Condensed-phase, halogen-bonded CF3I and C2F5I adducts for perfluoroalkylation reactions

Article abstract of DOI:10.1002/anie.201410954

A family of practical, liquid trifluoromethylation and pentafluoroethylation reagents is described. We show how halogen bonding can be used to obtain easily handled liquid reagents from gaseous CF₃I and CF₃CF₂I. The synthetic utility of the new reagents is exemplified by a novel direct arene trifluoromethylation reaction as well as adaptations of other perfluoroalkylation reactions. Its (no longer) a gas! A family of practical, liquid trifluoromethylation and pentafluoroethylation reagents enabled by halogen bonding is described. The synthetic utility of these reagents is exemplified by a novel direct arene trifluoromethylation reaction as well as adaptations of other perfluoroalkylation reactions.

Full text of DOI:10.1002/anie.201410954

Angewandte
Chemie
DOI: 10.1002/anie.201410954
Perfluoroalkylations
Condensed-Phase, Halogen-Bonded CF3I and C2F5I Adducts for
Perfluoroalkylation Reactions**
Filippo Sladojevich, Eric McNeill, Jonas Bçrgel, Shao-Liang Zheng, and Tobias Ritter*
Abstract: A family of practical, liquid trifluoromethylation
and pentafluoroethylation reagents is described. We show how
halogen bonding can be used to obtain easily handled liquid
reagents from gaseous CF3I and CF3CF2I. The synthetic utility
of the new reagents is exemplified by a novel direct arene
trifluoromethylation reaction as well as adaptations of other
perfluoroalkylation reactions.
gen bonding. Trifluoromethyl iodide is a common trifluoro-
methylation reagent.[8–14] Despite its utility and low cost ($ 110
per mol from Oakwood Products), routine use by synthetic
chemists has been challenging due to its boiling point of
À22.58C. The handling process is impractical, time consum-
ing, and imprecise in the measurements of small quantities,
when compared to the other more conveniently handled
reagents mentioned above.
F
luorinated organic molecules are increasingly useful in
We have found that CF3I and tetramethylguanidine
(TMG) form a 1:1 adduct that is liquid at 238C and can be
dispensed accurately with a syringe (Figure 1). A 30 g batch of
TMG·CF3I stored in a glass vial with a Teflon seal at 08C
medicinal chemistry, agrochemistry, and materials science.
Many recent advances in fluoroorganic chemistry[1] are due to
the development of safer, less toxic, or more selective
reagents. Examples in perfluoroalkylation include the Rup-
pert–Prakash reagent (Me3SiCF3),[2] the Trifluoromethylator
reagent (“CF3Cu”),[3] the Langlois reagent (CF3SO2Na),[4] the
Baran reagent Zn(SO2CF3)2,[5] the Umemoto reagent (S-
(trifluoromethyl)dibenzothiophenium),[6] and the Togni
reagents.[7] Perfluoroalkyl iodides, in particular CF3I,[8–14] are
useful and inexpensive sources of perfluoroalkyl frag-
ments.[1b,d,15] However, CF3I and C2F5I are gases, making
accurate measurement cumbersome. Stock solutions of CF3I
cannot be stored without quick decline of the titer (see the
Supporting Information). Here we introduce liquid-phase,
halogen-bonded adducts of CF3I and C2F5I as perfluoroalky-
lation reagents. The reagents are stable at room temperature
and can be conveniently manipulated. To the best of our
knowledge, our report describes the first application of
halogen bonding for organic reagent preparation, and the
first X-ray crystal structure of a halogen-bonded CF3I adduct.
Using the easily manipulated halogen-bonded adducts, we
Figure 1. Formation of liquid TMG·CF3I adduct via halogen bonding
between CF3I and tetramethylguanidine (TMG).
showed no signs of decomposition, loss in content of CF3I, or
pressure build-up over two months. This reagent is now
commercially available.[20] In addition to TMG, other Lewis
bases can be used. Notably, the non-Brønsted-basic DMSO
forms a 1:1 adduct with CF3I. The presence of a second
equivalent of DMSO imparts improved stability, making the
preferred formulation 2DMSO·CF3I. Like CF3I, C2F5I is a gas
in most laboratory settings (bp 12–138C) and forms a readily
handled liquid adduct with TMG. We found that
TMG·CF3CF2I and DMSO·CF3CF2I can be used in analogy
to TMG·CF3I and DMSO·CF3I as pentafluoroethylation
reagents.
