Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation of Alkenes with Alcohols

Article abstract of DOI:10.1002/anie.201702925

A conceptually novel strategy with achiral pyridine as the ancillary ligand to stabilize high-valent copper species for the first asymmetric radical oxytrifluoromethylation of alkenes with alcohols under Cu^I/phosphoric acid dual-catalysis has been developed. The transformation features mild reaction conditions, a remarkably broad substrate scope and excellent functional group tolerance, offering an efficient approach to a wide range of trifluoromethyl-substituted tetrahydrofurans bearing an α-tertiary stereocenter with excellent enantioselectivity. Mechanistic studies support the presumed role of the achiral pyridine as a coordinative ligand on copper metal to stabilize the key transient reaction species involved in the asymmetric induction process.

Full text of DOI:10.1002/anie.201702925

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201702925
German Edition: DOI: 10.1002/ange.201702925
Asymmetric Catalysis
Achiral Pyridine Ligand-Enabled Enantioselective Radical
Oxytrifluoromethylation of Alkenes with Alcohols
Yong-Feng Cheng+, Xiao-Yang Dong+, Qiang-Shuai Gu+, Zhang-Long Yu, and Xin-Yuan Liu*
Dedicated to Professor Shizheng Zhu on the occasion of his 70th birthday
Abstract: A conceptually novel strategy with achiral pyridine
as the ancillary ligand to stabilize high-valent copper species
for the first asymmetric radical oxytrifluoromethylation of
alkenes with alcohols under CuI/phosphoric acid dual-catalysis
has been developed. The transformation features mild reaction
conditions, a remarkably broad substrate scope and excellent
functional group tolerance, offering an efficient approach to
a wide range of trifluoromethyl-substituted tetrahydrofurans
bearing an a-tertiary stereocenter with excellent enantioselec-
tivity. Mechanistic studies support the presumed role of the
achiral pyridine as a coordinative ligand on copper metal to
stabilize the key transient reaction species involved in the
asymmetric induction process.
Chiral trifluoromethyl (CF3)-containing heterocycles have
been gaining increasing interest in agrochemicals, pharma-
ceuticals and molecular materials because of the unique effect
of the fluorine atom on physical and biological properties of
many chemicals.[1] As a result, very impressive advances have
been achieved in the development of radical intramolecular
difunctionalization-type trifluoromethylation of alkenes to
construct different types of CF3-containing heterocycles.[2]
However, the catalytic asymmetric variants remain a formi-
dable challenge with few successful examples[3–5] largely
because of the difficulty related to the stereochemical control
of the involved odd-electron species.[3] In this context, we
have recently discovered that a CuI/chiral phosphoric acid
(CPA) dual-catalytic system realized asymmetric aminotri-
fluoromethylation of alkenes (Scheme 1b).[5,6] Nevertheless,
the incapability of known catalytic systems to tackle the
remaining challenges has become more and more obvious and
thus new strategies are highly desirable for further developing
efficient asymmetric radical difunctionalization-type trifluor-
omethylation reactions with versatile trapping reagents.
Chiral oxygen heterocycles, such as tetrahydrofurans
bearing a-tertiary stereocenters at the C2 positions, are
important structural motifs in numerous biologically active
compounds and pharmaceutical agents.[7] Consequently, the
Scheme 1. Asymmetric radical difunctionalization-type trifluoromethyla-
tion of alkenes.
direct asymmetric construction of a-tertiary tetrahydrofurans
has long been recognized as a preeminent goal for organic
synthesis.[8] Given the apparent gaps in existing synthetic
methodology, we became interested in developing asymmet-
ric radical oxytrifluoromethylation of alkenes with alcohols to
access enantioenriched functionalized a-tertiary tetrahydro-
furans. However, direct stereochemical control over the
reaction between a highly reactive alkyl radical intermediate
and an alcohol has proved problematic. Notably, alcohol-
based nucleophiles have been found to be incompatible with
the copper-bis(oxazoline) catalyst system employed by Buch-
wald (Schemes 1a and c, and Scheme S1 in the Supporting
Information), presumably because of the low binding affinity
of alcohols toward chiral metal centers.[4a,b] We had envisaged
the possibility of using the hydroxy group as a hydrogen-
bonding donor to anchor CPA-ligated copper catalyst for
stereoinduction. However, our attempts to address this
challenge by employing our developed CuI/CPA dual-cata-
lytic system (Scheme 1b)[5] met with poor enantioselectivity
(Scheme 1d, and Scheme S1). In our previous work, we have
observed that the enantioselectivity of aminotrifluoromethy-
lation significantly depended on the presence of an intact urea
[*] Dr. Y.-F. Cheng,[+] X.-Y. Dong,[+] Dr. Q.-S. Gu,[+] Z.-L. Yu, Prof. X.-Y. Liu
Department of Chemistry
South University of Science and Technology of China
Shenzhen, 518055 (P.R. China)
E-mail: liuxy3@sustc.edu.cn
À
[+] These authors contributed equally to this work.
