Trifluoromethylation of arenediazonium salts with fluoroform-derived CuCF3 in aqueous media

Article abstract of DOI:10.1039/c4cc04930f

A new protocol has been developed for trifluoromethylation of arenediazonium salts with moisture-sensitive CuCF₃ (from fluoroform) in aqueous media. The reaction is governed by a radical mechanism, tolerates a broad variety of functional groups, and is applicable to the synthesis of complex, polyfunctionalized molecules. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc04930f

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Trifluoromethylation of arenediazonium salts with
fluoroform-derived CuCF in aqueous media†
3
Cite this: Chem. Commun., 2014,
0, 10237
5
a
b
a
Anton Lishchynskyi, Guillaume Berthon and Vladimir V. Grushin*
Received 27th June 2014,
Accepted 11th July 2014
DOI: 10.1039/c4cc04930f
www.rsc.org/chemcomm
A new protocol has been developed for trifluoromethylation of arene-
diazonium salts with moisture-sensitive CuCF (from fluoroform) in
3
aqueous media. The reaction is governed by a radical mechanism,
tolerates a broad variety of functional groups, and is applicable to the
synthesis of complex, polyfunctionalized molecules.
7–9
Scheme 1 Trifluoromethylation of arenediazonium compounds.
Trifluoromethylated aromatic compounds are in increasingly high
demand for the synthesis of agrochemicals, pharmaceuticals, and Indeed, readily available and inexpensive aromatic amines are highly
1
specialty materials. The currently employed old technology to attractive starting materials, and the dye industry has proven the
11
manufacture benzotrifluorides is based on the Swarts Cl/F exchange feasibility of safely handling diazonium compounds on a large
1
2
reaction of HF with benzotrichlorides, which, in turn, are produced scale. However, the currently available Sandmeyer trifluoro-
2
via exhaustive chlorination of the CH
two-step process has exceedingly low functional group tolerance and operations due to two main reasons. First, the CF
3
group on the ring. As this methylation methods are not viable for larger scale, safe
reagents
is environmentally hazardous, considerable effort has been made employed in the reaction are cost-prohibitive. Second, all three
3
7–9
7
–9
toward the development of alternative ways to introduce the CF
3
Sandmeyer trifluoromethylation protocols
group into the desired position of the aromatic ring. The most sensitive CF reagents and therefore require anhydrous conditions.
common substrates for aromatic trifluoromethylation are aryl An attempt to trifluoromethylate an arenediazonium salt with CuCF
employ moisture-
3–6
3
3
9
3
,4
5
halides and, more recently, aryl boronic acids. Last year, three in water as a co-solvent gave the desired product in 10% yield.
groups reported their innovative developments of the previously Aqueous conditions, however, are frequently a critical safety require-
unknown Sandmeyer-type trifluoromethylation of arenediazonium ment for a process involving diazonium salts. Furthermore, water is
salts (Scheme 1). Fu et al. used Umemoto’s reagent with the Cu overall by far the best solvent for the synthesis and many reactions
in situ using of arenediazonium salts in terms of not only safety, but also
3 2
powder (3 equiv.) as the CF source and generated ArN
i-AmONO in MeCN. Gooßen and co-workers treated pre-isolated efficiency, cost, operational simplicity, and ecology.
We reasoned that the cost problem could be addressed by
from the direct cupration of fluoroform (Scheme 2),
EtCN to trifluoromethylate ArN2 Cl produced from the corre- recently discovered in our laboratories at ICIQ.
7–9
7
+
11a
8
+
À
ArN
2
BF
4
with CuCF
3
generated from CuSCN, CF
3
SiMe
3
, and
9
Cs CO in MeCN. Wang’s group employed AgCF (3.5 equiv.) in using CuCF
2
3
3
3
+
À
13,14
As a powerful
4n,5j,13,15,16
sponding aniline and t-BuONO/HCl, also in EtCN.
trifluoromethylating agent,
CuCF
3
is produced using
7–9
The Fu–Gooßen–Wang developments have been recently high- only low-cost materials and fluoroform, by far the cheapest and
10
3a,4n,5j,13–18
lighted with the right emphasis on potential industrial applicability. most readily available CF
3
source.
