Copper-mediated trifluoromethylation of α-diazo esters with TMSCF3: The important role of water as a promoter

Article abstract of DOI:10.1021/ja307058c

Copper-mediated trifluoromethylation of α-diazo esters with TMSCF₃ reagent has been developed as a new method to prepare α-trifluoromethyl esters. This trifluoromethylation reaction represents the first example of fluoroalkylation of a non-fluorinated carbene precursor. Water plays an important role in promoting the reaction by activating the "CuCF₃" species prepared from CuI/TMSCF₃/CsF (1.0:1.1:1.1). The scope of this trifluoromethylation reaction is broad, and its efficiency is demonstrated in the synthesis of a variety of aryl-, benzyl-, and alkyl-substituted 3,3,3-trifluoropropanoates.

Full text of DOI:10.1021/ja307058c

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Communication
Copper-Mediated Trifluoromethylation of #-Diazo Esters
with TMSCF3: The Important Role of Water as a Promoter
Mingyou Hu, Chuanfa Ni, and Jinbo Hu
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja307058c • Publication Date (Web): 22 Aug 2012
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Journal of the American Chemical Society
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Copper-Mediated Trifluoromethylation of α-Diazo Esters with
TMSCF3: The Important Role of Water as a Promoter
5
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Mingyou Hu, Chuanfa Ni, and Jinbo Hu*
7
8
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Ling-Ling Road, Shanghai 200032, China
9
Supporting Information Placeholder
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available examples in the latter case using diazo compounds as
ABSTRACT: A copper-mediated trifluoromethylation of
α-diazo esters with TMSCF3 reagent has been developed,
which serves as a new method for the preparation of
carbene sources include copper-catalyzed polymerization of
diazoalkenes,10a the stoichiometric reaction between
pentafluorophenylcopper
and
diazoacetate,10b
and
α-trifluoromethyl esters. This trifluoromethylation reaction
represents the first example of fluoroalkylation of
copper-catalyzed reactions between alkynes (or heteroarenes)
a
and N-tosylhydrazones (precursors for diazo compounds).10c-e
non-fluorinated carbene precursor. It was found that water
plays an important role in promoting the reaction by activating
the “CuCF3” species prepared from CuI/TMSCF3/CsF
(1:1.1:1.1). The scope of this trifluoromethylation reaction is
broad, and the efficiency of the reaction is demonstrated in the
synthesis of a variety of aryl-, benzyl-, and alkyl-substituted
3,3,3-trifluoropropanoates.
Moreover,
Burton
and
co-workers
reported
the
CF2-homologation reactions of perfluorinated organocoppers
(RfCu) using trifluoromethylcopper species (“CuCF3”) as the
difluorocarbene source,11 which was believed to proceed
through the insertion of difluoromethylene into the Rf–Cu
bond.11b However, to the best of our knowledge, there has
been no report on the insertion of a non-fluorinated carbene
into a RfCu bond. Considering that diazo compounds have
been widely used as the carbene precursors,12 we envisioned
that copper-mediated (or catalyzed) cross-coupling of α-diazo
esters and Ruppert-Prakash reagent (TMSCF3)13 could result
in a facile formation of α-trifluoromethyl esters. Since various
α-diazo esters can be easily prepared by diazo-transfer reaction
of the corresponding esters,12 the overall process is the
equivalent to the trifluoromethylation of α-CH bond of an
ester with TMSCF3 reagent (eq. 2).