moiety bearing two acidic N H bonds. The hydroxy group
involved in the current transformation is inherently much
weaker than such urea in terms of their capability as
a hydrogen-bonding donor and further as an efficient
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.201702925.
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

Angewandte
Communications
Chemie
anchor for the CPA-ligated copper catalyst. This may have
resulted in strong non-enantioselective background reaction
with poor stereocontrol. On the basis of these observations,
a conceptually different approach is highly demanded to
achieve highly efficient asymmetric radical oxytrifluorome-
thylation of alkenes with alcohols.
chemistry. Among these copper salts examined, CuBH4-
(PPh3)2 bearing PPh3 ligand was found to be particularly
effective in terms of enantioselectivity (entry 6, 77% ee). In
order for better enantioselectivity, a variety of achiral
pyridine derivatives were then screened (entries 10 and 11,
and Figure S3a). Both the position and the electronic
property of the substituents on the pyridine ring had
a significant effect on the efficiency and the stereoselectivity
of this radical reaction, and N,N-diethylnicotinamide P1
proved to be the optimum one to give 3A in 87% yield and
91% ee (entry 11). Finally, the use of a mixed solvent system
of AcOiPr/c-hexane (9/1) further improved enantioselectivity
to 93% ee (entry 12). The use of other Cu salts such as CuI or
CuCN instead of CuBH4(PPh3)2 provided slightly inferior
enantioselectivity under the otherwise optimal reaction con-
ditions (entries 13, 14).
With the optimal reaction conditions established, we next
investigated the substrate scope of alkenols (Table 2). We first
explored gem-disubstituted alkenols bearing different tether-
ing groups and found a series of alkenols containing three- to
seven-membered rings were well tolerated to provide a set of
spiro-products 3A–3E in 64–88% yields with 90–97% ee.
Changing the cyclic groups to two methyl groups in the tether
had no significant influence on the reaction, giving 3F with
comparable efficiency and enantioselectivity. Next, a range of
diversely functionalized alkenols 1G–1Q, including those
having mono-substituted phenyl rings with electron-donating
or -withdrawing groups at different positions (ortho, meta or
It is well-known that Lewis bases can have a profound
influence on the stability of high-valent organo-Cu(II/III)
species, affecting their reactivity toward oxidative addition
and/or carbon-carbon(heteroatom) bond-forming reductive
elimination.[9,10] In light of this knowledge, we questioned
whether introducing an ancillary achiral Lewis base would
elicit high enantioselectivity by stabilizing high-valent copper
species int-II and int-III, which have been postulated as key
intermediates in previous related reactions (Scheme 1e).[4,5]
Herein we report the successful realization of this new
strategy using achiral pyridine as an ancillary ligand, thus
enabling an unprecedented asymmetric radical oxytrifluoro-
methylation of alkenes with alcohols catalyzed by a dual
system of CuI and CPA (Scheme 1e). Notably, this work
represents the first successful example of achiral additive-
enabled highly enantioselective radical reactions.[10]
To probe the feasibility of our assumption, we first
evaluated the impact of incorporating catalytic achiral
pyridine as an additive into a dual-catalytic system of CuI
and (R)-VAPOL hydrogenphosphate A6 (Table 1). We were
encouraged to observe a significant increase in enantioselec-
tivity from 21% ee to 70% ee obtained in the absence and
presence of pyridine (entries 1 and 2), respectively. Changes
of ligands and anions in copper salts led to profound
variations in both the efficiency and the enantioselectivity
(entries 2–6), likely suggesting that these achiral ligands/
anions were critical for stabilizing the presumed transient
reaction species and thus tuning their reactivity and stereo-
Table 2: Substrate scope.[a,b,c]
Table 1: Screening of reaction conditions.[a]
entry
[Cu]
LB
solvent
y [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
CuI
CuI
CuBr
CuCl
CuPF6(MeCN)4
CuBH4(PPh3)2
CuBH4(PPh3)2
CuBH4(PPh3)2
CuBH4(PPh3)2
CuBH4(PPh3)2
CuBH4(PPh3)2
CuBH4(PPh3)2
CuI
–
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
DCM
90
88
87
85
50
87
86
40
45
87
87
88
83
88
21
70
43
42
51
77
72
77
77
80
91
93
84
89
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
P1
MeCN
c-Hexane
AcOiPr
AcOiPr
9
10
11
12
13
14
[d]
P1
P1
P1
–
[d]
–
[d]
CuCN
–
[a] Reaction conditions: 1a (0.05 mmol), 2a (1.5 equiv), CuI (10 mol%),
(R)-A6 (15 mol%), Lewis base (13 mol%), solvent (0.5 mL), 258C, 36 h
under argon. [b] Yield based on 1H NMR analysis of the crude product
using trifluoromethoxybenzene as an internal standard. [c] Ee value
based on HPLC analysis. [d] AcOiPr/c-Hexane (9/1) was used as solvent.