While being low-cost, the fluoroform-derived CuCF
3
reagent
is nonetheless moisture-sensitive. Therefore, addressing the
equally important water incompatibility problem seemed to
a
Institute of Chemical Research of Catalonia (ICIQ), Avgda. Pa ¨ı sos Catalans 16,
3007 Tarragona, Spain. E-mail: vgrushin@iciq.es; Fax: +34 977 920 825;
4
Tel: +34 977 920 200
b
Syngenta Crop Protection, M u¨ nchwilen AG, Schaffhauserstrasse, Postfach 4332,
Stein, Switzerland
†
Electronic supplementary information (ESI) available: Full details of synthetic,
mechanistic (PDF), and crystallographic (CIF) studies. CCDC 993889–993892. For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c4cc04930f
13
3
Scheme 2 Direct synthesis of CuCF from fluoroform.
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be impossible. Herein we report, however, that against all expecta- Table 1 Trifluoromethylation of arenediazonium salts with fluoroform-
7–9
derived CuCF3 under aqueous conditions
tions and reported data, aqueous media can be most successfully
employed for high-yielding trifluoromethylation reactions of arene-
diazonium compounds with fluoroform-derived CuCF3.
Two main stages of studies involving numerous exploratory
and optimization experiments preceded the key novel findings.
These two stages are succinctly summarized below; full details
are given in the ESI.†
First, we looked into trifluoromethylation of preisolated
+
À
4-XC
6
H
4
N
2
BF
4
2 3
(X = MeO, Br, NO ) with CuCF (1.1 equiv.)
1
3
prepared from CHF in DMF and stabilized with Et NÁ3HF.
3
3
These reactions gave mainly the reduction product XC H and the
6
5
yields of the desired trifluoromethylated derivatives 4-XC H CF were
6
4
3
only 8–17%. It was then found that the reduction could be largely
suppressed and the yield of the desired product improved dramati-
cally by using MeCN as a co-solvent. In this way, 4-MeOC H CF was
6 4 3
produced in 73% yield along with only small quantities (ca. 5–7%) of
anisole. Co-solvents other than MeCN (EtCN, PrCN, t-BuCN, PhCN,
(
CF ) CHOH, CF CH OH, t-BuOH, Me CO, and HCONH ) were also
3 2 3 2 2 2
examined but were found to be less efficient.
In the second stage, we explored the possibility of trifluoro-
+
2
À
methylation of ArN
X
generated in situ from the corresponding
aniline. Initially, CuCF
3
in DMF was added to a freshly prepared
solution of an aromatic amine and t-BuONO, in the hope that a
quick reaction of the copper reagent with the gradually produced
diazonium salt would result in more chemoselective trifluoromethyl-
ation. However, adding CuCF /DMF to just premixed 4-MeC H NH
3
6
4
2
and t-BuONO in MeCN gave 4-MeC H CF in only 30–40% yield.
6
4
3
Independent experiments showed that t-BuONO decomposes CuCF3
and so do aromatic amines, albeit more slowly. It thus became clear
that the diazonium substrate should be fully preformed prior to the
1
9
See ESI for details. Yields were determined by F NMR (0.5 mmol scale)
3
reaction with CuCF . Therefore, we optimized diazotization of
with an internal standard. Yields of isolated pure (498% by NMR)
a
ArNH (Ar = 4-MeOC
2
6
H
) with RONO (R = t-Bu, i-Am) in MeCN in products (0.75–5 mmol scale) are shown in parenthesis. 91% purity.