Trifluoromethylated compounds have attracted increasing
attention in pharmaceutical and agrochemical research because
of the unique role of CF3 group in the enhancement of the
bioactivity of organic molecules.1 Among various
transition-metal-assisted methods for the incorporation of CF3
group(s) into arenes or alkenes,2 the copper-mediated
trifluoromethylation is most extensively studied due to the
high efficiency of the reaction and the relatively low cost of
copper.2c
And
importantly,
the
copper-involved
trifluoromethylation of aryl or vinyl halides often proceeds
smoothly in the absence of an exogenous ligand.3 On the other
hand, the copper-based trifluoromethylation of sp3 carbon
atoms is much less explored,4-7 among which, most work focus
on the construction of CF3-bearing secondary or tertiary
carbon centers via allylic or benzylic trifluoromethylation
Scheme 1. Speculated Copper-Catalyzed
Trifluoromethylation of α-Diazo Esters with TMSCF3
R1
TMSCF3/F
N2
Cu CF3
R1
CO2R2
R2O2C
CuX
F3C
H
F3C Cu
R1
CO2R2
reactions,4,5
with
only
very
few
examples
of
R1
CO2R2
H-X
α-trifluoromethylation of ketones and aldehydes being
available.6 To date, a general method for the introduction of
CF3 group(s) into the α-position of aliphatic carboxylic esters
is conspicuously missing.7, 8
Initially, we speculated that “CuCF3” generated from
TMSCF3 and a Cu(I) salt could react with α-diazo esters
leading to the formation of a trifluoromethyl copper carbene
species, which would undergo CF3-migratory insertion and
subsequent protonation to afford α-trifluoromethyl esters
(Scheme 1). However, the attempted reaction between α-diazo
ester 1a and TMSCF3 with a catalytic amount of copper(I) salt
in the presences of a proton source (to regenerate the copper
catalyst) failed due to the quick formation of undesired CF3H.
Realizing that the pre-generated “CuCF3” could be used as a
R1
R2
R3
R2
R3
R1
M
M
(1)
(M = Pd, Cu, etc.)
H
N2
diazolation
Ref. 12
CF3
CO2R2
CuX/TMSCF3/F
(2)
R1
CO2R2
R1
CO2R2
R1
this work

relatively stable “CF3 ” reservoir,2c we focused on the
Transition metal carbene species possess remarkably
versatile reactivity and have been widely used in organic
synthesis for the construction of structurally diverse
molecules.9 Among many unique transformations based on
these metal carbene species, the migratory insertion of a
carbene ligand into a transition metalcarbon bond is a useful
tool for the construction of a functionalized anionic carbon
center for further transformations (eq. 1).9a,e Although carbene
insertion into palladiumcarbon bonds has been exploited for
various cross-coupling reactions,9a,e carbene insertion into
copper–carbon bonds has received less attention.10,11 The
trifluoromethylation of 1a using a stoichiometric amount of
copper salt and TMSCF3. However, when 1a was added to the
pre-generated “CuCF3” (from CuI, TMSCF3 and CsF), only a
trace amount of product 2a was detected after acidic workup
(Table 1, entry 1). Considering that CsI was formed during the
preparation of “CuCF3”, the coordination of iodide ion (I) to
copper may retard the reaction between “CuCF3” and 1a.14
Furthermore, we found that the addition of another portion of
CuI after 1a could significantly promote the reaction and the
yield of 2a increased to 77% when 1.2 equiv of CuI was used
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Table 1. Screening of the Reaction Conditionsa
and 1a at room temperature, to our delight, the reaction
1
2
3
4
5
6
7
8
proceeded smoothly to give 2a in excellent yield with good
reproducibility (Table 1, entry 7). It is much impressive that
water itself could promote the reaction and 2a was obtained in
31% yield when 1.0 equiv of water was added (Table 1, entry
8). When less than 10 equiv of water was used, there was no
substantial improvement of the yield (Table 1, entry 9).
Notably, when the amount of water was increased to 20 equiv,
the yield was strikingly improved to 69% (Table 1, entry 10).
Further optimization indicated that the use of 44 equiv of
water at room temperature gave the best result (Table 1,
entries 1114). As for the amount of copper reagent, “CuCF3”
prepared from 1.5 equiv of CuI gave better results than those
with 1.2 equiv or less, and more excessive amount of CuI
could not further improve the yield significantly (Table 1,
entries 1516). Among several protic additives that were
tested, tBuOH, EtOH, MeOH, and PhOH were found to be
inferior to water (Table 1, entries 1720).
