Catalytic Oxidative Trifluoromethoxylation of Allylic C?H Bonds Using a Palladium Catalyst

Article abstract of DOI:10.1002/anie.201703841

A catalytic intermolecular allylic C?H trifluoromethoxylation reaction of alkenes has been developed based on the use of a palladium catalyst, CsOCF₃ as the trifluoromethoxide source, and benzoquinone as the oxidant. This reaction provides an efficient route for directly accessing allylic trifluoromethoxy derivatives with excellent regioselectivities from terminal alkenes via an allylic C?H bond activation process.

Full text of DOI:10.1002/anie.201703841

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: Catalytic Oxidative Trifluoromethoxylation of Allylic C-H Bonds
using a Palladium Catalyst
Authors: Guosheng Liu, Xiaoxu Qi, and Pinhong Chen
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201703841
Angew. Chem. 10.1002/ange.201703841
Link to VoR: http://dx.doi.org/10.1002/anie.201703841
http://dx.doi.org/10.1002/ange.201703841

Angewandte Chemie International Edition
10.1002/anie.201703841
COMMUNICATION
Catalytic Oxidative Trifluoromethoxylation of Allylic C-H Bonds
using a Palladium Catalyst
Xiaoxu Qi, Pinhong Chen, and Guosheng Liu*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese
Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Supporting Information
Abstract:
trifluoromethoxylation of alkenes has been developed using
palladium catalyst, in which CsOCF was employed as the
A
novel catalytic intermolecular allylic C-H
a
3
trifluoromethoxide source and BQ as the oxidant. This reaction
provides an efficient route for directly accessing allylic
trifluoromethoxy ether derivatives with excellent regioselectivities
from terminal alkenes via an allylic C-H bond activation process.
The selective transformations of C-H bonds have emerged as an
efficient and atom-economical tool for the organic
[
1]
transformations, and tremendous efficient methods have been
[2]
reported. Due to the importance of organofluorine compounds in
[
3]
pharmaceutical, agrochemicals, and material science, the direct
[
4
]
[
5
]
oxidative fluorination,
trifluoromethylthiolation
trifluoromethylation,
and
Scheme 1. Catalytic Oxidative Trifluoromethoxylations.
[
6 ]
of C-H bonds have received much
[7]
attention. Distinct from these reactions, the easy decomposition
[12]
under the mild condition (room temperature).
Considering the
property of an OCF anion and limited range of trifluoromethoxide
3
nature of trifluoromethoxide, we reasoned that, compared to other
reactions, palladium-catalyzed allylic C–H activation of alkenes
might be a suitable mode reaction to test the possibility of C-H
reagents cause the extreme difficulty to carry out catalytic
[
8]
trifluoromethoxylation reaction. Recently, we reported the first
catalytic oxidative trifluoromethoxylation of alkenes through a
trifluoromethoxylation. Distinct from previous trifluoro-
o
[9]
Pd(II/IV) cycle at -20 C (Scheme 1a). However, unlike those
difunctionalization reactions of alkenes which take place under
[9]
methoxylation involving
a high-valent palladium species,
however, allylic C-H functionalization generally undergoes a
Pd(0/II) catalytic cycle. Vicic and coworkers demonstrated that
[
10 ]
mild conditions,
most of C-H bond functionalizations often
[
2,4-6]
proceed under harsh reaction conditions,
which significantly
I
I
low-valent (NHC)Cu OCF and (NHC)Au OCF complexes are
extremely unstable.
3
3
impede applying instable CF O reagents for the new catalytic
[ 13 ]
3
Thus, the question is that how fast
design. Thus, the oxidative trifluoromethoxylation of C-H bonds
remains intact so far. Herein, we reported our success on the
catalytic allylic C-H oxidative trifluoromethoxylation using a
trifluoromethoxide decomposes within a Pd(0/II) cycle, and how to
retard this side reaction?