4
the presence of various acid promoters. The best results were
obtained with MeSO H, Et OÁBF , and HCl in dioxane, furnishing
3
2
3
+
2
À
ArN X solutions that gave ArCF in 50–60% yield upon treatment in 70–85% yield, with the undesired hydrodediazoniation
3
with CuCF . These reactions still side-produced ArH (3–10%), occurring only to a minor extent (o3–5%). In most cases, the
3
2
Ar (0–2%), ArNNAr (3–10%), and ArCl (15–40% if HCl was used). formation of side products could be minimized by adjusting
2
1
In all of the above-described reactions, rigorously anhydrous the reagent concentration and the amount of the acid used.
conditions were maintained in order to avoid decomposition of The method is compatible with a broad variety of both electron-
moisture-sensitive CuCF . As counterintuitive and unwise as it might donating and -withdrawing functional groups, such as Me,
seem, we examined the reaction of the hydrolysable CuCF reagent MeO, NO , CONH, AcO, MeO C, HO C, I, Cl, F, CN, PhNQN,
3
3
2
2
2
19
with aqueous solutions of arenediazonium salts. To our delightful and HCRC. The trifluoromethylation of 3-aminopyridine (1l)
surprise, the reaction of CuCF in DMF with a solution of in 65% yield is a notable improvement over the highest 10%
3
+
À
9
4
-MeOC H N HSO4 prepared from p-anisidine and NaNO2/ yield reported in the literature.
6 4 2
H SO
2 4
in water produced the desired ArCF
3
product in 30–35% yield.
To demonstrate the scalability and synthetic value of the method,
Subsequent thorough optimization resulted in a high-yielding process we performed the trifluoromethylation of N-(4-aminophenyl)-
for trifluoromethylation of a broad variety of arenediazonium salts acetamide (1d), 4-aminobenzoic acid (1f), (E)-4-(phenyldiazenyl)aniline
under aqueous conditions (Table 1). While other acids (HBF
4
, HNO
3
(1g), 5-aminoisoquinoline (1w), and 1-(2-aminophenyl)ethanone
and H PO ) also appeared to be suitable for the reaction, superior (1x) on a 3–5 mmol scale and isolated the desired trifluoro-
3
4
20
results were obtained with aqueous HF, in the absence of any methylated products 2d (0.79 g; 78%), 2f (0.46 g; 80%), 2g (0.68 g;
stronger acid. Premixing a freshly generated aqueous solution of the 68%), 2w (0.68 g; 69%), and 2x (0.37 g; 65%) in pure form. The
diazonium salt with MeCN prior to the addition of CuCF benefited reactions of multi-functionalized substrates 1bb–1dd under the
3
both the yield and selectivity of the reaction.
developed conditions furnished close analogues of marketed
Using the new protocol, two thirds of the 30 substrates pesticides 2bb–2dd in 41–78% isolated yield. All of them were
explored in this work (Table 1) have been trifluoromethylated fully characterized by X-ray crystallography (Fig. 1).
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molecules from the metal center of CuCF
3
, thereby changing
not only the rate of electron transfer to the diazonium cation
but also the nature of the solvent cage. The presence of more
2
8
MeCN, a poor H atom donor for radicals, in the coordination
sphere of the metal center apparently suppresses the undesired
hydrodediazoniation side process. This effect is likely enhanced
by HF that also benefits the reaction (see above). Being a good
H-bond donor, HF binds much more strongly to DMF (b = 0.76)
2
9
than to MeCN (b = 0.40), thereby lowering the coordination
ability of DMF in further favor of the MeCN–CuCF ligation.