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Table 2. Trifluoromethylation of Various -Diazo Estersa
1) CuI (1.5 equiv), TMSCF3 (1.65 equiv),
N2
CF3
R1 CO2R2
CsF (1.65 equiv), NMP, RT, 30 min
R1
CO2R2
2) 1 (1 equiv) in NMP, H2O (44 equiv),
rt, 20 h
1
2
CF3
CO2Et
CF3
CO2Et
CF3
CO2Et
CF3
CO2Et
R
EtO
2a, 82%
(5 mmol scale: 84%)
2b, 75%
2c, R = 2-Me, 85%
2d, R = 4-Me, 88%
2e, 94%
(5 mmol scale: 90%)
CF3
CF3
CO2R2
CF3
CF3
MeO
MeO
(Table 1, entries 25). When NMP (1-methylpyrrolidin-2-one)
was used instead of DMF as solvent, a higher yield (88%) of
2a was obtained (Table 1, entry 6). It is interesting that when
CO2Et
CO2Et
CO2Et
R
MeO
F
2g, R2 = Me, 96%
2h, R2 = Et, 87%
2f, 92%
2j, 82%
2k, R = 2-Br, 79%
2l, R = 4-Br, 75%b
2i,
Cl
Cl
R
2 = iPr, 91%
the reaction was performed in
a
sealed tube,
CF3
CO2Et
CF3
CF3
CO2Et
CF3
gem-difluoroolefin 4a was formed as the major product and 2a
as the minor product (Scheme 2). Furthermore, prolonged
reaction time did not significantly increase the yield of 2a after
the initial 20 minutes (Scheme 2), which demonstrates that 2a
resulted from the quenching of the labile copper intermediate
O
R1
CO2Et
R
O
O2N
2q, 0 (81%)c
R1 = 4-MeOC6H4,
2m, R = 2-Cl, 73%
2n, R = 3-Cl, 70%
2o, R = 4-Cl, 78%
2p, 66%
2r, 88%
CF3
CO2Et
Me
R
CF3
CF3
CO2Et
CF3
3a by
a random proton source (most probably from
CO2Et
R
CO2Et
2t, 69%d
2s, 81%
2u, R = H, 78%
2v, R = Me, 70%
2w, R = OMe, 59%
2x, R = tBu, 72%
adventitious water in the reaction system) (Table 1, entries
16). When the amount of proton source was insufficient,
β-elimination of fluoride from 3a would lead to difluoroolefin
4a.
Cl
CF3
Br
CF3
CF3
CF3
CO2Et
R
R
CO2Et
CO2Et
nC8H17
CO2Et
Cl
2y, 55% (80%)e
2za, 80%d
2zb, R = Cl, 87%
2zc, R = OMe, 84%
2zd, 92%
Scheme 2. Formation of Difluoroolefina
a Unless otherwise noted, reactions were performed on 0.5 mmol scale by adding 1a and
water into the pre-generated "CuCF3". Yields refer to isolated yields of the analytically pure
products. b The reaction was performed at 35 oC. c The yield of the reaction performed on
0.2 mmol scale at 60 oC using "CuCF3" (2.0 equiv) as trifluoromethylation reagent, CuI (1.2
equiv) and H2O (1 equiv) as additives was given in the parenthesis. d The reaction was
performed at 40 oC. e The number in the parenthesis refers to 19F NMR yield with PhCF3 as
an internal standard.
Having identified the optimal reaction conditions (Table 1,
entry 13), we further examined the scope of this
trifluoromethylation reaction (Table 2). Generally, both aryl-,
benzyl- and other alkyl-substituted α-diazo esters reacted
smoothly to give α-trifluoromethyl esters 2 in moderate to
excellent yields, and no aromatic trifluoromethylation
occurred in the cases of haloaryl-substituted α-diazo esters
(2j2p and 2y2zb). Moreover, the reaction also tolerates
C=C bonds and no intramolecular cyclopropanation product
was detected in the case of 2r. The aryl α-diazo esters with
electron-donating substituent such as methyl, methoxy and
ethoxy groups on the aromatic ring gave α-trifluoromethyl
esters 2 in excellent yields (2c2i), while those with weak
Next, we examined the influence of protic additives on the
reaction. Although it has been known that long-chain
perfluoroalkylcoppers are not so sensitive towards water,3a the
similar data for trifluoromethylcopper species are not available.
