Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides

Article abstract of DOI:10.1002/anie.201800644

While acid fluorides can readily be made from widely available or biomass-feedstock-derived carboxylic acids, their use as functional groups in metal-catalyzed cross-coupling reactions is rare. This report presents the first demonstration of Pd-catalyzed

Full text of DOI:10.1002/anie.201800644

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Accepted Article
Title: Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid
Fluorides
Authors: Sinead Keaveney and Franziska Schoenebeck
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201800644
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10.1002/anie.201800644
Angewandte Chemie International Edition
DOI: 10.1002/anie.201??
Trifluoromethylation
Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid
Fluorides**
Sinead T. Keaveney and Franziska Schoenebeck*
Dedicated to Professor K. N. Houk on the occasion of his 75th birthday.
Abstract: While acid fluorides can readily be made from widely
available or biomass-feedstock derived carboxylic acids, their use
as functional groups in metal-catalyzed cross-coupling reactions
is rare. This report presents the first demonstration of Pd-
catalyzed decarbonylative functionalization of acid fluorides to
yield trifluoromethyl arenes (ArCF3). The strategy relies on a
Pd/Xantphos catalytic system and the supply of fluoride for
transmetalation via intramolecular redistribution to the Pd center.
This strategy eliminated the need for exogenous and detrimental
fluoride additives and allows Xantphos to be used in catalytic
trifluoromethylations for the first time. Our experimental and
computational mechanistic data support a sequence in which
transmetalation by R3SiCF3 occurs prior to decarbonylation.
pool for trifluoromethylation from aryl chlorides or bromides[9-10] to
underexplored and easily accessible aryl carboxylic acid derivatives,
i.e. acid fluorides.
Challenges in Pd(0)/Pd(II) catalyzed Trifluoromethylation of ArX
 Reductive Elimination
Few Effective Ligands
 Mechanism:
(only ArBr & ArCl)
-
-

Effective only stoichiometrically:
(trace moisture
sensitive)
(2 equiv. of F- salt needed )

