Silver-Mediated Oxidative Trifluoromethylation of Alcohols to Alkyl Trifluoromethyl Ethers

Article abstract of DOI:10.1021/acs.orglett.5b02522

The development of an efficient and practical method for the preparation of alkyl trifluoromethyl ethers is urgently demanding. The silver-mediated oxidative O-trifluoromethylation of primary, secondary, and tertiary alcohols with TMSCF₃ under mild reaction conditions is established to provide a novel approach to a broad range of alkyl trifluoromethyl ethers. Further, this method is applied to the late-stage O-trifluoromethylation of complex natural products and prescribed pharmaceutical agents.

Full text of DOI:10.1021/acs.orglett.5b02522

Letter
pubs.acs.org/OrgLett
Silver-Mediated Oxidative Trifluoromethylation of Alcohols to Alkyl
Trifluoromethyl Ethers
Jian-Bo Liu,† Xiu-Hua Xu,† and Feng-Ling Qing*,†,‡
†Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling
Lu, Shanghai 200032, China
‡College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai 201620,
China
S
* Supporting Information
ABSTRACT: The development of an efficient and practical method for the
preparation of alkyl trifluoromethyl ethers is urgently demanding. The silver-
mediated oxidative O-trifluoromethylation of primary, secondary, and tertiary
alcohols with TMSCF3 under mild reaction conditions is established to
provide a novel approach to a broad range of alkyl trifluoromethyl ethers.
Further, this method is applied to the late-stage O-trifluoromethylation of complex natural products and prescribed
pharmaceutical agents.
xtensive recent efforts have been devoted to the preparation
dibenzofuranium reagents gave the corresponding alkyl tri-
Eof fluorinated compounds because the introduction of fluoromethyl ethers.8a However, these highly active O-(trifluoro-
1
methyl)dibenzofuranium reagents need to be generated prior to
use by photochemical decomposition of diazonium salts
containing a trifluoromethoxy group at −100 to −90 °C.
Togni and co-workers have developed the Zn(NTf2)2-mediated
synthesis of alkyl trfluoromethyl ethers from alcohols and
electrophilic hypervalent iodine trifluoromethylation reagent,8b
but the use of alcohols as both the substrate and solvent was
necessary to obtain good yields of alkyl trfluoromethyl ethers.
Thus, the development of a practical and broadly applicable
trifluoromethylation of alcohols for synthesis of alkyl trfluor-
omethyl ethers is still highly desirable.
Recently, we have developed the transition-metal-mediated
oxidative trifluoromethylation of various nucleophiles with
nucleophilic TMSCF3 in the presence of oxidants, and these
methods allow novel and efficient construction of C(sp,sp2,sp3)−
CF3, P−CF3, and S−CF3 bonds.9 We wondered if it was possible
to achieve the analogous reaction of alcohols with TMSCF3 to
form an O−CF3 bond (Scheme 1). This transformation is more
fluorine atom and fluorine-containing group into organic
compounds often changes the chemical, physical, and biological
properties of parent compounds.2 Among the fluorinated
moieties, the trifluoromethoxy group (OCF3) is strongly
electron withdrawing and offers advantages such as increased
lipophilicity over the popular F and CF3 group.3 Therefore, this
group offers increasingly important functionality in materials,
agricultural, and pharmaceutical research.4 Significant progress
has been made toward the incorporation of a fluorine atom,
trifluoromethyl group, and trifluoromethylthio group onto
aromatic and aliphatic systems.1 However, methodologies for
the general and efficient synthesis of alkyl trifluoromethyl ethers
are extremely underdeveloped and limited.
There are mainly three types of methods for the preparation of
alkyl trifluoromethyl ethers. The deoxyfluorination of alkyl
fluoroformates5 and oxidative desulfurization−fluorination of
alkyl xanthates6 are the most widely used procedures, but the
harsh reaction conditions employed in these reactions are
incompatible with many functional groups. The nucleophilic
trifluoromethoxylation of alkyl triflates and bromides with
trifluoromethoxide salts provides an alternative route to alkyl
trifluoromethyl ethers.7 However, the reversible degradation of
trifluoromethoxide into carbonyl difluoride and fluoride in
solution above room temperature hinders widespread adoption.