À
have developed a novel direct arene C H trifluoromethyla-
tion reaction. We also show the applicability of our new
reagents as drop-in replacements for gaseous CF3I and C2F5I.
Halogen bonding[16] has been known since 1863[17] and has
found use in molecular recognition and supramolecular
chemistry.[18] However, halogen bonding has received rela-
tively little attention from synthetic organic chemists[9c,17j,19]
compared to other non-covalent interactions such as hydro-
[*] Dr. F. Sladojevich, Dr. E. McNeill, J. Bçrgel, Dr. S.-L. Zheng,
Prof. Dr. T. Ritter
Trifluoromethylated arenes are increasingly common
structural motifs in pharmaceuticals and agrochemicals.[21]
Historically, trifluoromethyl arenes were synthesized via the
Swarts reaction[22] or cross-coupling.[1e,15i,23] An attractive
Department of Chemistry and Chemical Biology
Harvard University
12 Oxford St., Cambridge, MA 02138 (USA)
E-mail: ritter@chemistry.harvard.edu
Homepage: http://rittergroup.org
À
alternative to these methods is direct C H trifluoromethyla-
tion by trifluoromethyl radical. Reagents such as CF3SO2
À
[**] We thank Gregory B. Boursalian (Harvard) for X-ray data collection,
the European Community (Marie Curie IOF fellowship to F.S.), and
the NSF (CHE-0952753) for financial support.
salts,[4,5] gaseous CF3I,[8] CF3SO2Cl,[24a] (CF3)SiMe3,[24b–d] and
Togniꢀs reagent[24e] have been used for this transformation.
Some current methodologies are limited to specific substrate
classes such as heterocycles, phenols, or anilines. Others
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201410954.
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require the use of reagents that are gaseous or corrosive, or
require special apparatus to perform. We have developed
generally modest; generation of mixtures of positional
isomers is common for direct arene trifluoromethyla-
tions.[4,5,8,24] Direct arene trifluoromethylation using
TMG·CF3I is an effective and operationally simple method
made possible by the condensed-phase nature of the reagent.
To further demonstrate the synthetic utility of TMG·CF3I,
we have explored its use as a drop-in replacement for gaseous
CF3I (Scheme 1). TMG·CF3I can be used in Stephensonꢀs
À
a method for C H trifluoromethylation that does not suffer
from these limitations.
Utilizing liquid TMG·CF3I, we were able to rapidly
optimize conditions for direct arene trifluoromethylation.
We found that electron-neutral to electron-rich arenes could
be directly trifluoromethylated when treated with TMG·CF3I,
K2S2O8, and Cu(OAc)2·H2O in acetic acid at 908C
(Table 1).[25] The reactions are conducted under ambient
atmosphere and with no need for rigorous exclusion of
moisture or specialized equipment.
The reaction conditions are compatible with common
arene substituents, including ethers, esters, nitriles, and
amides. The reaction is also effective with highly substituted
arenes and electron-deficient heterocycles. The reagent
TMG·CF3CF2I can be substituted for TMG·CF3I to afford
pentafluoroethylated products. Positional selectivities are
Table 1: Direct perfluoroalkylation of arenes using halogen-bonded
reagents.[a]
Scheme 1. Representative perfluoroalkylation reactions using halogen-
bonded reagents. [Ru]=[Ru(bipy)3]Cl2·6H2O. TDAE=tetrakis(dimethyl-
amino)ethylene.
photoredox-catalyzed oxidative olefin trifluoromethylation
(Scheme 1A).[9b,e] Likewise, thiol trifluoromethylation can be
accomplished with TMG·CF3I (Scheme 1B). In both cases,
TMG acts as a base in addition to providing a liquid source of
CF3I.