[a] All the reactions were conducted on 0.2 mmol scale. [b] Yield was
isolated one based on 1. [c] Ee was determined by HPLC analysis.
[d] 1,1,1,3,3,3-Hexafluoro-2-propanol (0.4 equiv) was added. [e] Reaction
temperature: 608C; conversion: 60%.
2
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
These are not the final page numbers!

Angewandte
Communications
Chemie
para) and a dimethyl-substituted phenyl ring as well as
These results indicate that copper(I) is essential as a single-
a polyarene naphthalene ring, were found to be suitable
substrates to afford 3G–3Q in 61–81% yields with 80–97% ee
(Table 2). Furthermore, many common functional groups,
such as ester (3R), amide (3S), nitrile (3T) and even nitro
(3U) ones, were all compatible with the reaction conditions.
Potentially reactive free aldehyde (3V) and alcohol (3W)
were well tolerated, without the need for protecting groups in
spite of the oxidative nature of this process. In addition,
substrates containing the other reactive double or triple bonds
afforded corresponding products 3X and 3Y with the addi-
tional double or triple bonds intact. More importantly,
substrate 1z without gem-disubstituents together with sub-
strates featuring a heteroaryl-substituted alkene moiety or
a 5-hexenol skeleton for the formation of a pyran ring
(Scheme 3S) all underwent the current reaction with unsat-
isfactory but promising enantioselectivity, which warrant
further condition optimization. These features indicate the
great functional group tolerance (halides, ester, amide, nitrile,
nitro, aldehyde, hydroxy, alkene and alkyne groups) of this
reaction with unique chemoselectivity, highlighting the gen-
erality of this transformation and offering opportunities for
further versatile modifications. The absolute configuration of
3V has been determined by X-ray structural analysis on its
hydrazone derivative.[11]
electron transfer catalyst to reduce Togniꢀs reagent in order
for generating CF3 radical and the activation of Togniꢀs
reagent could be facilitated by the phosphoric acid
[Eq. (1)].[13]
Then some experiments were conducted to ascertain the
role of pyridine in this reaction. In our reaction system,
pyridine derivatives could act either as a Lewis basic ligand on
copper metal[9] or as a Brønsted base (proton shuttle)[10c] to
facilitate deprotonation of alcohol. In support for the ligand
role, our initial high-resolution mass spectrometry analysis of
a reaction mixture identified a CuI-P1 complex formed from
CuBH4(PPh3)2 and P1 by ligand exchange (Figure S2). To
further provide support for pyridine as an ancillary ligand,[10]
we have surveyed a range of electronically differentiated
pyridines for this reaction (Table 1, and Figure S3a) and
found that a certain level of coordinating capability toward
copper but not Brønsted basicity is necessary for maintaining
high enantioselectivity. In particular, poorly coordinating 2,6-
di-tBu-pyridine with a pKa value (4.95 in water, Table S1)
within the optimal pKa window (3 to 5 in water) for high
enantioselectivity only delivered a comparable enantioselec-
tivity (50% ee) with that obtained in the absence of any
pyridine (45% ee). This latter fact excludes (or strongly
disfavors) a potential role of pyridine as a proton shuttle to
facilitate deprotonation of alcohol.[10c] The ligand role of
pyridine was further supported by its retarding effect on
reaction rate (Figure S3b, conducted at 108C), presumably by
stabilizing transient high-valent copper species.[9] Further-
more, the ee of products during reaction remained nearly
constant, supporting a uniform enantiodetermining transition
state along with the same reaction pathway for the reaction
(Figure S3c). Overall, the above results support that achiral
pyridine, at least primarily, acts as an ancillary ligand on
copper metal to greatly enhance the level of enantiocontrol.