Clearly, the direct trifluoromethylation of alcohols under mild
reaction conditions would be an ideal route to alkyl
trifluoromethyl ethers due to the abundance and accessibility
of alcohols.8 In fact, the formation of an O−CF3 bond from
alcohol with a trifluormethylating reagent is difficult because the
oxygen atom, a hard nucleophile, is disfavored to react with the
electrophilic trifluoromethlating reagents. Umemoto and co-
workers reported that the direct electrophilic trifluoromethyla-
tion of 2-phenylethanol and n-decanol with O-(trifluoromethyl)-
Scheme 1. Synthesis of Alkyl Trifluoromethyl Ethers via
Oxidative Trifluoromethylation of alcohols
challenging than other oxidative trifluoromethylation reactions
because alkanols are sensitive toward the oxidation conditions10
and metal alkoxide intermediates might undergo competitive β-
hydride elimination.11 We assumed that these competitive
reactions could be eliminated or reduced by choosing the
appropriate metal salt, ligand, and oxidant. Herein, we disclose
Received: September 2, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02522
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the AgOTf-mediated oxidative trifluoromethylation of alcohols
with TMSCF3 at room temperature to alkyl trifluoromethyl
ethers. Not only primary alcohols but also secondary and tertiary
alcohols were compatible in this protocol. The late-stage O-
trifluoromethylation of complex natural products and prescribed
pharmaceutical agents is also exhibited.
7 and 8). Both 2-fluoropyridine and 3-fluoropyridine were
superior to pyridine (entries 9 and 10), and 2-fluoropyridine was
the optimal choice probably because of its comparatively lower
basicity.13 Switching to other oxidants such as air, BzOO-t-Bu,
and N-fluorobenzenesulfonimide (NFSI) could not produce 4a
(entries 11−13). To further improve the yield of 4a, we decided
to increase the amounts of AgOTf, 2-fluoropyridine, Selecfluor,
TMSCF3, and KF. The high selective formation of 4a was
achieved when 2.0 equiv of AgOTf and 2-fluoropyridine were
used (entry 14), while the use of 1.5 equiv of Selectfluor resulted
in higher conversion of 1a (entry 15). Finally, the conversion of
1a reached up to 96%, and the yield of 4a was improved to 81%
(entry 16) in the presence of AgOTf (3.0 equiv), 2-
fluoropyridine (3.0 equiv), Selectfluor (1.5 equiv), TMSCF3
(3.0 equiv), and KF (4.0 equiv).
Initially, we chose 1-(4-fluorophenyl)ethan-1-ol (1a) as the
model substrate to optimize the reaction conditions (Table 1).
Table 1. Optimization of Oxidative Trifluoromethylation of
a
Alcohol 1a with TMSCF3
b
b
conv
(%)
yield (%)
With the optimized reaction conditions in hand, we next
investigated the substrate scope of this silver-mediated oxidative
trifluoromethylation of alcohols (Scheme 2). Various primary,
secondary, and tertiary alcohols were converted to the
corresponding trifluoromethyl ethers in moderate to excellent
entry
1
[M]
ligand
pyridine
oxidant
2a/3a/4a
AgNO3
Selectfluor
55 55/
−/trace
2
3
4
5
6
7
8
Cu(OTf)2 pyridine
Pd(OAc)2 pyridine
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
35 35/−/−
91 83/−/−
Ni(OTf)2
AgOTf
pyridine
pyridine
pyridine
PPh3
9
9/−/−
Scheme 2. Substrate Scope of Silver-Mediated
47 42/−/5
−/−/−
20 20/−/−
a
Trifluoromethylation of Alkanols
Ag2CO3
AgOTf
AgOTf
Phen
50 50/
−/trace
9
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
2-
Selectfluor
Selectfluor
air
49 23/−/26
44 24/−/20
24 18/6/−
fluoropyridine
10
11
12
13
3-
fluoropyridine
2-
fluoropyridine
2-
BzOO-t-Bu
NFSI
33 18/8/−
fluoropyridine
2-
> 99 >99/−/−
54 13/−/41
80 22/−/58
96 12/−/81
fluoropyridine
c
14
2-
Selectfluor
Selectfluor
Selectfluor
fluoropyridine
c,d
15
2-
fluoropyridine
d,e
16
2-
fluoropyridine
a
Reaction conditions: 1a (0.1 mmol), TMSCF3 (0.2 mmol), KF (0.3
mmol), oxidant (0.1 mmol), [M] (0.1 mmol), ligand (0.1 mmol),
b
EtOAc (0.5 mL), rt, 12 h. Determined by 19F NMR spectroscopy
c
using trifluoromethylbenzene as an internal standard. AgOTf (0.2
d
mmol), 2-fluoropyridine (0.2 mmol). Selectfluor (0.15 mmol).
