 6552. (c) Parsons, A. T.; Senecal,
T. D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2012, 51, 2947. (d) He,
Z.; Luo, T.; Hu, M.; Cao, Y.; Hu, J. Angew. Chem., Int. Ed. 2012, 51,
3944.
(6) For reviews on visible light photoredox catalysis, see: (a) Zeitler,
K. Angew. Chem., Int. Ed. 2009, 48, 9785. (b) Yoon, T. P.; Ischay, M.
A.; Du, J. Nat. Chem. 2010, 2, 527. (c) Narayanam, J. M. R.;
Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102.
(7) For some examples of visible light photocatalysis, see: (a) Ischay,
M. A.; Anzovino, M. E.; Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2008,
130, 12886. (b) Nicewicz, D. A.; MacMillan, D. W. C. Science 2008,
322, 77. (c) Nagib, D. A.; Scott, M. E.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2009, 131, 10875. (d) Narayanam, J. M. R.; Tucker, J. W.;
Stephenson, C. R. J. J. Am. Chem. Soc. 2009, 131, 8756. (e) Ischay, M.
A.; Lu, Z.; Yoon, T. P. J. Am. Chem. Soc. 2010, 132, 8572. (f) Andrews,
R. S.; Becker, J. J.; Gagne, M. R. Angew. Chem., Int. Ed. 2010, 49, 7274.
29.9, 26.5; 19F NMR (377 MHz, CDCl3) δ −64.28; IR (neat) νmax
=
3384, 2871, 1687, 1312, 1120 cm−1; HRMS (FAB) calcd for
C8H14F3O2 199.0946, found 199.0945; Rf 0.30 (hex/EtOAc, 2/1).
(E)-(5,5,5-Trifluoropent-3-en-1-yl)benzene (3n): colorless oil (180
1
mg, 90%); H NMR (400 MHz, CDCl3) δ 7.38−7.17 (m, 5H), 6.44
(dtq, J = 15.6, 6.8, 2.0 Hz, 1H), 5.65 (dqt, J = 15.6, 6.4, 1.2 Hz, 1H),
2.78 (t, J = 7.8 Hz, 2H), 2.54−2.44 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 142.1, 139.9 (q, J = 6.5 Hz), 128.7, 128.6, 126.5, 123.3 (q, J
= 270.3 Hz), 119.2 (q, J = 33.5 Hz), 34.5, 33.8; 19F NMR (377 MHz,
CDCl3) δ −62.40; IR (neat) νmax = 2930, 1681, 1604, 1328, 1277,
1123 cm−1; HRMS (EI) Calcd for C11H11F3 200.0813, Found
200.0814; Rf 0.75 (only hexanes).
(E)-(4,4,4-trifluorobut-1-en-1-yl)benzene (4p). colorless oil (164
1
mg, 88%); H NMR (400 MHz, CDCl3) δ 8.35−7.40 (m, 5H), 6.60
(d, J = 16.0 Hz, 1H), 6.10 (dt, J = 16.0, 7.2 Hz, 1H), 3.04−2.93 (m,
2H); 13C NMR (101 MHz, CDCl3) δ 136.9, 136.4, 128.9, 128.3,
126.7, 126.1 (q, J = 277.8 Hz), 117.4 (q, J = 3.5 Hz), 37.9 (q, J = 29.3
Hz); 19F NMR (377 MHz, CDCl3) δ −66.21; IR (neat) νmax = 2930,
1369, 1251, 1138 cm−1; HRMS (EI) calcd for C10H9F3 186.0656,
found 186.0654; Rf 0.53 (only hexanes).
(g) Neumann, M.; Fuldner, S.; Konig, B.; Zeitler, K. Angew. Chem., Int.
̈
̈
4-(Propan-2-ylidene)-1-(2,2,2-trifluoroethyl)cyclohex-1-ene (6):
Ed. 2011, 50, 951. (h) Dai, C.; Narayanam, J. M. R.; Stephenson, C. R.
J. Nat. Chem. 2011, 3, 140. (i) Nagib, D. A.; MacMillan, D. W. C.
Nature 2011, 480, 224. (j) Pham, P. V.; Nagib, D. A.; MacMillan, D.