On the basis of above mechanistic investigations and
previous studies,[4,5,12] a plausible catalytic cycle is tentatively
proposed (Scheme 2). At first, achiral pyridine is favorably
coordinated to CuI to form CuI-Py complex A. This complex
next reacts with CPA-activated Togniꢀs reagent by hydrogen
bonding[13] via single electron transfer, giving the crucial chiral
(LB)CuII phosphate complex B accompanied by the gener-
ation of CF3 radical. Subsequently, the addition of CF3 radical
to alkene gives a-CF3 alkyl radical C, which is trapped by B to
form a CuII species D. Subsequently a CuIII species E (path a)
may form.[4,5,9,14] In these two steps, the achiral pyridine-
coordinated copper complex and chiral phosphate counter-
anion work cooperatively to stabilize the reactive radical
intermediate and control the stereochemistry of this reaction.
Then, reductive elimination of E affords 3. However, the
other pathway via intramolecular single-electron oxidization
of intermediate D to the corresponding carbocation inter-
To gain some insight into the reaction mechanism, radical
trapping experiments were conducted by employing 2,2,6,6-
tetramethyl-1-piperidinyloxy and 1,4-benzoquinone, both of
which inhibited the reaction (Scheme S2a). Next, a radical
clock experiment with substrate 4 under the typical conditions
did not afford the expected product 5, while delivering 6 in
30% yield as a mixture of E/Z isomers, presumably via
a radical addition/cyclopropane ring opening/acid trapping
cascade process [Eq. (1)]. These observations, together with
previous studies,[4,5,12] suggest that CF3 radical is likely
generated in situ, which upon further addition to alkene
gives rise to a-CF3 alkyl radical C (Scheme 2). In addition,
only a trace amount of the desired product was obtained
either in the presence of a copper(II) salt or in the absence of
any copper catalysts (Scheme S2b). Furthermore, the reaction
did not work in the absence of phosphoric acid (Scheme S2b).
À
mediate F, which next undergoes C O bond formation to give
3, could not be excluded at the present stage (path b).
Alcohols are intrinsically less coordinative toward metal
than carboxylates and poorer hydrogen-bonding donors than
ureas, both of which render alcohols inapplicable in previ-
ously reported conditions.[4a,b,5] In this study, we have cap-
italized on a conceptually novel strategy with achiral pyridine
Scheme 2. Mechanistic proposal.
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

Angewandte
Communications
Chemie
Jacobsen, Angew. Chem. Int. Ed. 2013, 52, 534; Angew. Chem.
2013, 125, 558; d) D.-F. Chen, Z.-Y. Han, X.-L. Zhou, L.-Z.
Gong, Acc. Chem. Res. 2014, 47, 2365; e) Z.-P. Yang, W. Zhang,
S.-L. You, J. Org. Chem. 2014, 79, 7785; f) D. Parmar, E. Sugiono,
S. Raja, M. Rueping, Chem. Rev. 2014, 114, 9047; g) T. James, M.
van Gemmeren, B. List, Chem. Rev. 2015, 115, 9388; h) T.
Akiyama, K. Mori, Chem. Rev. 2015, 115, 9277.
as the ancillary ligand to achieve the first asymmetric radical
oxytrifluoromethylation of alkenes with alcohols. This trans-
formation offers a unique and direct approach to a wide range
of trifluoromethyl-substituted tetrahydrofurans bearing an a-
tertiary stereocenter with excellent efficiency, remarkable
enantioselectivity, good substrate scope and excellent func-
tional group tolerance. In addition, a series of mechanistic
experiments suggest that achiral pyridine may act as a coor-
dinative ligand on copper metal to stabilize the loosely
alcohol-binded transient Cu/CPA complexes, thus playing an
unusually significant role in asymmetric induction.
[7] A. Lorente, J. Lamariano-Merketegi, F. Albericio, M. ꢂlvarez,
Chem. Rev. 2013, 113, 4567.
[8] For reviews, see: a) J. P. Wolfe, M. B. Hay, Tetrahedron 2007, 63,
261; b) G. Jalce, X. Franck, B. Figadꢃre, Tetrahedron: Asymmetry
2009, 20, 2537; c) L. F. Tietze, K. M. Sommer, J. Zinngrebe, F.