Indeed, we found that “CuCF3” (prepared from
CuI/TMSCF3/CsF, in a ratio of 1:1.1:1.1) in NMP (1.0 M) in
the presence of 66 equiv of water was hardly transformed into
CF3H at low temperatures, and only ~5% of “CuCF3” was
decomposed at room temperature in 5 hours (see section 6.1 in
Supporting Information). When 1.0 equiv of water and 1.2
equiv of CuI were added into the reaction mixture of “CuCF3”
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electron-withdrawing substituent such as Cl and Br at the
aromatic rings gave slightly decreased yields (2k2p).
However, the α-diazo ester 1q with strong
addition to the species 7) (Figure 1, C), and the consumption
1
2
3
4
5
6
7
8
of 8a is much slower than its formation (Figure 1, C and D).
Moreover, the N2 evolution experiment showed that the
decomposition of diazo compound 1a was a slow process (see
section 6.4 in Supporting Information). Based on these results,
the species 8a was tentatively identified as the complex
CuCF3•1a rather than a carbene-ligated trifluoromethylcopper
species 9.17
Although it is difficult to identify the reactive intermediate
with 19F NMR spectroscopy when the reaction was performed
in the presence of water (only two trifluoromethylcopper
species assigned as 5 and 6 were observed, see section 6.1 in
Supporting Information), we conjecture that water serves as
the “scavenger” of iodide ion (by the formation of hydrated
iodide ion)18 to promote the ligand exchange of copper
complexes affording the reactive species 8 (see Scheme 3) at a
low concentration. If water is used in a relatively small
amount (less than 10 equiv), the saturation of the mixed
solvent by iodide ion makes the formation of 8 (and the
subsequent trifluoromethylation) less efficient. The
assumption of water-promoted iodide complex dissociation
was further supported by our observation that the yield of 2a
decreased significantly with the addition of external KI into
the reaction mixture (see section 6.5 in Supporting
Information).
a
electron-withdrawing substituent (NO2) is unreactive under the
optimized conditions. Note that this reaction was not sensitive
to the steric bulkiness of the ester group adjacent to the
carbenoid carbon, and changing from the methyl, ethyl, to
isopropyl esters caused no significant drop of yield (2g2i).
For the benzyl-substituted α-diazo esters (2s2za), the yields
were generally lower than the normal alkyl-substituted ones
(2zb2zd), probably due to the occurrence of the competitive
1,2-H shift of the copper carbene intermediates. For example,
in the case of 1y, besides the desired product 2y, (E)-ethyl
3-(2,4-dichlorophenyl)acrylate was also detected as the
byproduct (6% by GC-MS). α-Trifluoromethyl carboxylic
esters are key intermediates for the synthesis of non-ester
pyrethroids insecticides such as flufenprox15a (for its concise
synthesis from 2e, see sections 5.1–5.3 in Supporting
Information) and fluorinated analogues of non-steroidal
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anti-inflammatory drugs15b
.
Scheme 3. Proposed Mechanism
TMSCF3/F
CuI
+
(3)
(4)
[Cu(CF3)I]
1/2[Cu(CF3)2]
1/2[CuI2]
NMP
5
6
N2
H O
2
NMP /
+
CuCF3
1
+
[Cu(CF3)I]
I
aq
R1
CO2R2
+
1
1
5
8
NMP / H2O
[CuI2]
N2
+
(5)
CuI
1
I
aq
10
R1
R1
F3C Cu
Figure 1. Monitoring of the CuI-promoted trifluoromethylation of
α-diazo ester 1a with 19F NMR spectroscopy at rt (the chemical
shifts were determined relative to PhCF3 at –63.0 ppm). (A)
“CuCF3” prepared from CuI, TMSCF3 and CsF in 1:1.1:1.1 ratio;
(B) 5 min after the addition of 2/3 equiv of CuI into sample A; (C)
10 min and (D) 60 min after the addition of 2/3 equiv of CuI and
2/3 equiv of 1a into sample A.