In other cases, we found the presence of TMG to be
detrimental. For example, TMG·CF3I was not a suitable CF3I
surrogate for the MacMillan trifluoromethylation of enol
ethers
under
photoredox
catalysis.[11h]
However,
2DMSO·CF3I proved effective both in the MacMillan
trifluoromethylation and in the TDAE-mediated trifluoro-
methyl addition to aldehydes (Scheme 1C and D, respec-
tively). The ability of tetramethylguanidine to serve as one-
electron reductant and/or H-atom donor may explain the
differing reactivity of DMSO·CF3I and TMG·CF3I. We have
also found that TMG·CF3CF2I is effective for pentafluoro-
ethylation (Scheme 1E and F).
[a] Conditions: 2 equiv TMG·CF3I, 4 equiv K2S2O8, 2 equiv Cu(OAc)2·
H2O, AcOH, 908C, 24 h. Yields of isolated products are shown unless
otherwise specified. * indicates site of minor functionalization. [b] Yield
determined by 19F NMR spectroscopy. [c] Reaction conducted at 1208C.
[d] 4 equiv tBuOOH and 0.2 equiv FeSO4·7H2O were utilized instead of
K2S2O8 and Cu(OAc)2·H2O. [e] TMG·CF3CF2I was utilized instead of
TMG·CF3I.
2
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To better understand our new reagents, we investigated
the bonding in greater detail. The 1:1 stoichiometry of
TMG·CF3I was established by integration of the 1H and
19F NMR signals against a 1-fluoro-3-nitrobenzene standard.
When approximately 5 equivalents of CF3I were condensed
into a known amount of TMG at À238C, and the reaction
mixture was warmed to 238C, CF3I evaporated until a 1:1
liquid adduct (TMG·CF3I) was formed. The experiment is
consistent with a well-defined 1:1 adduct.
We were unable to characterize TMG·CF3I by X-ray
crystallography, but we obtained crystals of the TMEDA
analog (Figure 2A). While the TMEDA·2CF3I adduct
behaves similarly to the TMG·CF3I adduct (see the Support-
ing Information), the TMEDA-based crystalline solid became
sticky with storage, making it less practical to handle than
TMG·CF3I. The iodine–nitrogen interaction, which we
ascribe to halogen bonding, was unambiguously established
by measuring an interatomic N···I distance of 2.80 ꢁ, smaller
than the sum of the van der Waals radii for N and I (3.53 ꢁ).
DFT calculations corroborated the experimentally deter-
mined N···I distance. With the validated DFT functionals, we
found an N···I distance of 2.8 ꢁ for TMG·CF3I, and an
interaction energy corrected for basis set superposition error
(BSSE) of 9–10 kcalmolÀ1, near the upper end of the 1–
10 kcalmolÀ1 range for halogen bond strength.[18j] The calcu-
lated halogen bond strength is consistent with the temper-
ature and storage stability of TMG·CF3I.
Halogen bonding can be rationalized as a non-covalent
polar interaction between halogen bond donors, such as CF3I,
and halogen bond acceptors, such as TMG.[18h,i] The three
filled lone pairs on iodine are almost purely s- and p-based
À
orbitals, with little hybridization (Figure 2C); the C I s-bond
has pz character on iodine, and is polarized toward the
electron-withdrawing CF3 group. Thus, minimal electron
density is observed in the outermost region of the iodine
À
atom along the z axis of the C I s-bond; this region has been
named the s-hole[26] (Figure 2D). The attractive interaction
between a Lewis base such as TMG and the s-hole contrib-
utes to halogen bonding.[18h,i]
In conclusion, we have described the first use of halogen
bonding to access reagents for organic synthesis. Stable,
readily handled liquid adducts of CF3I and CF3CF2I were
prepared and used in perfluoroalkylation reactions. Using
Figure 2. A) X-ray structure of TMEDA·2CF3I; experimentally measured
and calculated N···I distance; calculated interaction energy per CF3I
molecule. B) Calculated interaction energy and N···I distance for
TMG·CF3I. C) The two p-type and the s-type iodine lone pairs in CF3I.
D) Electrostatic potential map of CF3I (in Hartrees) at the 0.001 elec-
tronsBohrÀ3 isodensity surface highlighting the s-hole region. See the
Supporting Information for details on the DFT calculations.