In fact, fast AgOCF decomposition was observed in our initial
3
palladium catalyst. The slow generation of AgOCF from an easily
3
reaction of 1a with Pd(OAc) /AgOCF /BQ system at room
[
11]
2
3
synthesized and thermo-stable CsOCF3 is crucial for the reaction
temperature, accompanied with a small amount of desired product
a (table 1, entry 1). Although Szabó and coworkers reported that a
(Scheme 1b).
2
In the last decade, groundbreaking achievement on the
palladium-catalyzed oxidative functionalization of allylic C-H
bonds has been obtained, and most of reactions proceed smoothly
[12g]
Pd(II/IV) catalytic cycle is good for allylic acetoxylation,
but
similar reaction conditions are failed in this trifluoromethoxylation.
None or trace product 2a (< 3%) was detected in the presence of
strong oxidants, such as SelectFluor, NFSI, I(III) reagents (see SI).
Catalysts screening revealed that PdCl (MeCN) was superior to
2
2
other Pd catalysts to give product 2a in 20% yield (entries 2-3).
Due to the fast decomposition of AgOCF , further optimizing
reaction condition was failed to improve the reaction yield, along
3
[*]
X. Qi, Dr. P. Chen, Prof. Dr. G. Liu
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, University of Chinese Academy of
Sciences, Chinese Academy of Sciences
with the side fluorination product. Furthermore, other OCF
3
[ 14 ]
sources, such as CsOCF , Me NOCF and TASOCF3,
were
3
4
3
ineffective (entries 4-6). These observations indicated that silver
plays an important role in the trifluoromethoxylation, in spite of a
3
45 Lingling Road, Shanghai, 200032 (China)
E-mail: gliu@mail.sioc.ac.cn
Homepage: http://guoshengliu.sioc.ac.cn/
heavy side decomposition of AgOCF . In order to alleviate this
3
side reaction, we surmised that slowly generating AgOCF in situ
3
Supporting information for this article is given via a link at the end of the
document.
from poor soluble OCF salts might be beneficial. After extensive
3
screening, the combination of AgBF (1.2 equiv.) and CsOCF (3.0
4
3
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201703841
COMMUNICATION
a
equiv.) provided a better result to generate 2a in 39% yield (entries
Table 2. Substrate scope of allylic C-H trifluoromethoxylation.
[
11a]
7
-8). Meanwhile, owing to the equilibrium in eq 1,
we reasoned
that the addition of extraneous AgF might be helpful to retard the
decomposition in a sealed bottle. Indeed, the reaction yield was
increased to 46% by adding AgF (entry 9). Furthermore, the yield
could be slightly increased to 51% by increasing the amount of
CsOCF to 3.5 equivalents (entry 10). Adding catalytic amount of
3
carboxylic acid (A1) and slightly increasing the palladium catalyst
loading (15 mol %) were beneficial to the reaction (76% yield,
entries 11-12); Alternative 2,4,6-trimethylbenzoic acid (A2) gave a
slightly better yield (78%, entry 13). The addition of 2,4,6-
trimethylbenzoic acid A2 could accelerate the reaction rate (See the
Supporting Information). Finally, the best yield was given by
increasing the reaction concentration with PdCl (PhCN) (entries
2
2
1
4-15). Notably, the trifluoromethoxylation reaction did not occur
in the absence of either Pd(II) catalyst or BQ (entries 16-17). It is
worth noting that, all of these reactions exhibited excellent regio-
and stereoselectivity to give linear product E-2a at room
temperature.
a,b
Table 1. Optimization of reaction conditions.
yields. Notably, the reaction of substrate bearing pentafluorophenyl
provided product 2p in 56% yield, and product 2q containing OTf
moiety allows for the further transformation. In addition to allyl
benzene derivatives, allyl naphthalene, indole, coumarin and other
heteroarenes such as pyridine and benzothiophene were proved as
suitable substrates to give products 2r-2w in moderate yields (40-
With the optimized reaction conditions in hand, the substrate scope
was examined, and the results were summarized in Table 2. A
variety of allyl arenes bearing both electron-rich (1a-1c and 1l-1m)
and electron-poor (1e-1k) substituents on the aryl ring were
suitable to afford the corresponding linear E-configuration products
6
4%). Finally, more complex molecules were also evaluated. For
example, substrates bearing steroid scaffold with free-alcohol (1x)
or protected ester (1y) were compatible with the reaction condition,
and provided products 2w (41%) and 2x (58%), respectively.