CuCF3
1
Cu
CF3
CO2R2
8
CO2R2
9
3
CuI2
1/2 H2O
1/2 Cu2O
[Cu(CF3)I]
5
R1
CF3
CO2R2
N2
I
Cu
11
CuI
1
R1
CO2R2
10
2
Based on aforementioned results and discussion, we
propose mechanism for the current CuI-mediated,
To gain more insights into the present copper-mediated
trifluoromethylation reaction, the composition of “CuCF3” and
its reaction with 1a and additional CuI were studied with 19F
NMR spectroscopy. When CuI, TMSCF3 and CsF were mixed
in a 1:1.1:1.1 ratio in NMP, apart from the two major
trifluoromethylcopper species which were tentatively assigned
as [Cu(CF3)I]– (5, –28.7 ppm) and [Cu(CF3)2]– (6, –31.9 ppm)
according to the reported NMR data16 (neither of them is
reactive towards 1a under this condition), a new species 7 at
–26.9 ppm was also observed in small amount (Figure 1, A);
and the species 7 became predominant when 2/3 more equiv of
CuI was added into the mixture (Figure 1, B). By comparison
with the 19F NMR data (–27.2 ppm in DMF, –27.8 ppm in
a
water-promoted trifluoromethylation of 1 with TMSCF3
reagent (Scheme 3). Firstly, the reaction of CuI, TMSCF3 and
CsF (in
a
1:1.1:1.1 ratio) gives the dicoordinated
trifluoromethylcopper species 5, which is in equilibrium with
bis(trifluoromethyl)copper species 6 and [CuI2]– via ligand
redistribution on copper (eq. 3).19 After the addition of α-diazo
ester 1 and water, a small amount of reactive intermediate
complex 8 is formed from 5 by water-promoted α-diazo
esteriodide ion exchange reaction (eq. 4). The extrusion of N2
from 8 affords trifluoromethyl copper carbene species 9 and
the subsequent migration of CF3 group to the carbenic carbon
atom of 9 results in α-CF3-substituted copper species 3. The
final hydrolysis of 3 by water gives product 2 and the
unreactive Cu2O.20 Alternatively, based on the known
copper-catalyzed cyclopropanation between diazo compounds
and alkenes,21 the complex 10 generated from [CuI2]– by a
3c
NMP) of “ligandless” CuCF3 prepared from CF3H and its
reactivity with diazo ester 1a (see section 6.3 in Supporting
Information), the species 7 was tentatively assigned as
solvent-stabilized CuCF3, in which the solvent molecule NMP
acted as a ligand. It is likely that the abstraction of iodide ion
by CuI (to form [CuI2]–) promotes the formation of 7. When
1a (2/3 equiv) and CuI (2/3 equiv) were added into the
pre-generated “CuCF3”, a new peak at –26.5 ppm appeared (in
similar ligand-exchange reaction is also
a
possible
intermediate. The extrusion of N2 from 10 affords copper
carbene species 11. Both 10 and 11 can undergo ligand
redistribution reaction with 5 to give 8 and 9, respectively.
3
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see: (d) Mizuta, S.; Galicia-López, O.; Engle, K. M.; Verhoog, S.;
Wheelhouse, K.; Rassias, G.; Gouverneur, V. Chem. Eur. J. 2012, 51,
8583; and references therein.
Although we could not rule out the formation of complex 10,
11 is less likely involved in this water-promoted
trifluoromethylation reaction as we did not observe any
intramolecular cyclopropanation byproduct in the case of C=C
bond-containing α-diazo ester 1r.
1
2
3
4
(5)
For
examples
of
Cu-mediated/catalyzed
benzylic
trifluoromethylation, see: (a) Kawai, H.; Furukawa, T.; Nomura, Y.;
Tokunaga, E.; Shibata, N. Org. Lett. 2011, 13, 3596; and references
therein. (b) See Ref. 3e.