À
TMG·CF3I, a novel arene C H trifluoromethylation reaction
has been developed. Given the strong interest in fluoro-
organic compounds and perfluoroalkylation reagents, we
anticipate that our reagents will be of use to the community
both in wider accessibility of the rich chemistry of CF3I and in
development of novel reactions.
concentrated in vacuo. The residue was purified by chromatography
on silica gel.
Received: November 11, 2014
Published online: && &&, &&&&
À
Experimental Section
Keywords: arenes · C H functionalization · halogen bonding ·
pentafluoroethylation · trifluoromethylation
.
General procedure for direct trifluoromethylation of arenes: Arene
(0.250 mmol, 1.00 equiv), K2S2O8 (270 mg, 1.00 mmol, 4.00 equiv),
and Cu(OAc)2·H2O (100 mg, 0.500 mmol) were dissolved in glacial
acetic acid (2.0 mL). TMG·CF3I (0.100 mL, 0.500 mmol, 2.00 equiv)
was added, the reaction vessel was sealed and heated to 908C for 24 h.
The reaction mixture was diluted with saturated aqueous Na2CO3
(50 mL) and the resulting mixture extracted with ethyl acetate (3 ꢂ
25 mL). The combined ethyl acetate extracts were dried (MgSO4) and
[1] a) Modern Fluoroorganic Chemistry (Ed.: P. Kirsch), Wiley-
VCH, Weinheim, 2004; b) T. Furuya, A. S. Kamlet, T. Ritter,
Nature 2011, 473, 470 – 477; c) C. Hollingworth, V. Gouverneur,
Chem. Commun. 2012, 48, 2929 – 2942; d) Z. Jin, G. B. Ham-
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
mond, B. Xu, Aldrichimica Acta 2012, 45, 67 – 83; e) T. Liang,
C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214 –
8264; Angew. Chem. 2013, 125, 8372 – 8423; f) M. G. Campbell,
T. Ritter, Org. Process Res. Dev. 2014, 18, 474 – 480.
[12] Boronic acids: Y. Ye, M. S. Sanford, J. Am. Chem. Soc. 2012, 134,
9034 – 9037.
[13] Aryl iodides: a) Y. Kobayashi, I. Kumadaki, Tetrahedron Lett.
1969, 10, 4095 – 4096; b) Y. Kobayashi, I. Kumadaki, S. Sato, N.
Hara, E. Chikami, Chem. Pharm. Bull. 1970, 18, 2334 – 2339; c) I.
Kumadaki, M. Hirai„ M. Koyama, T. Nagai, A. Ando, T. Miki,
Synth. Commun. 1989, 19, 173 – 177.
[14] Aldehydes: a) T. Kitazume, N. Ishikawa, J. Am. Chem. Soc. 1985,
107, 5186 – 5191; b) S. Aꢄt-Mohand, N. Takechi, M. Medebielle,
W. R. Dolbier, Jr., Org. Lett. 2001, 3, 4271 – 4273; c) C. Pooput,
W. R. Dolbier, Jr., M. Medebielle, J. Org. Chem. 2006, 71, 3564 –
3568; d) M. Fujiu, Y. Nakamura, H. Serizawa, K. Aikawa, S. Ito,
K. Mikami, Eur. J. Org. Chem. 2012, 7043 – 7047.
[2] a) I. Ruppert, K. Schlich, W. Volbach, Tetrahedron Lett. 1984, 25,
2195 – 2198; b) G. K. S. Prakash, R. Krishnamurti, G. A. Olah, J.
Am. Chem. Soc. 1989, 111, 393 – 395; c) G. K. S. Prakash, A. K.
Yudin, Chem. Rev. 1997, 97, 757 – 786.
[3] H. Morimoto, T. Tsubogo, N. D. Litvinas, J. F. Hartwig, Angew.
Chem. Int. Ed. 2011, 50, 3793 – 3798; Angew. Chem. 2011, 123,
3877 – 3882.
[4] B. R. Langlois, E. Laurent, N. Roidot, Tetrahedron Lett. 1991, 32,
7525 – 7528.