e
TMSCF3 (0.3 mmol), KF (0.4 mmol), AgOTf (0.3 mmol), 2-
fluoropyridine (0.3 mmol).
This substrate contains an aryl fluorine moiety, which is
beneficial for tracing the reaction by 19F NMR spectroscopy.
Inspired by our very recent work on silver-mediated oxidative
trifluoromethylation of phenols for synthesis of aryl trifluor-
omethyl ethers,12 we attempted the trifluoromethylation of 1a
with TMSCF3 in the presence of silver salt (AgNO3), ligand
(pyridine), and oxidant (Selectfluor) (entry 1). Unfortunately,
only a trace amount of the desired product 4a was observed, and
ketone 2a was formed as the major product. Other metal salts
including Cu(OTf)2, Pd(OAc)2, and Ni(OTf)2 also led to the
formation of 2a (entries 2−4). To our delight, compound 4a was
produced in 5% yield in the presence of AgOTf (entry 5), while
there was no reaction when Ag2CO3 was used instead of AgOTf
(entry 6). Then, different ligands were investigated. Neither
PPh3 nor 1,10-phenanthroline (phen) gave better results (entries
a
b
Isolated yields. TMSCF3 (2.0 equiv), KF (3.0 equiv), AgOTf (2.0
c
equiv), 2-fluoropyridine (2.0 equiv). 2,6-Di-tert-butylphenol (0.5
equiv) was added. Selectfluor (1.0 equiv).
d
B
DOI: 10.1021/acs.orglett.5b02522
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
yields. For primary alcohols, lower amounts of TMSCF3 (2.0
equiv), KF (3.0 equiv), AgOTf (2.0 equiv), and 2-fluoropyridine
(2.0 equiv) could achieve high yields. A variety of functional
groups, including benzyloxy, carbonyl, ester, amide, cyano, nitro,
chloro, bromo, and iodo, are well tolerated under this mild
reaction conditions. The reaction efficiency of alcohols
containing the electron-rich aryl group (such as 1j) was
diminished by the competitive C-trifluoromethyaltion of
electron-rich phenyl ring with eletrophilic CF3 radical, because
CF3 radical was easily generated from the combination of
TMSCF3/KF/AgOTf.14 To our delight, the C-competitive
trifluoromethylation was sharply reduced by the addition of
2,6-di-tert-butylphenol. In the case of benzyl alcohols (1l, 1m, 1p,
and 1q) bearing the electron-withdrawing group on the phenyl
ring, the corresponding benzaldehydes were formed as the major
products under the standard reaction conditions (1.5 equiv of
selecfluor). Fortunately, the desired trifluoromethyl ethers were
obtained in moderate yields when 1.0 equiv of Selecfluor was
used. It is noteworthy that the dr value of product 4z (2.7:1) was
almost the same as that of compound 1z (2.6:1). This result
showed that the configuration of alcohols was fully retained in
this oxidative trifluoromethylation reaction.
Scheme 3. Late-Stage O-Trifluoromethylation of Natural
Product Derivatives and Bioactive Compounds
a
To further extend the application of this protocol, a series of
natural product derivatives and bioactive compounds was also
investigated (Scheme 3). The protected L-serine (1ad), L-
theronine (1ae), and D-glucopyranose (1af) were compatible
with the reaction conditions to afford the corresponding
trifluoromethyl ethers in moderate yields. This protocol allowed
the direct trifluoromethylation of steroids epitestosterone (1ag)
and dihydrocholesterol (1ah). Importantly, the reaction of
idebenone (1ai), a drug for the treatment of Alzheimer’s disease,
gave product 4ai in 64% yield. Several hormones including
epiandrosterone (1aj), estradiol benzoate (1ak), and cortisone
(1al) proceeded well to give the corresponding trifluoromethyl
ethers (4aj−al) in good to excellent yields. Moreover, the
alcohols derived from rosuvastatin (a member of the drug class of
statins) and ezetimibe (a drug that lowers plasma cholesterol
levels), respectively, were converted to the trifluoromethylated
products 4am and 4an. These results showed that this protocol
was applicable to the late-stage trifluoromethylation of
medicinally relevant compounds.