In summary, we disclosed
a mild copper-mediated
5
6
7
8
trifluoromethylation of α-diazo esters with TMSCF3 to give
α-trifluoromethyl esters, which represents the first
fluoroalkylation of a non-fluorinated carbene precursor. Water
acts as an efficient activating agent in promoting the reaction
(6) For examples on Cu-mediated/catalyzed α-trifluoromethylation
of aldehydes and ketones, see: (a) Bernard R. Langlois, Eliane
Laurent, Nathalie Roidot Tetrahedron Lett. 1992, 33, 1291. (b) Kirij,
N.V.; Pasenok, S.V.; Yagupolskii, Yu. L.; Tyrra, W.; Naumann D. J.
Fluorine Chem. 2000, 106, 217. (c) Allen, A. E.; MacMillan, D.W. C.
J. Am. Chem. Soc. 2010, 132, 4986.
(7) Very recently, a Cu-catalyzed electrophilic trifluoromethylation
of β-ketoesters for the construction of quaternary carbon centers was
reported, see: Deng, Q.-H.; Wadepohl, H.; Gade, L. H. J. Am. Chem.
Soc. 2012, 134, 10769.
9
with
trifluoromethylcopper
species
prepared
from
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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27
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CuI/TMSCF3/CsF (1:1.1:1.1). We propose that the hydration
of iodide ion facilitates the formation of the intermediate
α-diazo ester-coordinated trifluoromethylcopper 8, and then
the reaction occurs via N2-extrusion and subsequent migratory
insertion of the carbene ligand into the Cu–CF3 bond. This
reaction is applicable for α-aryl, α-benzyl, and α-alkyl diazo
esters and tolerates bromo, chloro, fluoro, ether and double
bond functionalities. Not only does our present work offer a
simple and general way to introduce CF3 group into α-position
of structurally diverse carboxylic esters, it also provides
fundamentally important insights into the reactivity of the
elusive trifluoromethylcopper species. Further investigation of
the more detailed reaction mechanism as well as the synthetic
applications of the reaction are currently underway in our
laboratory.
(8) Hagooly, A.; Rozen, S. J. Org. Chem. 2004, 69, 7241; and
references therein.
(9) (a) Dörwald F. Z. Metal Carbenes in Organic Synthesis;
Wiley-VCH: Weinheim, 1999. (b) Kirmse, W. Angew. Chem., Int. Ed.
2003, 42, 1088. (c) de Frémont, P.; Marion, N.; Nolam, S. P. Coord.
Chem. Rev. 2009, 253, 862. (d) Zhang, Y.; Wang, J. Eur. J. Org.
Chem. 2011, 1015. (e) Franssen, N. M. G.; Walters, A. J. C.; Reeka, J.
N. H.; de Bruin, B. Catal. Sci. Technol., 2011, 1, 153.
(10) (a) Imoto, M.; Nakaya, T. J. Macromol. Sci., Rev. Macromol.
Chem., 1972, 7, 1; and references therein. (b) Cairncross, A.;
Sheppard, W. A. J. Am. Chem. Soc. 1968, 90, 2186. (c) Zhao, X.; Wu,
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(12) Doyle, M. P.; Mckervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; John Wiley &
Sons: New York, 1998.
ASSOCIATED CONTENT
SUPPORTING INFORMATION
Experimental procedures and characterization for all new
compounds, including 1H, 13C, and 19F NMR spectra.
AUTHOR INFORMATION
Corresponding Author
jinbohu@sioc.ac.cn
(13) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757.
(14) For examples of ligands associating with copper to retard the
decomposition of diazo compounds, see: (a) Wulfmanb, D. S.; W.
Peace, W.; Stefeen, E. K. Chem. Commun. 1971, 1360. (b) Salomon,
R. G.; Kochi, J. K.; J. Am. Chem. Soc.1973, 93, 3300. (c)
Díaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.; Prieto, F.;
Pérez, P. J. Organometallics 1999, 18, 2601.
ACKNOWLEDGMENT
This work was supported by the National Basic Research Program
of China (2012CB821600, 2012CB215500) and the National
Natural Science Foundation of China (20825209, 20832008).