Meanwhile, when substrate 1z with estrone moiety was subjected
to the standard reaction conditions, product 2z was obtained in
good yield (57%). It is noteworthy that, the reaction could be
scaled up to provide product 2g in excellent yield (82% in 5.5
mmol, 1.58 g). Unfortunately, this transformation is limited on the
allyl arene substrates. Other terminal alkenes and cyclic aliphatic
alkenes, such as 1-octene or cyclohexene were ineffective to give
trace amount of the desired products with substrate remained.
2
a-2k in moderate to good yields with excellent regio- and stereo-
selectivities. In addition, various functional groups on the aryl ring,
such as halogen (2e, 2f), triflate (2g), trifluoromethyl (2h),
carboxylic ester (2i), ketone (2j) and nitrile (2k), were tolerated
under the reaction conditions. The compatible aryl bromide (2f)
and aryl triflate (2g) also provided opportunities for further
transformations. For the multi-substituted allyl arenes, the reactions
also proceeded smoothly to afford products (2o-2q) in satisfactory
To demonstrate potential application of these allylic
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201703841
COMMUNICATION
3
trifluoromethoxylation products, as shown in Scheme 2, the
epoxidation of product 2a was achieved with m-CPBA to provide a
single isomer E-3 in 78% yield, which could act as a valuable
KIE (k /k = 2.6, eq 6). These values suggest that allylic C(sp )–H
bond activation contributes to the turnover-limiting step.
H
D
OCF -containing synthon to access
a
wide array of
3
trifluoromethoxylated building blocks. For instance, the epoxide
could be attacked by either azide or Grigard reagent to give single
isomers 4a (73% yield) or 4b (75% yield) stereosepcifically.
Meanwhile, treatment by strong Lewis acid Sc(OTf) , the epoxide
3
compound 3 could be efficiently converted to product α-OCF3
ketone 4c in 64% yield.
NaN , LiClO
4
N3
m-CPBA
NaHCO3
O
3
OCF3 MeCN, 55 o
C
OCF3
2a
DCM,
OH
Based on the above analysis, a proposed mechanism was shown
in Scheme 3. First, the reaction was initiated by a Pd(II)-catalyzed
allylic C-H bond activation to give an -allyl-Pd(II) intermediate II,
Ph
Ph
3
78%
4
a 73%
Allyl-MgCl
DCM, 0 oC-rt
Sc(OTf)3
THF/H2O, rt, 24 h
followed by a S 2 nucleophilic attack by trifluoromethoxide to
N
give the desired trifluoromethoxylation products, which was
OCF3
OCF3
promoted by BQ coordination. The released Pd(0) catalyst was
O
OH
Ph
[17]
Ph
oxidized by BQ to regenerate Pd(II) catalyst.
Herein, the rate-
4c 64%
4b 75%
determining allylic C-H bond activation resulted in a competitive
Scheme 2. Further transformations.
To get more insight into the reaction mechanism, π-allyl-Pd dimer
decomposition of AgOCF in the presence of Pd (II) catalyst. To
3
alleviate this side reaction, two key features were crucial for the
success of this transformation: (1) the addition of carboxylic acid
A2 can accelerate allylic C-H activation step (see SI); (2)
5
was synthesized and treated with AgBF /CsOCF /AgF. Similar to
4 3
the catalytic reaction, the reaction only took place in the presence
of BQ (eq 2). This observation indicated that BQ should act as a π-
acceptor ligand to activate π-ally-Pd intermediate, promoting the
employing poorly soluble and stable CsOCF can gradually release
3
active trifluoromethoxide reagent AgOCF , which could lower its
3
[15]
concentration to slow down the decomposition step.
fast nucleophilic attack by OCF anion. Meanwhile, -allyl-Pd
3
complex
6 (cis/trans = 4/1) was applied to address the
stereochemistry. As shown in eq 3, the trifluoromethoxylation
reaction of 6 afforded major trans-7 (cis/trans = 1/4), suggesting a
stereo-configuration inversion pathway. Although the detailed
mechanism is still unclear, we believe that the C-OCF bond
3
formation might occur via an outer-sphere nucleophilic substitution
pathway by AgOCF . However, an alternative intermolecular
3
bimetallic pathway with another -allyl-Pd(OCF ) complex cannot
3
[16]
be excluded.