a
b
Isolated yields. TMSCF3 (2.0 equiv), KF (3.0 equiv), AgOTf (2.0
c
equiv), 2-fluoropyridine (2.0 equiv). 2,6-Di-tert-butylphenol (0.5
equiv) was added.
Scheme 4. Mechanism Experiments
Several mechanism experiments were carried out to gain
insight of the reaction mechanism (see the Supporting
Information for details). All of the reactions outlined in Scheme
4 were monitored by 19F NMR spectroscopy. No reaction was
observed when 1a was treated with AgOTf, KF, and 2-
fluoropyridine (Scheme 4a). On the other hand, the reaction
of TMSCF3 and AgOTf, KF, and 2-fluoropyridine gave
15
Ag(I)CF3 in 50% yield along with Ag(III) complex [Ag-
16
(CF3)4]− in 6% yield (Scheme 4b). These results showed
clearly that the oxidative trifluoromethylation proceeded through
trifluoromethyl silver complex, not alkoxy silver complex.
Interestingly, Ag(I)CF3 could be converted into [Ag(CF3)4]−
and only [Ag(CF3)4]− could be detected after 2 h (Scheme 4c).
However, the reaction of [Ag(CF3)4]− with Selectfluor and 1a
did not give any trifluoromethyl ether 4a. In contrast, the
addition of 1a and Selectfluor to the mixture of Ag(I)CF3 and
[Ag(CF3)4]− afforded 4a in 12% yield (Scheme 4d). These
results demonstrated that Ag(I)CF3 was the really active
intermediate for the oxidative trifluoromethylation of alcohols.
On the basis of the above experimental results and the silver-
mediated oxidative cross-coupling reactions,12,17 a plausible
reaction mechanism was proposed in Scheme 5. First, TMSCF3
Scheme 5. Proposed Mechanism
C
DOI: 10.1021/acs.orglett.5b02522
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(4) (a) Shimizu, M.; Hiyama, T. Angew. Chem., Int. Ed. 2005, 44, 214.
(b) Leroux, F. R.; Jeschke, P.; Schlosser, M. Chem. Rev. 2005, 105, 827.
(c) Jeschke, P.; Baston, E.; Leroux, F. R. Mini-Rev. Med. Chem. 2007, 7,
1027. (d) Leroux, F. R.; Manteau, M.; Vors, J.; Pazenok, P. S. Beilstein J.
Org. Chem. 2008, 4, 13. (e) Rozen, S. Adv. Synth. Catal. 2010, 352, 2691.
(f) Manteau, B.; Pazenok, S.; Vors, J. P.; Leroux, F. R. J. Fluorine Chem.
2010, 131, 140. (g) Landelle, G.; Panossian, A.; Leroux, F. R. Curr. Top.
Med. Chem. 2014, 14, 941. (h) Campbell, M. G.; Ritter, T. Org. Process
Res. Dev. 2014, 18, 474. (i) Illendula, A.; Pulikkan, J. A.; Zong, H.;
Grembecka, J.; Xue, L.; Sen, S.; Zhou, Y.; Boulton, A.; Kuntimaddi, A.;
Gao, Y.; Rajewski, R. A.; Guzman, M. L.; Castilla, L. H.; Bushweller, J. H.
Science 2015, 347, 779.
was converted into Ag(I)CF3 in the presence of AgOTf, KF, and
2-fluoropyridine. Then, Ag(I)CF3 was oxidized by Selectfluor to
form Ag(III) complex A, which subsequently underwent ligand
exchange with alkoxide to give intermediate B. Finally, reductive
elimination of intermediate B afforded the desired alkyl
trifluomethyl ether (ROCF3).