Stecker, Angew. Chem. Int. Ed. 2005, 44, 257; Angew. Chem.
2005, 117, 262; d) K. H. Jensen, J. D. Webb, M. S. Sigman, J. Am.
Chem. Soc. 2010, 132, 17471; e) Y. Miller, L. Miao, A. S.
Hosseini, S. R. Chemler, J. Am. Chem. Soc. 2012, 134, 12149;
f) M. T. Bovino, T. W. Liwosz, N. E. Kendel, Y. Miller, N.
Tyminska, E. Zurek, S. R. Chemler, Angew. Chem. Int. Ed.
2014, 53, 6383; Angew. Chem. 2014, 126, 6501; g) B. A. Hopkins,
Z. J. Garlets, J. P. Wolfe, Angew. Chem. Int. Ed. 2015, 54, 13390;
Angew. Chem. 2015, 127, 13588; h) W. Zi, F. D. Toste, Angew.
Chem. Int. Ed. 2015, 54, 14447; Angew. Chem. 2015, 127, 14655.
[9] For a representative review of high-valent copper in catalysis, see:
a) A. J. Hickman, M. S. Sanford, Nature 2012, 484, 177; for
representative examples, see: b) S. H. Bertz, G. Miao, M.
Eriksson, Chem. Commun. 1996, 815; c) A. Alexakis, J. Vastra,
P. Mangeney, Tetrahedron Lett. 1997, 38, 7745; d) S. H. Bertz, S.
Cope, M. Murphy, C. A. Ogle, B. J. Taylor, J. Am. Chem. Soc.
2007, 129, 7208; e) E. R. Bartholomew, S. H. Bertz, S. Cope, D. C.
Dorton, M. Murphy, C. A. Ogle, Chem. Commun. 2008, 1176.
[10] For previous reports on the promoting effect of pyridine on
enantioselectivity as a ligand, see: a) E. M. Vogl, H. Grçger, M.
Shibasaki, Angew. Chem. Int. Ed. 1999, 38, 1570; Angew. Chem.
1999, 111, 1672; b) P. J. Walsh, A. E. Lurain, J. Balsells, Chem.
Rev. 2003, 103, 3297; c) L. Hong, W. Sun, D. Yang, G. Li, R.
Wang, Chem. Rev. 2016, 116, 4006, and references therein.
[11] CCDC 1536059 (S3V) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[12] For selected examples of racemic reactions, see: a) Y. Li, A.
Studer, Angew. Chem. Int. Ed. 2012, 51, 8221; Angew. Chem.
2012, 124, 8345; b) R. Zhu, S. L. Buchwald, J. Am. Chem. Soc.
2012, 134, 12462; c) Z. He, R. Zhang, M. Hu, L. Li, C. Ni, J. Hu,
Chem. Sci. 2013, 4, 3478; d) X.-Y. Jiang, F.-L. Qing, Angew.
Chem. Int. Ed. 2013, 52, 14177; Angew. Chem. 2013, 125, 14427;
e) N.-Y. Yang, Z.-L. Li, L. Ye, B. Tan, X.-Y. Liu, Chem.
Commun. 2016, 52, 9052.
Acknowledgements
Financial support from the National Natural Science Foun-
dation of China (No. 21572096), and Shenzhen overseas high
level talents innovation plan of technical innovation project
(KQCX20150331101823702) is greatly appreciated.
Conflict of interest
The authors declare no conflict of interest.
Keywords: achiral ligands · alkene oxytrifluoromethylation ·
asymmetric catalysis · copper · radical reactions
[1] For selected recent reviews, see: a) J. Nie, H.-C. Guo, D. Cahard,
J.-A. Ma, Chem. Rev. 2011, 111, 455; b) T. Furuya, A. S. Kamlet,
T. Ritter, Nature 2011, 473, 470; c) X. Yang, T. Wu, R. J. Phipps,
F. D. Toste, Chem. Rev. 2015, 115, 826; d) X.-H. Xu, K.
Matsuzaki, N. Shibata, Chem. Rev. 2015, 115, 731; e) C. Ni, M.
Hu, J. Hu, Chem. Rev. 2015, 115, 765.
[2] For selected recent reviews, see: a) T. Liang, C. N. Neumann, T.
Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214; Angew. Chem.
2013, 125, 8372; b) N. Zhang, S. R. Samanta, B. M. Rosen, V.
Percec, Chem. Rev. 2014, 114, 5848; c) L. Chu, F.-L. Qing, Acc.