Scheme 3. Plausible reaction mechanism.
In conclusion, the first allylic C-H trifluoromethoxylation
reaction has been developed by using a palladium catalyst, which
provides a new approach to synthesize OCF -containing organic
3
molecules efficiently. Importantly, the current study reveals that
the catalytic trifluoromethoxylation could be achieved through a
Pd(0/II) catalytic cycle under room temperature. Moreover, the
slowly releasing key AgOCF reagent is vital. Further exploration
3
of new trifluoromethoxylation reaction is ongoing in our laboratory.
Furthermore, the competitive reactions between allyl benzene (1d)
and para-substituted allyl benzenes (1c, 1h or 1k) were conducted,
and the results indicated that electron-poor substrates (1h, 1k)
were preferred to give major products 2h and 2k (eq 4). This
observation indicated that the allylic C-H activation is prior to
occur at an allylic carbon center with more acidic proton.
Acknowledgements
We are grateful for financial support from the National Basic
Research Program of China (973-2015CB856600), the National
Nature Science Foundation of China (Nos. 21225210, 21532009,
2
1472219 and 21421091), Program of Shanghai Academic/
Technology Research Leader (17XD1404500), the strategic
Priority Research Program of the Chinese Academy of Sciences
(No. XDB20000000). This research was partially supported by
CAS Interdisciplinary Innovation Team.
In addition, the competitive deuterium kinetic isotopic effects (KIE)
study, using a mixture of 1a and d -1a, revealed a significant KIE
2
Keywords: alkenes • trifluoromethoxylation • C-H activation •
(
k /k ) of 4.6 (eq 5). On the other hand, independent measurement
H D
palladium catalyzed
of the reaction rate of these two substrates still provided a large
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201703841
COMMUNICATION
[
1] a) R. H. Crabtree, Chem. Rev. 2010, 110, 575; b) A. E. Shilov, G. B.
Shul’pin, Chem. Rev. 1997, 97, 2879.
Fluorine Chem. 2010, 131, 200. d) O. Marrec, T. Billard, J.-P. Vors, S.
Pazenok, B. R. Langlois, Adv. Synth. Catal. 2010, 352, 2831. e) J.-B.
Liu, X.-H. Xu, F.-L. Qing, Org. Lett. 2015, 17, 5048. f) C. Huang, T.
Liang, S. Harada, E. Lee, T. Ritter, J. Am. Chem. Soc. 2011, 133, 13308.
g) G.-F. Zha, J.-B. Han, X.-Q. Hu, H.-L. Qin, W.-Y. Fang, C.-P. Zhang,
Chem. Commun. 2016, 52, 7458. h) K. N. Hojczyk, P. Feng, C. Zhan,
M.-Y. Ngai, Angew. Chem. Int. Ed. 2014, 53, 14559. i) P. Feng, K. N.
Lee, J. W. Lee, C . Zhan, M.-Y. Ngai, Chem. Sci. 2016, 7, 424. j) S.
Guo, F. Cong, R. Guo, L. Wang, P. Tang, Nat. Chem. 2017, 9, 546.
[9] C. Chen, P. Chen, G. Liu, J. Am. Chem. Soc. 2015, 137, 15648.
[10] G. Yin, X. Mu, G. Liu, Acc. Chem. Res. 2016, 49, 2413.
[2] For some reviews, see: a) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010,
1
10, 1147; b) D. A. Colby, R. G. Bergman, J. A. Ellman , Chem.