In conclusion, we have developed an efficient and practical
method for the preparation of alkyl trifluoromethyl ethers using
silver-mediated oxidative trifluoromethylation of alcohols with
TMSCF3 at room temperature. Various primary, secondary, and
tertiary alcohols, especially a series of highly complex medicinal
molecules, proceeded efficiently under these mild reaction
conditions. Due to the potential utility of the resulting alkyl
trifluoromethyl ethers and the mild conditions employed, we
expect this method to be of broad utility in the pharmaceutical
and agrochemical fields.
(5) (a) Sheppard, W. A. J. Org. Chem. 1964, 29, 1. (b) Aldrich, P. E.;
Sheppard, W. A. J. Org. Chem. 1964, 29, 11.
(6) For selected examples, see: (a) Kuroboshi, M.; Kanie, K.; Hiyama,
T. Adv. Synth. Catal. 2001, 343, 235. (b) Blazejewski, J.-C.; Anselmi, E.;
Wakselman, C. J. Org. Chem. 2001, 66, 1061. (c) Carcenac, Y.; Tordeux,
M.; Wakselman, C.; Diter, P. New J. Chem. 2006, 30, 447. (d) Zriba, R.;
Magnier, E.; Blazejewski, J.-C. Synlett 2009, 2009, 1131. (e) Umemoto,
T.; Singh, R. P.; Xu, Y.; Saito, N. J. Am. Chem. Soc. 2010, 132, 18199.
(f) Umemoto, T.; Singh, R. P. J. Fluorine Chem. 2012, 140, 17.
(g) Zhang, H.-K.; Yu, L.-F.; Eaton, J. B.; Whiteaker, P.; Onajole, O. K.;
Hanania, T.; Brunner, D.; Lukas, R. J.; Kozikowski, A. P. J. Med. Chem.
2013, 56, 5495. (h) Inoue, T.; Fuse, C.; Hara, S. J. Fluorine Chem. 2015,
DOI: 10.1016/j.jfluchem.2015.04.016.
(7) (a) Kolomeitsev, A. A.; Vorobyev, M.; Gillandt, H. Tetrahedron
Lett. 2008, 49, 449. (b) Marrec, O.; Billard, T.; Vors, J.-P.; Pazenok, S.;
Langlois, B. R. Adv. Synth. Catal. 2010, 352, 2831. (c) Marrec, O.;
Billard, T.; Vors, J.-P.; Pazenok, S.; Langlois, B. R. J. Fluorine Chem.
2010, 131, 200. (d) Barbion, J.; Pazenok, S.; Vors, J.-P.; Langlois, B. R.;
Billard, T. Org. Process Res. Dev. 2014, 18, 1037. (e) Chen, S.; Huang, Y.;
Fang, X.; Li, H.; Zhang, Z.; Hor, T. S. A.; Weng, Z. Dalton Trans. 2015,
DOI: 10.1039/C5DT02078F.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b02522.
Preliminary investigation of reaction mechanism, exper-
imental procedures, characterization data, and copies of
1H, 19F, and 13C NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: flq@mail.sioc.ac.cn.
Notes
(8) (a) Umemoto, T.; Adachi, K.; Isihara, S. J. Org. Chem. 2007, 72,
6905. (b) Koller, R.; Stanek, K.; Stolz, D.; Aardoom, R.; Niedermann, K.;
Togni, A. Angew. Chem., Int. Ed. 2009, 48, 4332.
The authors declare no competing financial interest.
(9) (a) Chu, L.; Qing, F. L. J. Am. Chem. Soc. 2010, 132, 7262. (b) Chu,
L.; Qing, F. L. Org. Lett. 2010, 12, 5060. (c) Chu, L.; Qing, F. L. J. Am.
Chem. Soc. 2012, 134, 1298. (d) Wu, X.; Chu, L.; Qing, F. L. Angew.
Chem., Int. Ed. 2013, 52, 2198. (e) Chu, L.; Qing, F. L. Synthesis 2012,
44, 1521. (f) Chen, C.; Xie, Y.; Chu, L.; Wang, R. W.; Zhang, X.; Qing, F.