3
In conclusion, we have demonstrated that low-cost fluoroform-
derived CuCF can efficiently trifluoromethylate arenediazonium
3
Fig. 1 X-ray structures of 2w, 2bb, 2cc, and 2dd (clockwise from bottom
right) with all H atoms omitted for clarity.
compounds in aqueous media. Consequently, both critical require-
ments for the Sandmeyer trifluoromethylation on a larger scale in a
safe manner have been met. The trifluoromethylation reaction of
arenediazonium salts in the aqueous medium is governed by a
radical mechanism and tolerates a broad variety of functional
groups. Successful scaleups and applications of the method to
the synthesis of bioactivity-related polyfunctionalized molecules
have been demonstrated. The successful trifluoromethylation with
Scheme 3 Radical clock experiment.
moisture-sensitive, nucleophilic CuCF in the presence of water
3
under acidic conditions is remarkable. This finding is a good
Fu and Gooßen have presented evidence for a radical mecha- testimony that it is the rate constant ratio that is crucial for one
nism of the Sandmeyer-type trifluoromethylation, whereas Wang’s of two competing reactions to prevail even if both processes are
7
8
9
experiments suggest that the silver-promoted reaction is a non- ‘‘fast’’ from the perspective of conventional chemical ‘‘wisdom’’.
radical process. Numerous transformations of arenediazonium salts
We thank Drs J. Benet-Buchholz, E. C. Escudero-Ad ´a n, E. Martin,
including the classical Sandmeyer and M. Mart ´ı nez Belmonte (ICIQ) for crystallographic studies and
reaction. We probed the reaction mechanism under our condi- Drs J. Cassayre, A. J. F. Edmunds, M. El Qacemi, N. Fedou,
tions with a radical clock substrate, 2-(allyloxy)aniline 3 (k
= 5.3 Â E. Godineau, A. De Mesmaeker, M. Pouliot, A. Robinson, and
0 s at 25 1C). This reaction gave the cyclic trifluoromethylated H. Smits (Syngenta) for discussions. Syngenta AG, the ICIQ Founda-
product 4 in 77% yield (Scheme 3) and only traces (ca. 1%) of the tion, and the Spanish Government (Grant CTQ2011-25418) are
11,22
are mediated by aryl radicals,
23
c
9
À1
24
1
19
corresponding linear compound (GC-MS and F NMR).
gratefully acknowledged for support of this research.
While the radical clock experiment pointed unambiguously
2
5
to a radical mechanism, stoichiometric quantities of such
radical traps as butylated hydroxytoluene (BHT), 2,2-diphenyl-1-
picrylhydrazyl (DPPH), and 1,1-diphenylethylene appeared to
Notes and references
1
For selected monographs, see: (a) J. H. Clark, D. Wails and
T. W. Bastock, Aromatic Fluorination, CRC Press, Boca Raton, FL,
+
À
have no significant effect on the reaction of 4-MeOC
6
H
4
N
2
BF
4
1996; (b) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley, Wein-
26
with CuCF
3
.
These results along with the minor formation of
heim, 2004; (c) K. Uneyama, Organofluorine Chemistry, Blackwell,
Oxford, 2006; (d) I. Ojima, Fluorine in Medicinal Chemistry and
Chemical Biology, Wiley-Blackwell, Chichester, UK, 2006.
R. Filler, Adv. Fluorine Chem., 1970, 6, 1.
arenes in the reaction (see above) point to a radical pathway within
the solvent cage, which is often characteristic of Sandmeyer-type
2
22,23,27
reactions.
The step leading to Ar–CF
3
bond formation is
3 For recent comprehensive reviews, see: (a) O. A. Tomashenko and
V. V. Grushin, Chem. Rev., 2011, 111, 4475; (b) S. Roy, B. T. Gregg,
G. W. Gribble, V.-D. Le and S. Roy, Tetrahedron, 2011, 67, 2161;
evidently faster than the escape of the aryl radical from the solvent
cage, yet roughly two orders of magnitude slower than the corre-
sponding cyclization reaction (Scheme 3).