Rev. 2010, 110, 624; c) C. S. Yeung, V. M. Dong, Chem. Rev. 2011,
11, 1215; d) L. Ackermann, Chem. Rev. 2011, 111, 1315; e) R.-Y. Zhu,
1
M. E. Farmer, Y.-Q. Chen; J.-Q. Yu, Angew. Chem. Int.
Ed. 2016, 55, 10578; f) T. Gensch, M. N. Hopkinson, F. Glorius, J.
Wencel-Delord, Chem. Soc. Rev. 2016, 45, 2900.
[3] a) R. Filler, Y. Kobayashi, Biomedicinal Aspects of Fluorine Chemistry,
Elsevier, Amsterdam, 1982; b) Fluorine in Bioorganic Chemistry
(
Eds.:J. T. Welch, S. Eswarakrishman), Wiley, New York, 1991; c)
Organofluorine Chemistry: Principles and Commercial Applications
Eds.: R. E. Banks, B. E. Smart, J. C. Tatlow), Plenum Press, New York,
994.
[11] The stability of ionic trifluoromethoxide is significantly influenced by
the nature of cation, and the salt with larger size cation is more stable.
For details, see: a) M. E. Redwood, C. J. Willis, Can. J. Chem. 1965,
(
1
3
43, 1893. Meanwhile, the poor solubility of CsOCF in aprotic solvent
[
4] For some selected examples on C-H bond fluorinations, see: a) K. L.
Hull, W. Q. Anani, M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 7134;
b) X. Wang, T.-S. Mei, J.-Q. Yu, J. Am. Chem. Soc. 2009, 131, 7520;
c) A. W. Kaspi, I. Goldberg, A. Vigalok, J. Am. Chem. Soc. 2010, 132,
is another reason to result good stability, see: b) A. A. Kolomeitsev, M.
Vorobyev, H. Gillandt, Tetrahedron Lett. 2008, 49, 449.
[12] For some selected examples on the oxidative oxygenation of allylic C-
H bonds, see: a) M. S. Chen, M. C. White, J. Am. Chem. Soc. 2004,
126, 1346. b) M. S. Chen, N. Prabagaranm, N. A. Labenz, M. C.
White, J. Am. Chem. Soc. 2005, 127, 6970. c) T. Mitsudome, T.
Umetani, N. Nosaka, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda,
Angew. Chem. Int. Ed. 2006, 45, 481. d) D. J. Covell, M. C. White ,
Angew. Chem. Int. Ed. 2008, 47, 6448. e) A. N. Campbell, P. B. White,
I. A. Guzei, S. S. Stahl, J. Am. Chem. Soc. 2010, 132, 15116. f) C. T.
Check, W. H. Henderson, B. C. Wray, M. J. Vanden Eynden, J. P.
Stambuli, J. Am. Chem. Soc. 2011, 133, 18503. g) R. Alam, L. T.
Pilarski, E. Pershagen, K. J. Szabó, J. Am. Chem. Soc. 2012, 134, 8778.
h) P.-S. Wang, P. Liu, Y.-J. Zhai, H.-C. Lin, Z.-Y. Han, L.-Z. Gong,
J. Am. Chem. Soc. 2015, 137, 12732. Amination, see: i) K. J.
Fraunhoffer, M. C. White, J. Am. Chem. Soc. 2007, 129, 7274. j) L.
Wu, S. Qiu, G. Liu, Org. Lett. 2009, 11, 2707. k) S. A. Reed, M. C.
White, J. Am. Chem. Soc. 2008, 130, 3316. l) G. Liu, G. Yin, L. Wu,
Angew. Chem. Int. Ed. 2008, 47, 4733. m) M. R. Luzung, C. A. Lewis,
P. S. Baran, Angew. Chem. Int. Ed. 2009, 48, 7025. n) G. Yin, Y. Wu,
G. Liu, J. Am. Chem. Soc. 2010, 132, 11987. Alkylation, see: o) S. Lin,
C.-X. Song, G.-X. Cai, W.-H. Wang, Z.-J. Shi, J. Am. Chem. Soc. 2008,
130, 12901. p) J. H. Delcamp, A. P. Brucks, M. C. White, J. Am. Chem.