Chem. Res. 2014, 47, 1513; d) E. Merino, C. Nevado, Chem. Soc.
Rev. 2014, 43, 6598; e) J. Charpentier, N. Frꢁh, A. Togni, Chem.
Rev. 2015, 115, 650; f) A. Studer, D. P. Curran, Angew. Chem. Int.
Ed. 2016, 55, 58; Angew. Chem. 2016, 128, 58; g) Y. Zeng, C. Ni,
J. Hu, Chem. Eur. J. 2016, 22, 3210.
[13] For examples reporting activation of Togniꢀs reagent by
Brønsted acid, see: a) P. Yu, J.-S. Lin, L. Li, S.-C. Zheng, Y.-P.
Xiong, L.-J. Zhao, B. Tan, X.-Y. Liu, Angew. Chem. Int. Ed. 2014,
53, 11890; Angew. Chem. 2014, 126, 12084; b) K. Niedermann, N.
Frꢁh, E. Vinogradova, M. S. Wiehn, A. Moreno, A. Togni,
Angew. Chem. Int. Ed. 2011, 50, 1059; Angew. Chem. 2011, 123,
1091.
[3] For reviews on asymmetric radical reactions, see: a) M. P. Sibi, S.
Manyem, J. Zimmerman, Chem. Rev. 2003, 103, 3263; b) L.
Zhang, E. Meggers, Acc. Chem. Res. 2017, 50, 320.
[14] For selected references on CuIII species and reactions involving
CuIII intermediates, see: a) L. M. Huffman, S. S. Stahl, J. Am.
Chem. Soc. 2008, 130, 9196; b) B. Zhao, X. Peng, S. Cui, Y. Shi, J.
Am. Chem. Soc. 2010, 132, 11009; c) Z.-L. Wang, L. Zhao, M.-X.
Wang, Chem. Commun. 2012, 48, 9418; d) S. E. Creutz, K. J.
Lotito, G. C. Fu, J. C. Peters, Science 2012, 338, 647; e) Y. Ye,
M. S. Sanford, J. Am. Chem. Soc. 2012, 134, 9034; f) A. J.
Walkinshaw, W. Xu, M. G. Suero, M. J. Gaunt, J. Am. Chem. Soc.
2013, 135, 12532.
[4] a) R. Zhu, S. L. Buchwald, Angew. Chem. Int. Ed. 2013, 52,
12655; Angew. Chem. 2013, 125, 12887; b) R. Zhu, S. L.
Buchwald, J. Am. Chem. Soc. 2015, 137, 8069; c) F. Wang, D.
Wang, X. Wan, L. Wu, P. Chen, G. Liu, J. Am. Chem. Soc. 2016,
138, 15547; d) D. Wang, F. Wang, P. Chen, Z. Lin, G. Liu, Angew.
Chem. Int. Ed. 2017, 56, 2054; Angew. Chem. 2017, 129, 2086;
e) L. Wu, F. Wang, X. Wan, D. Wang, P. Chen, G. Liu, J. Am.
Chem. Soc. 2017, 139, 2904.
[5] J.-S. Lin, X.-Y. Dong, T.-T. Li, N.-C. Jiang, B. Tan, X.-Y. Liu, J.
Am. Chem. Soc. 2016, 138, 9357.
[6] For selected reviews on process involving chiral anions or anion
recognition, see: a) R. J. Phipps, G. L. Hamilton, F. D. Toste, Nat.
Chem. 2012, 4, 603; b) M. Mahlau, B. List, Angew. Chem. Int. Ed.
2013, 52, 518; Angew. Chem. 2013, 125, 540; c) K. Brak, E. N.
Manuscript received: March 21, 2017
Revised: April 21, 2017
Final Article published: && &&, &&&&
4
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Asymmetric Catalysis
Y.-F. Cheng, X.-Y. Dong, Q.-S. Gu, Z.-L. Yu,
X.-Y. Liu*
&&&& — &&&&
Achiral Pyridine Ligand-Enabled
Enantioselective Radical
Oxytrifluoromethylation of Alkenes with
Alcohols
Magic pyridine: Achiral pyridine has been
shown to be crucial for accomplishing the
first asymmetric radical oxytrifluorome-
thylation of unactivated alkenes with
alcohols. The remarkably enhanced
enantioselectivity observed has been
accounted for by a stabilizing effect of
pyridine on high-valent copper inter-
mediates as an ancillary ligand.
Angew. Chem. Int. Ed. 2017, 56, 1 – 5
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!