The main source of hydrogen in the hydrodediazoniation
side reaction is the aprotic dipolar solvent (DMF, NMP, or DMA)
(
c) A. Lishchynskyi, P. Nov ´a k and V. V. Grushin, in Science of
Synthesis: C-1 Building Blocks in Organic Synthesis 2, ed. P. W. N. M.
van Leeuwen, Thieme, Stuttgart, 2013, p. 367.
For most recent reports not covered in the review article cited in
ref. 3a, see: (a) C. P. Zhang, Z. L. Wang, Q. Y. Chen, C. T. Zhang,
Y. C. Gu and J. C. Xiao, Angew. Chem., Int. Ed., 2011, 50, 1896;
4
3
that is used in the preparation of the CuCF reagent. A detailed
(
1
b) I. Popov, S. Lindeman and O. Daugulis, J. Am. Chem. Soc., 2011,
33, 9286; (c) H. Morimoto, T. Tsubogo, N. D. Litvinas and J. F. Hartwig,
study (see the ESI†) has demonstrated that the aryl radicals
abstract H atoms from both the methyl groups and the formyl
moiety of DMF. The arene side products are formed in larger
quantities in NMP that gives rise to more stable secondary
Angew. Chem., Int. Ed., 2011, 50, 3793; (d) O. A. Tomashenko,
E. C. Escudero-Ad ´a n, M. Mart ´ı nez Belmonte and V. V. Grushin, Angew.
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( f ) Y. Li, T. Chen, H. Wang, R. Zhang, K. Jin, X. Wang and C. Duan,
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M. Gotta and M. Beller, Top. Catal., 2012, 55, 426; ( j) I. A. Sanhueza,
radicals upon H-abstraction. Both Et N and t-BuOH that are
3
1
3
present in Et
3
NÁ3HF-stabilized CuCF
3
solutions can also serve
as hydrogen sources for the aryl radical. Acetonitrile plays a
pivotal role in the reaction. As a ligand with high affinity for
I
Cu , MeCN displaces the weakly coordinating amide solvent
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K. Krogh-Jespersen and A. S. Goldman, Science, 2011, 332, 1545;
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T. G. Tampone, J. Gao, M. Sarvestani, M. C. Eriksson, N. Haddad, 18 The fluoropolymer and fluorochemical industries side-produce
S. Shen, J. J. Song and C. H. Senanayake, Org. Process Res. Dev., 2013, large quantities of CHF that is nontoxic and ozone-friendly, yet
7, 940; (l) M. Chen and S. L. Buchwald, Angew. Chem., Int. Ed., 2013,
2, 11628; (m) H. Serizawa, K. Aikawa and K. Mikami, Chem. – Eur. J.,
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E. C. Escudero-Ad ´a n, P. Nov ´a k and V. V. Grushin, J. Org. Chem., 2013,
3
1
5
2
must be destroyed or, preferably, utilized because of its high global
warming potential. See: (a) W. Han, Y. Li, H. Tang and H. Liu,
J. Fluorine Chem., 2012, 140, 7; (b) V. V. Grushin, Chim. Oggi – Chem.
Today, 2014, 32, 81.
7
8, 11126; (o) M. G. Mormino, P. S. Fier and J. F. Hartwig, Org. Lett., 19 (a) Some chemical transformations involving moisture-sensitive materials
2
014, 16, 1744.
may be efficiently conducted in water. For instance, the Schotten–
Baumann reaction of acid chlorides with amines in aqueous alkali
5
For oxidative trifluoromethylation of aryl boronic acids and boronates,
see: (a) L. Chu and F.-L. Qing, Org. Lett., 2010, 12, 5060; (b) T. D. Senecal,
A. Parsons and S. L. Buchwald, J. Org. Chem., 2011, 76, 1174; (c) J. Xu,
D.-F. Luo, B. Xiao, Z.-J. Liu, T.-J. Gong, Y. Fu and L. Liu, Chem. Commun.,
19b
produces amides because the amination of RCOCl is sufficiently
faster than its hydrolysis. Another example of seemingly illogical yet
highly successful use of aqueous media is the highly efficient
19c
2011, 47, 4300; (d) C.-P. Zhang, J. Cai, C.-B. Zhou, X.-P. Wang, X. Zheng,
synthesis of easily hydrolysable 2-pyrrolecarbaldimines in water.