Soc. 2008, 130, 11270. q) P.-S. Wang, H.-C Lin, Y.-J. Zhai, Z.-Y. Han,
L.-Z. Gong, Angew. Chem. Int. Ed, 2014, 53, 12218. r) H.-C. Lin, P.-S.
Wang, Z.-L. Tao, Y.-G. Chen, Z.-Y. Han, L.-Z. Gong, J. Am. Chem.
Soc. 2016, 138, 14354. Other reactions, see: s) J. M. Larsson, T. S. N.
Zhao, K.J. Szabó, Org. Lett. 2011, 13, 1888. t) M.-G. Braun, A. G.
Doyle, J. Am. Chem. Soc. 2013. 135, 12990. u) H. Chen, C. Cai, X. Liu,
X. Li, H.-F. Jiang, Chem. Commun. 2011, 47, 12224.
1
2
0626; d) T. Truong, K. Klimovica, O. Daugulis, J. Am. Chem. Soc.
013, 135, 9342; e) R.-Y. Zhu, K. Tanaka, G.-C. Li, J. He, H.-Y.
Fu, S.-H. Li, J.-Q. Yu, J. Am. Chem. Soc. 2015, 137, 7067; f) Q. Zhang,
X.-S. Yin, K. Chen, S.-Q. Zhang, B.-F. Shi, J. Am. Chem.
Soc. 2015, 137, 8219.
[
5] For some selected examples on the C-H bond trifluoromethylations, see:
a) X. Wang, L. Truesdale, J.-Q. Yu, J. Am. Chem. Soc. 2010, 132, 3648;
b) X. Mu, S. Chen, X. Zhen, G. Liu, Chem. Eur. J. 2011, 17, 6039; c)
L.-L. Chu, F. L. Qing, J. Am. Chem. Soc. 2010, 132, 7262; d) J. Xu, Y.
Fu, D. Luo, Y. Jiang, B. Xiao, Z. Liu, T. Gong, L. Liu, J. Am. Chem.
Soc. 2011, 133, 15300; e) X. Wang, Y. Ye, S. Zhang, J. Feng, Y. Xu, Y.
Zhang, J. Wang, J. Am. Chem. Soc. 2011, 133, 16410; f) A. T. Parsons,
S. L. Buchwald, Angew. Chem., Int. Ed. 2011, 50, 9120; g) L. Chu, F.-L.
Qing, J. Am. Chem. Soc. 2012, 134, 1298; h) X.-G. Zhang, H.-X. Dai,
M. Wasa, J.-Q. Yu, J. Am. Chem. Soc. 2012, 134, 11948; i) M. Miura,
C.-G. Feng, S. Ma, J.-Q. Yu, Org. Lett. 2013, 15, 5258; j) M. Shang, S.-
Z. Sun, H.-L.Wang, B. N. Laforteza, H.-X. Dai, J.-Q. Yu, Angew.
Chem., Int. Ed. 2014, 53, 10439; k) T. Nishida, H. Ida, Y. Kuninobu, M.
Kanai, Nat. Commun. 2014, 5, 3387; l) J. W. Beatty, J. J. Douglas, K. P.
Cole, C. R. J. Stephenson, Nat. Commun. 2015, 6, 7919. m) L. Li, X.-Y.
Mu, W.-B. Liu, Y.-C. Wang, Z.-T. Mi, C.-J. Li, J. Am. Chem. Soc. 2016,
1
38, 5809.
[
6 ] For some selected examples on the C-H bond trifluoromethyl-
thiolations, see: a) L. D. Tran, I. Popov, O. Daugulis, J. Am. Chem.
Soc. 2012, 134, 18237. b) A.; Ferry, T. Billard, E. Bacque, B. R.
Langlois, J. Fluorine Chem. 2012, 134, 160. c) Y.-D. Yang, A. Azuma,
E. Tokunaga, M. Yamasaki, M. Shiro, N. Shibata, J. Am. Chem. Soc.
[13] C. Zhang, D. A. Vicic, Organometallics 2012, 31, 7812.