[15] a) R. P. Singh, J. M. Shreeve, Tetrahedron 2000, 56, 7613 – 7632;
b) G. K. S. Prakash, M. Mandal, J. Fluorine Chem. 2001, 112,
123 – 131; c) J.-A. Ma, D. Cahard, Chem. Rev. 2004, 104, 6119 –
6146; d) K. L. Kirk, Org. Process Res. Dev. 2008, 12, 305 – 321;
e) R. J. Lundgren, M. Stradiotto, Angew. Chem. Int. Ed. 2010, 49,
9322 – 9324; Angew. Chem. 2010, 122, 9510 – 9512; f) K. Sato, A.
Tarui, M. Omote, A. Ando, I. Kumadaki, Synthesis 2010, 1865 –
1882; g) T. Besset, C. Schneider, D. Cahard, Angew. Chem. Int.
Ed. 2012, 51, 5048 – 5050; Angew. Chem. 2012, 124, 5134 – 5136;
h) Y. Macꢅ, E. Magnier, Eur. J. Org. Chem. 2012, 2479 – 2494;
i) O. A. Tomashenko, V. V. Grushin, Chem. Rev. 2011, 111,
4475 – 4521; j) A. Studer, Angew. Chem. Int. Ed. 2012, 51, 8950 –
8958; Angew. Chem. 2012, 124, 9082 – 9090; k) X.-F. Wu, H.
Neumann, M. Beller, Chem. Asian J. 2012, 7, 1744 – 1754.
[16] G. R. Desiraju, P. S. Ho, L. Kloo, A. C. Legon, R. Marquardt, P.
Metrangolo, P. Politzer, G. Resnati, K. Rissanen, Pure Appl.
Chem. 2013, 85, 1711 – 1713.
[5] a) Y. Ji, T. Brueckl, R. D. Baxter, Y. Fujiwara, I. B. Seiple, S. Su,
D. G. Blackmond, P. S. Baran, Proc. Natl. Acad. Sci. USA 2011,
108, 14411 – 14415; b) Y. Fujiwara, J. A. Dixon, F. OꢀHara, E. D.
Funder, D. D. Dixon, R. A. Rodriguez, R. D. Baxter, B. Herle, N.
Sach, M. R. Collins, Y. Ishihara, P. S. Baran, Nature 2012, 492,
95 – 99; c) F. OꢀHara, R. D. Baxter, A. G. OꢀBrien, M. R. Collins,
J. A. Dixon, Y. Fujiwara, Y. Ishihara, P. S. Baran, Nat. Protoc.
2013, 8, 1042 – 1047; d) F. OꢀHara, D. G. Blackmond, P. S. Baran,
J. Am. Chem. Soc. 2013, 135, 12122 – 12134; e) A. G. OꢀBrien, A.
Maruyama, Y. Inokuma, M. Fujita, P. S. Baran, D. G. Black-
mond, Angew. Chem. Int. Ed. 2014, DOI: 10.1002/
anie.201407948; Angew. Chem. 2014, DOI: 10.1002/
ange.201407948.
[6] a) T. Umemoto, S. Ishihara, K. Adachi, J. Fluorine Chem. 1995,
74, 77 – 82; b) T. Umemoto, Chem. Rev. 1996, 96, 1757 – 1777;
c) T. Umemoto, K. Adachi, S. Ishihara, J. Org. Chem. 2007, 72,
6905 – 6917.
[17] F. Guthrie, J. Chem. Soc. Trans. 1863, 16, 239 – 244.
[18] a) P. Metrangolo, G. Resnati, Chem. Eur. J. 2001, 7, 2511 – 2519;
b) P. Metrangolo, H. Neukirch, T. Pilati, G. Resnati, Acc. Chem.
Res. 2005, 38, 386 – 395; c) K. Rissanen, CrystEngComm 2008,
10, 1107 – 1113; d) P. Metrangolo, F. Meyer, T. Pilati, G. Resnati,
G. Terraneo, Angew. Chem. Int. Ed. 2008, 47, 6114 – 6127;
Angew. Chem. 2008, 120, 6206 – 6220; e) R. Bertani, P. Sgar-
bossa, A. Venzo, F. Lelj, M. Amati, G. Resnati, T. Pilati, P.