;
Y.-C. Guc and J.-C. Xiao, Chem. Commun., 2011, 47, 9516; (e) T. Liu and
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and J. F. Hartwig, Angew. Chem., Int. Ed., 2012, 51, 536; (h) T. Liu,
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chemical industry has proven that HF can be safely manufactured
and used on a million-ton scale.
21b
(i) X. Jiang, L. Chu and F.-L. Qing, J. Org. Chem., 2012, 77, 1251; 21 (a) No side-formation of fluoroarenes was observed. ; (b) T. Fukuhara,
(
j) P. Nov ´a k, A. Lishchynskyi and V. V. Grushin, Angew. Chem., Int.
S. Sasaki, N. Yoneda and A. Suzuki, Bull. Chem. Soc. Jpn., 1990, 63, 2058.
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1
1
2
34, 9034; (l) Y. Ye, S. A. K u¨ nzi and M. S. Sanford, Org. Lett., 2012, 23 J. K. Kochi, J. Am. Chem. Soc., 1957, 79, 2942.
4, 4979; (m) Y. Li, L. Wu, H. Neumann and M. Beller, Chem. Commun., 24 B. Giese, B. Kopping, T. G o¨ bel, J. Dickhaut, G. Thoma, K. J. Kulicke
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G. A. Molander, J. Org. Chem., 2013, 78, 12837; (o) L. Chu and
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Radical trifluoromethylation of aromatic C–H bonds suffers from
low positional selectivity. For a recent review, see: A. Studer, Angew.
Chem., Int. Ed., 2012, 51, 8950.
J. J. Dai, C. Fang, B. Xiao, J. Yi, J. Xu, Z.-J. Liu, X. Lu, L. Liu and Y. Fu,
J. Am. Chem. Soc., 2013, 135, 8436.
and F. Trach, in Organic Reactions, ed. L. A. Paquette, et al., John
Wiley & Sons, New York, 1996, vol. 48, p. 301.
25 In contrast, the reaction of 2-allyloxyiodobenzene with fluoroform-
4
n
6
3
derived CuCF under the standard conditions produced exclusively
2-allyloxybenzotrifluoride and no traces of the cyclized product 4 (A. I.
Konovalov, results from this laboratory). This result confirms that the
formation of 4 from 3 (Scheme 3) proceeds via a 2-allyloxyphenyl
radical and that the trifluoromethylation of aryl halides with
7
8
4n
(a) G. Danoun, B. Bayarmagnai, M. F. Gr u¨ nberg and L. J. Gooßen,
fluoroform-derived CuCF
3
is not mediated by aryl radicals.
.
Angew. Chem., Int. Ed., 2013, 52, 7972; (b) One week before the 26 In the presence of Ph
2
CQCH
2
, the yield of anisole slightly decreased to
submission of the current paper, a publication from Gooßen’s
group appeared on the Web, reporting a one-pot protocol for
ca. 5% (vs. 8% in the control experiment) and a small quantity (3–5%) of
1,1-diphenyl-2-(4-methoxyphenyl)ethylene, a product of anisyl radical
addition to the CQC bond, was detected by GC-MS. In the presence
of TEMPO [(2,2,6,6-tetramethylpiperidin-1-yl)oxy], the reaction of
Cu-mediated trifluoromethylation (and trifluoromethylthiolation)
+
with CF
3
SiMe
3
of ArN
2
2
generated from ArNH , t-BuONO, and
+
À
p-TolSO
p-TolSO
3
H. Anhydrous conditions were employed. The use of
H in the form of its monohydrate lowered the yield. See:
4-MeOC
inhibited: after 15 min, 4-MeOC
(vs. ca. 70% in a control run in the absence of TEMPO). However, adding
water to this reaction mixture quickly raised the yield of 4-MeOC CF
to ca. 60%. It is likely that TEMPO coordination to the metal center of
the CuCF inhibited the reaction with the diazonium cation. Adding
TEMPO (1 equiv.) to CuCF in DMF did not lead to any visible change in
the appearance and the chemical shift (d = À26 ppm) of the CF signal
in the F NMR spectrum. After 18 h at 25 1C, however, ca. 40% of the
CuCF in this sample has decomposed. This decomposition must have
been caused by TEMPO, as in its absence less than 5% of the CuCF
6
H
4
N
2
BF
4
under anhydrous conditions was noticeably
3
6
H
4
3
CF was produced in 25% yield
B. Bayarmagnai, C. Matheis, E. Risto and L. J. Goossen, Adv. Synth.
Catal., 2014, 356, 2343.
X. Wang, Y. Xu, F. Mo, G. Ji, D. Qiu, J. Feng, Y. Ye, S. Zhang, Y. Zhang
and J. Wang, J. Am. Chem. Soc., 2013, 135, 10330.
6
H
4
3
9
3
1
1
0 D. L. Browne, Angew. Chem., Int. Ed., 2014, 53, 1482.
3
1 (a) H. Zollinger, Diazo Chemistry I: Aromatic and Heteroaromatic
Compounds, VCH, Weinheim, 1994; (b) For a recent review, see:
F. Mo, G. Dong, Y. Zhanga and J. Wang, Org. Biomol. Chem., 2013,
3
19
3
1
1, 1582.
3
13
1
1
1
2 K. Hunger, Industrial Dyes: Chemistry, Properties, Applications, Wiley,
Weinheim, 2003.
reagent would decay under such conditions. The TEMPO–CuCF
3
19
adduct (which could not be observed by F NMR because of para-
magnetism) should be more electron-deficient and therefore less reac-
3 A. Zanardi, M. A. Novikov, E. Martin, J. Benet-Buchholz and
V. V. Grushin, J. Am. Chem. Soc., 2011, 133, 20901.
4 For the remarkable mechanism of the cupration reaction of fluoro-
form, see: A. I. Konovalov, J. Benet-Buchholz, E. Martin and
V. V. Grushin, Angew. Chem., Int. Ed., 2013, 52, 11637.
5 P. Nov ´a k, A. Lishchynskyi and V. V. Grushin, J. Am. Chem. Soc., 2012,
tive toward the diazonium cation than TEMPO-free CuCF
of water freed up reactive CuCF from its TEMPO complex, thereby
promoting the trifluoromethylation.
3
. The addition
3
27 For a recent example of a Sandmeyer reaction (cyanation) mediated
by aryl radicals that do not escape the solvent cage, see: P. Hanson,
S. C. Rowell, A. B. Taylor, P. H. Walton and A. W. Timms,
J. Chem. Soc., Perkin Trans. 2, 2002, 1126.
1
1
1
1
34, 16167.
6 For related transformations involving C F H-derived CuC F , see:
2 5 2 5
A. Lishchynskyi and V. V. Grushin, J. Am. Chem. Soc., 2013, 135, 12584. 28 M. P. Doyle, J. F. Dellaria Jr., B. Siegfried and S. W. Bishop,
7 For CHF activation with transition metals other than Cu, see: J. Org. Chem., 1977, 42, 3494.
a) I. Popov, S. Lindeman and O. Daugulis, J. Am. Chem. Soc., 2011, 29 E. V. Anslyn and D. A. Dougherty, Modern Physical Organic Chemistry,
3
(
1
33, 9286; (b) J. Choi, D. Y. Wang, S. Kundu, Y. Choliy, T. J. Emge,
University Science Book, Sausalito, CA, 2006, ch. 3, p. 147.
1
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