2
013, 135, 8782. d) C. Xu, Q. Shen, Org. Lett. 2014, 16, 2046. e) C.
[14] TASOCF3 = tris(dimethylamino)sulfoniumtrifluoromethoxide.
[15] For some selected examples of BQ-promoted reductive elimination ,
see refs 12b, 12n and a) J. E. Bäckval, S. E. Byström, R. E. Nordberg, J.
Org. Chem. 1984, 49, 4619; b) X. Chen, J. J. Li, X. S. Hao, C. E.
Goodhue, J. Q. Yu, J. Am. Chem. Soc. 2006, 128, 78; c) a) K. L. Hull,
M. S. Sanford, J. Am. Chem. Soc. 2007, 129, 11904; d) K. L. Hull, M.S.
Sanford, J. Am. Chem. Soc. 2009, 131, 9651; e) T. W. Lyons, K. L. Hull,
M. S. Sanford, J. Am. Chem. Soc. 2011, 133, 4455.
Chen, X.-H. Xu, B. Yang, F.-L. Qing, Org. Lett. 2014, 16, 3372. f) J.
Xu, P. Chen, J. Ye, G. Liu, Acta. Chem. Sinica. 2015, 73, 1294. g) H.
Wu, Z. Xiao, J. Wu, Y. Guo, J.-C. Xiao, C. Liu, Q.-Y. Chen, Angew.
Chem. Int. Ed. 2015, 54, 4070. h) S. Guo, X. Zhang, P. Tang, Angew.
Chem. Int. Ed. 2015, 54, 4065. i) S. Mukherjee, B. Maji, A. Tlahuext-
Aca, F. Glorius, J. Am. Chem. Soc. 2016, 138, 16200.
(
7) a) X. Yang, T. Wu, R. J. Phipps, F. D. Toste, Chem. Rev. 2015, 115,
8
26. b) P. Chen, G. Liu, Synthesis 2013, 45, 2919. c) Y. Ye, M. S.
[16] The similar stereochemistry was observed in the allylic C-H oxidative
fluorination, in which a homobimetallic nucleophilic substitution
pathway was reported by Doyle and coworkers. For details, see: M. H.
Katcher, P.-O. Norrby, A. G. Doyle, Organometallics 2014, 33, 2121.
[17] Ag(I) could also act as oxidant to ahieve Pd(II) regeneration, and this
possibility can not be excluded at the stage. For details, see ref. 15c-
15e and B.-F. Shi, N. Maugel, Y.-H. Zhang, J.-Q. Yu, Angew. Chem.
Int. Ed. 2008, 47, 4882;
Sanford, Synlett 2012, 23, 2005. (d) X.-F. Wu, H. Neumann, M. Beller,
Chem.–Asian. J. 2012, 7, 1744.
8] For recent reviews on the trifluoromethoxylations, see a) T. Besset, P.
Jubault, X. Pannecoucke, T. Poisson, Org. Chem. Front. 2016, 3, 1004.
b) A. Tlili, F. Toulgoat, T. Billboard, Angew. Chem. Int. Ed. 2016, 55,
[
1
1726. For some examples on the direct trifluoromethoxylations, see: c)
O. Marrec, T. Billard, J.-P. Vors, S. Pazenok, B.R. Langlois, J.
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201703841
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
X. Qi, P. Chen, G. Liu *
Page No. – Page No.
Title: Catalytic Oxidative
Trifluoromethoxylation of Allylic C-H
Bonds using a Palladium Catalyst
Text for Table of Contents
A novel catalytic intermolecular allylic C-H trifluoromethoxylation of alkenes has been
3
developed using a palladium catalyst, in which CsOCF was employed as the
trifluoromethoxide source and BQ as the oxidant. This reaction provides an efficient
route for directly accessing allylic trifluoromethoxy ether derivatives with excellent
regioselectivities from terminal alkenes via an allylic C-H bond activation process.
This article is protected by copyright. All rights reserved.