REFERENCES
(15) (a) Theodoridis, G. Fluorine-Containing Agrochemicals: An
Overview of Recent Developments in Fluorine and the Environment:
(1) (a) Fluorine in Medicinal Chemistry and Chemical Biology (Ed.:
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D. Bioorganic and Medicinal Chemistry of Fluorine, Wiley-VCH,
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(e) Hagmann,W., K. J. Med. Chem. 2008, 51, 4359. (f) Filler, R; Saha,
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(2) For recent reviews, see: (a) Furuya, T.; Kamlet, A. S.; Ritter, T.
Nature 2011, 473, 470. (b) Roy, S.; Gregg, B. T.; Gribble, G. W.; Le,
V.-D.; Roy, S. Tetrahedron 2011, 67, 2161. (c) Tomashenko, O. A.;
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(3) For examples, see: (a) McLoughlin, V. C. R.; Thrower, J.
Tetrahedron 1969, 25, 5921. (b) Urata, H.; Fuchikami, T.
Tetrahedron Lett. 1991, 32, 91. (c) Zanardi, A., Novikov, M. A.;
Martin, E.; Benet-Buchholz, J.; Grushin, V. V. J. Am. Chem. Soc.
2011, 133, 20901. (d) Novák, P; Lishchynskyi, A.; Grushin, V. V.
Angew. Chem., Int. Ed. 2012, 51, 7767. (e) Chen, Q.; Wu, S. J. Chem.
Soc., Chem. Commun. 1989, 705.
Agrochemicals, Archaeology, Green Chemistry
& Water (Ed.:
Tressaud, A.), Elsevier, Amsterdam, 2006. (b) Yamauchi, Y.; Hara, S.;
Senboku, H. Tetrahedron 2010, 66, 473.
(16) (a) Kuett, A.; Movchun, V.; Rodima, T.; et. al. J. Org. Chem.
2008, 73, 2607. (b) Dubinina, G. G.; Ogikubo, J.; Vicic, D. A.
Organometallics 2008, 27, 6233. (c) For a discussion on the 19F NMR
chemical shift difference of [Cu(CF3)I]– in our cases, see section 6.2
in Supporting Information.
(17) For an example of well-defined α-carbonyl diazoalkane
complex of copper(I), see: Straub, B. F.; Rominger, F.; Hofmann, P.
Organometallics 2000, 19, 4305.
(18) For water-promoted dissociation of [CuI2]–, see: Kauffman, G.
B.; Fang, L. Y. Inorg. Synth. 1983, 22, 101.
(19) According to the overall yield (70–80%) of the “CuCF3”
species, the solution maybe also contain some other copper species
such as CuI, which can promote the trifluoromethylation. However, as
shown in Table 1, entries 1-4, its contribution to the final yield is
limited because it may transform into the unreactive species such as
[CuI2]– in the absence of water.
(20) CuOH is a very elusive species due to its instability, and the
theoretical study shows that it readily decomposes into stable
substances Cu2O and H2O. (See: Korzhavyi, P. A.; Soroka I. L.; Isaev,
(4)
For
examples
of
Cu-mediated/catalyzed
allylic
trifluoromethylation, see: (a) Andrew T. Parsons and Stephen L.
Buchwald, Angew. Chem., Int. Ed. 2011, 50, 9120. (b) Chu, L.; Qing,
F.-L. Org. Lett. 2012, 14, 2106. (c) See Ref. 3e. For more examples,
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E. I.; Lijia, C.; Johansson, B. Proc. Natl. Acad. Sci. USA. 2012, 109,
686). In our case, red precipitate (that is assumed to be Cu2O) was
observed after the completion of the reaction. We also tried the
trifluoromethylation of 1a with “CuCF3” using Cu2O instead of CuI as
the additive, and only a trace amount of product 2a was detected.
(21) (a) Salomon, R. G.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95,
3300. (b) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B.
Chem. Rev. 2003, 103, 977.
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CF
CuI/TMS 3/CsF (1:1.1:1.1)
N2
F3C H
Ph
CO2Et
CF
"Cu 3" (1.5 equiv)
H2O (x equiv)
Ph
CO2Et
NMP, rt
x =1, 31% yield (65 h)
x =44, 83% yield (20 h)
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