L. Angew. Chem., Int. Ed. 2012, 51, 2492. (g) Chu, L.; Qing, F. L. Acc.
Chem. Res. 2014, 47, 1513.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(21421002, 21332010, 21272036) and the National Basic
Research Program of China (2012CB21600) for funding this
work.
́
(10) (a) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chou, C. S.
REFERENCES
■
J. Am. Chem. Soc. 1984, 106, 3374. (b) Gamez, P.; Arends, I. W. C. E.;
Reedijk, J.; Sheldon, R. A. Chem. Commun. 2003, 2414. (c) Kumpulai-
nen, E. T. T.; Koskinen, A. M. P. Chem. - Eur. J. 2009, 15, 10901.
(d) Hoover, J. M.; Ryland, B. L.; Stahl, S. S. J. Am. Chem. Soc. 2013, 135,
2357.
(1) For selected reviews, see: (a) Tomashenko, O. A.; Grushin, V. V.
Chem. Rev. 2011, 111, 4475. (b) Liu, T.; Shen, Q. Eur. J. Org. Chem.
2012, 2012, 6679. (c) Ye, Y.; Sanford, M. Synlett 2012, 23, 2005.
(d) Chen, P.; Liu, G. Synthesis 2013, 45, 2919. (e) Liang, T.; Neumann,
C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214. (f) Wang, H.;
Vicic, D. A. Synlett 2013, 24, 1887. (g) Egami, H.; Sodeoka, M. Angew.
Chem., Int. Ed. 2014, 53, 8294. (h) Campbell, M. G.; Ritter, T. Chem.
Rev. 2015, 115, 612. (i) Charpentier, J.; Fruh, N.; Togni, A. Chem. Rev.
2015, 115, 650. (j) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015,
115, 683. (k) Xu, X. H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115,
731. (l) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765. (m) Yang, X.;
Wu, T.; Phipps, R. J.; Toste, F. D. Chem. Rev. 2015, 115, 826. (n) Alonso,
C.; Martinez de Marigorta, E.; Rubiales, G.; Palacis, F. Chem. Rev. 2015,
115, 1847.
(11) (a) Torraca, K. E.; Huang, X.; Parrish, C. A.; Buchwald, S. L. J. Am.
Chem. Soc. 2001, 123, 10770. (b) Gowrisankar, S.; Sergeev, A. G.;
Anbarasan, P.; Spannenberg, A.; Neumann, H.; Beller, M. J. Am. Chem.
Soc. 2010, 132, 11592. (c) Wu, X.; Fors, B. P.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2011, 50, 9943.
(12) Liu, J.-B.; Chen, C.; Chu, L.; Chen, Z.-H.; Xu, X.-H.; Qing, F.-L.
Angew. Chem., Int. Ed. 2015, 54, 11839.
(13) The pKa values of pyridine, 3-fluoropyridine, and 2-fluoropyridine
are 5.17, 2.97, and −0.44, respectively . Brown, H. C. In Determination of
Organic Structures by Physical Methods; Braude, E. A., Nachod, F. C.,
Eds.; Academic Press: New York, 1955.
(14) Ye, Y.; Lee, S. H.; Sanford, M. Org. Lett. 2011, 13, 5464.
(15) For a review about silver perfluoroalkyl complexes, see: Tyrra, W.
E.; Naumann, D. J. Fluorine Chem. 2004, 125, 823.
(16) Dukat, W.; Naumann, D. Rev. Chim. Miner. 1986, 23, 589.
(17) Huang, C.; Liang, T.; Harada, S.; Lee, E.; Ritter, T. J. Am. Chem.
Soc. 2011, 133, 13308.
(2) (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
̈
(b) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev.
2008, 37, 320. (c) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.
(d) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529. (e) Wang, J.;
Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.;
́
́
̃
Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432.
(f) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N.
A. J. Med. Chem. 2015, DOI: 10.1021/acs.jmedchem.5b00258.
(3) (a) Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Nikaitani, D.;
Lien, E. J. J. Med. Chem. 1973, 16, 1207. (b) Hansch, C.; Leo, A.; Taft, R.
W. Chem. Rev. 1991, 91, 165.
D
DOI: 10.1021/acs.orglett.5b02522
Org. Lett. XXXX, XXX, XXX−XXX