Metrangolo, G. Terraneo, Coord. Chem. Rev. 2010, 254, 677 –
695; f) G. Cavallo, P. Metrangolo, T. Pilati, G. Resnati, M.
Sansotera, G. Terraneo, Chem. Soc. Rev. 2010, 39, 3772 – 3783;
g) M. Erdꢅlyi, Chem. Soc. Rev. 2012, 41, 3547 – 3557; h) P.
Politzer, J. S. Murray, T. Clark, Phys. Chem. Chem. Phys. 2010,
12, 7748 – 7757; i) P. Politzer, J. S. Murray, T. Clark, Phys. Chem.
Chem. Phys. 2013, 15, 11178 – 11189; j) T. M. Beale, M. G.
Chudzinski, M. G. Sarwar, M. S. Taylor, Chem. Soc. Rev. 2013,
42, 1667 – 1680.
[19] a) A. Bruckmann, M. A. Pena, C. Bolm, Synlett 2008, 900 – 902;
b) S. M. Walter, F. Kniep, E. Herdtweck, S. M. Huber, Angew.
Chem. Int. Ed. 2011, 50, 7187 – 7191; Angew. Chem. 2011, 123,
7325 – 7329; c) F. Kniep, S. H. Jungbauer, Q. Zhang, S. M.
Walter, S. Schindler, I. Schnapperelle, E. Herdtweck, S. M.
Huber, Angew. Chem. Int. Ed. 2013, 52, 7028 – 7032; Angew.
Chem. 2013, 125, 7166 – 7170; d) F. Meyer, P. Dubois, CrystEng-
Comm 2013, 15, 3058 – 3071; e) R. Wilcken, M. O. Zimmermann,
A. Lange, A. C. Joerger, F. M. Boeckler, J. Med. Chem. 2013, 56,
1363 – 1388.
[7] a) P. Eisenberger, I. Kieltsch, R. Koller, K. Stanek, A. Togni,
Org. Synth. 2011, 88, 168 – 180; b) V. Matousek, E. Pietrasiak, R.
Schwenk, A. Togni, J. Org. Chem. 2013, 78, 6763 – 6768.
[8] (Hetero)arenes: a) A. B. Cowell, C. Tamborski, J. Fluorine
Chem. 1981, 17, 345 – 356; b) T. Kino, Y. Nagase, Y. Ohtsuka,
K. Yamamoto, D. Uraguchi, K. Tokuhisa, T. Yamakawa, J.
Fluorine Chem. 2010, 131, 98 – 105; c) R. N. Loy, M. S. Sanford,
Org. Lett. 2011, 13, 2548 – 2551; d) N. Iqbal, S. Choi, E. Ko, E. J.
Cho, Tetrahedron Lett. 2012, 53, 2005.
[9] Olefins: a) Y. Takeyama, Y. Ichinose, K. Oshima, K. Utimoto,
Tetrahedron Lett. 1989, 30, 3159 – 3162; b) J. D. Nguyen, J. W.
Tucker, M. D. Konieczynska, C. R. J. Stephenson, J. Am. Chem.
Soc. 2011, 133, 4160 – 4163; c) S. Dordonne, B. Crousse, D.
Bonnet-Delpon, J. Legros, Chem. Commun. 2011, 47, 5855 –
5857; d) N. Iqbal, S. Choi, E. Kim, E. J. Cho, J. Org. Chem.
2012, 77, 11383 – 11387; e) C.-J. Wallentin, J. D. Nguyen, P.
Finkbeiner, C. R. J. Stephenson, J. Am. Chem. Soc. 2012, 134,
8875 – 8884.
[10] Thiols: a) M. E. Houston, Jr., J. F. Honek, J. Chem. Soc. Chem.
Commun. 1989, 761 – 762; b) V. G. Koshechko, L. A. Kipria-
nova, L. I. Fileleeva, Tetrahedron Lett. 1992, 33, 6677 – 6678;
c) V. N. Boiko, G. M. Shchupak, J. Fluorine Chem. 1994, 69, 207 –
212; d) A. Harsꢃnyi, E. Dorko, A. Csapo, T. Bako, C. Peltz, J.