W. C. Angew. Chem., Int. Ed. 2011, 50, 6119.
1
colorless oil (174 mg, 85%); H NMR (400 MHz, CDCl3) δ 5.66
(s, 1H), 2.81 (m, 2H), 2.73 (q, J = 11.2 Hz, 2H), 2.33(t, J = 2.4 Hz,
2H), 2.12 (m, 2H), 1.70 (s, 3H), 1.66 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 129.0, 128.0 (q, J = 2.63 Hz), 126.5 (q, J = 278.66 Hz), 42.0
(q, J = 28.79 Hz), 30.2, 29.9, 26.6, 20.4, 20.0; 19F NMR (377 MHz,
CDCl3) δ −63.44; IR (neat) νmax = 2979, 2928, 1357, 1253, 1132
cm−1; HRMS (EI) calcd for C11H15F3 204.1126, found 204.1128; Rf
0.83 (only hexanes).
(8) (a) Davies, T.; Haszeldine, R. N.; Tipping, A. E. J. Chem. Soc.,
Perkin Trans. 1 1980, 927. (b) Kamigata, N.; Fukushima, T.; Yoshida,
M. J. Chem. Soc., Chem. Commun. 1989, 1559.
(9) (a) Nguyen, J. D.; Tucker, J. W.; Konieczynska, M. D.;
Stephenson, C. R. J. J. Am. Chem. Soc. 2011, 133, 4160. (b) Wallentin,
C. J.; Nguyen, J. D.; Finkbeiner, P.; Stephenson, C. R. J. J. Am. Chem.
Soc. 2012, 134, 8875.
(10) Iqbal, N.; Choi, S. K.; Ko, E. A.; Cho, E. J. Tetrahedron Lett.
2012, 53, 2005.
(11) The Stephenson group presented an example of basic workup of
the trifluoroalkyl iodide after the reaction using 3 equiv of DBU with
refluxing in toluene; see ref 9a.
ASSOCIATED CONTENT
* Supporting Information
Characterization and spectral data of compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: echo@hanyang.ac.kr.
■
(12) pKa of Ha is in the range of 22−26; see: Butin, K. P.; Kashin, A.
N.; Beletskaya, I. P.; German, L. S.; Polishchuk, V. R. J. Organomet.
Chem. 1970, 25, 11.
(13) Allyl trifluoromethylations: (a) Parsons, A. T.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2011, 50, 9120. (b) Xu, J.; Fu, Y.; Luo, D.-F.;
Jiang, Y.-Y.; Xiao, B.; Liu, Z.-J.; Gong, T.-J.; Liu, L. J. Am. Chem. Soc.
2011, 133, 15300. (c) Wang, X.; Ye, Y.; Zhang, S.; Feng, J.; Xu, Y.;
Zhang, Y.; Wang., J. J. Am. Chem. Soc. 2011, 133, 16410. (d) Chu, L.;
Qing, F.-L. Org. Lett. 2012, 14, 2106. (e) Yasu, Y.; Koike, T.; Akita, M.
Angew. Chem., Int. Ed. 2012, 51, 9567.
(14) (a) Tokel-Takvoryan, N. E.; Hemingway, R. E.; Bard, A. J. J. Am.
Chem. Soc. 1973, 95, 6582. (b) Bonesi, S. M.; Erra-Balsells, R. J. Chem.
Soc., Perkin Trans. 2 2000, 1583.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Research Foundation
of Korea (NRF) under Grant No. NRF-2011-0013118. We
thank Prof. Daesung Lee (University of Illinois at Chicago) for
help with this manuscript.
(15) Aromatic systems can undergo trifluoromethylation via visible
light photoredox catalysis with an iridium catalyst; see ref 7i.
(16) Reactions of 1o, 7a, and 7b were conducted in CD3CN. The
given yields were detemined by 19F NMR spectroscopy. The isomeric
ratio of products from the reaction of 7a and 7b was determined by 1H
NMR and 19F NMR spectroscopy.
(17) Pathways a and b might be possible on the basis of a set of
control experiments of some alkyl halides conducted by the
Stephenson group; see ref 9b.
REFERENCES
■
(1) (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
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E
dx.doi.org/10.1021/jo3022346 | J. Org. Chem. XXXX, XXX, XXX−XXX