Rabai, J. Fluorine Chem. 2011, 132, 1241 – 1246.
[11] Enolates: a) K. Iseki, T. Nagai, Y. Kobayashi, Tetrahedron Lett.
1993, 34, 2169 – 2170; b) Y. Itoh, K. Mikami, Org. Lett. 2005, 7,
649 – 651; c) Y. Itoh, K. Mikami, Org. Lett. 2005, 7, 4883 – 4885;
d) Y. Itoh, K. Mikami, Tetrahedron 2006, 62, 7199 – 7203; e) V.
Petrik, D. Cahard, Tetrahedron Lett. 2007, 48, 3327 – 3330;
f) D. A. Nagib, M. E. Scott, D. W. C. MacMillan, J. Am. Chem.
Soc. 2009, 131, 10875 – 10877; g) K. Sato, T. Yuki, R. Yamaguchi,
T. Hamano, A. Tarui, M. Omote, I. Kumadaki, A. Ando, J. Org.
Chem. 2009, 74, 3815 – 3819; h) P. V. Pham, D. A. Nagib, D. W. C.
MacMillan, Angew. Chem. Int. Ed. 2011, 50, 6119 – 6122; Angew.
Chem. 2011, 123, 6243 – 6246; i) A. T. Herrmann, L. L. Smith, A.
Zakarian, J. Am. Chem. Soc. 2012, 134, 6976 – 6979.
[20] TMG·CF3I:
Sigma–Aldrich
catalog
number
794473;
2DMSO·CF3I: Sigma–Aldrich catalog number 794503;
TMG·CF3CF2I: Sigma–Aldrich catalog number 794465;
DMSO·CF3CF2I: Sigma–Aldrich catalog number 794481.
[21] W. K. Hagmann, J. Med. Chem. 2008, 51, 4359.
[22] L. M. Yagupolskii in Houben-Weyl: Methods of Organic
Chemistry, Vol. E10a (Eds.: B. Baasner, H. Hagemann, J.-C.
Tatlow), Thieme, Stuttgart, 2000, pp. 509 – 534.
[23] a) A. Lishchynskyi, M. A. Novikov, E. Martin, E. C. Escudero-
Adꢃn, P. Novꢃk, V. V. Grushin, J. Org. Chem. 2013, 78, 11126 –
4
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Chemie
11146; b) M. G. Mormino, P. S. Fier, J. F. Hartwig, Org. Lett.
2014, 16, 1744 – 1747.
[25] CuII salts may aid rearomatization: A. Bravo, H.-R. Bjørsvik, F.
Fontana, L. Liguori, A. Mele, F. Minisci, J. Org. Chem. 1997, 62,
[24] a) D. A. Nagib, D. W. C. MacMillan, Nature 2011, 480, 224; b) Y.
Ye, S. H. Lee, M. S. Sanford, Org. Lett. 2011, 13, 5464; c) S. Seo,
J. B. Taylor, M. F. Greaney, Chem. Commun. 2013, 49, 6385;
d) T. Nishida, H. Ida, Y. Kuninobu, M. Kanai, Nat. Commun.
2014, 5, 3387; e) E. Mejꢆa, A. Togni, ACS Catal. 2012, 2, 521.
7128.
[26] T. Clark, M. Hennemann, J. S. Murray, P. Politzer, J. Mol. Model.
2007, 13, 291 – 296.
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Perfluoroalkylations
It’s (no longer) a gas! A family of
practical, liquid trifluoromethylation and
pentafluoroethylation reagents enabled
by halogen bonding is described. The
synthetic utility of these reagents is
exemplified by a novel direct arene tri-
fluoromethylation reaction as well as
adaptations of other perfluoroalkylation
reactions.
F. Sladojevich, E. McNeill, J. Bçrgel,
S.-L. Zheng, T. Ritter*
&&& — &&&
Condensed-Phase, Halogen-Bonded CF3I
and C2F5I Adducts for Perfluoroalkylation
Reactions
6
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!