Effective in catalysis:
 Challenge Transmetalation – Ligand Displacement
O
wing to their wide abundance, stability and relatively low cost,
carboxylic acids and their derivatives belong to some of the most
attractive functionalities for synthetic manipulations.[1] They are
featured in numerous natural products and are also key fragments
resulting from biomass valorization.[2] As such, strategies to
selectively convert carboxylic acids into value-added functional
groups are in high demand. In particular, the introduction of fluorine
into organic molecules has been recognized as a strategy to manipulate
properties, impacting pharmaceutical, agrochemical and materials
Our previous Work:
This Work:
. Decarbonylative trifluoromethylation
. Rapid & direct
. F for transmetalation delivered intramolecularly
. First catalytic effectiveness of Xantphos
. Wide array of functionality
. Filtration as purification
chemistry research.[3] In this context, the introduction of
a
trifluoromethyl group via Pd(0)/Pd(II) catalysis belongs to one of the
greatest challenges in the cross-coupling arena (see Figure 1). This is
due to several reasons, including the very difficult reductive
elimination of ArCF3 from the [LnPd(II)(Ar)(CF3)] intermediate.[4] This
challenging step has only been accomplished by a handful of ligands,
of which several, e.g. Xantphos[5] and dfmpe[6], are (so far) only
effective stoichiometrically, but not in catalysis. This is due to the
propensity of the transmetalating “CF3 anions” to displace these
weaker coordinating ligands.[4e, 5c, 7] Moreover, several equivalents of
fluoride salt additive are generally required to activate the
transmetalating agent, such as R3SiCF3, and even the smallest ppm
Figure 1. Overview of challenges in Pd(0)/Pd(II) catalyzed trifluoromethylation (top)
and our work (bottom).
We envisioned that
a decarbonylation/trifluoromethylation
strategy utilizing carboxylic acid derivatives could circumvent some
of the most severe challenges in Pd(0)/Pd(II) catalyzed
trifluoromethylations. If we were able to react acid fluorides with a
Pd(0) source a Pd(II)-F intermediate would be directly generated (Figure
1), which is the only Pd(II) intermediate that can be transmetalated
directly without the need for an external fluoride additive.[5c] Thus, the
liberation of reactive “CF3” anions, which are detrimental to many
metal/ligand combinations, would be avoided.[4e, 5c, 7a] Encouragingly,
acid fluorides have previously been coupled to the corresponding
ketones under metal catalysis, as pioneered by Rovis.[11] However,
while the decarbonylation of carboxylic acids and their derivatives[1m,
(including acid chlorides[13]) has been widely studied, to date,
there has been no report of a successful decarbonylation of acid
fluorides.
Our group recently reported a facile and direct synthesis of acid
fluorides from carboxylic acids,[14] allowing us to investigate whether
a decarbonylation/functionalization protocol could be developed for a
wide array of acid fluorides.
quantities of moisture introduced by these salts can cause catalyst
8]
decomposition.[4e,
As such, Buchwald’s catalytic Pd(0)/Pd(II)
catalyzed trifluoromethylation of aryl chlorides is
a major
accomplishment.[9] We report herein our studies to widen the precursor
[]
Dr. Sinead T. Keaveney, Prof. Dr. Franziska Schoenebeck
Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen, Germany
1o, 12]
E-mail: franziska.schoenebeck@rwth-aachen.de
Homepage: http://www.schoenebeck.oc.rwth-aachen.de/
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201xxxxxx.
1
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10.1002/anie.201800644
Angewandte Chemie International Edition
We started our investigations with the biaryl acid fluoride 1a,
utilizing Xantphos as the ligand for Pd. Although Xantphos[15] has
never been effective in catalytic trifluoromethylations, it is one of the
few ligands capable of facilitating reductive elimination from
[LnPd(II)(Ar)(CF3)].[5b, 5c] To our delight 15% of the desired product
ArCF3 2a (see Table 1) was formed in our initial investigations
employing TMSCF3 as transmetalating agent. These data indicated
that Xantphos is capable of promoting both the decarbonylation and
ArCF3 reductive elimination steps without the need for exogenous
fluoride. Further examination of the reaction conditions (see SI)
revealed that the highest yield of 2a was obtained with TESCF3 and a
catalytic amount of K3PO4.[1b, 16] When we applied the same reaction
conditions to the analogous ArCl and ArBr substrates, the
trifluoromethylated products were not generated, indicating that the
acid fluoride moiety is key.
These reactivity features make this a complimentary method to
Buchwald’s procedure with ArCl.[9] While 2-phenylbenzoyl fluoride
1b gave 82% conversion to the desired ArCF3 product 2b with our
protocol, the corresponding 2-phenyl aryl chloride generated much
less of 2b with Buchwald’s method in our tests (BrettPhos: <5%
conversion, RuPhos: 34% conversion).
To investigate whether sequential functionalization of carboxylic
acids would be possible, we subjected a handful of exemplary
substrates (Table 2) to the bench-stable salt (Me4N)SCF3 in DCM,[14]
followed by Pd-catalyzed decarbonylation/trifluoromethylation. This
allowed for efficient conversion of carboxylic acids to ArCF3 over two
steps in good overall yields.
Table 2. The two-step conversion of carboxylic acids 3 to ArCF3 2.
With the successful conditions in hand, we subsequently examined
the generality of the method (Table 1). We successfully converted a
range of acid fluorides into the corresponding ArCF3 compounds, with
ether, alkyl and fluorine containing substituents being tolerated.
Notably, the acid fluoride derivative of 3,4-dimethoxybenzoic acid
(1h), which is the end-product from Lignin valorization,[17] was also
successful. The highest yields were obtained for those substrates that
possessed otho-substitution to the COF functionality,[18] in line with
reactivity trends previously seen for metal-catalyzed decarbonylations
19]
of other carbonyl derivatives,[1j,
or trifluoromethylations.[20] For
example, the slight modification from para- to ortho-linkage of the
biphenyl acid fluoride 1a (to 1b) resulted in a two-fold increase in
yield.
Conditions: 3 (0.4 mmol), (Me4N)SCF3 (77 mg, 0.44 mmol) in DCM (2 mL), then:
the resulting ArCOF 1, [(cinnamyl)PdCl]2 (8 mg, 0.016 mmol), Xantphos (28 mg,
0.048 mmol), K3PO4 (17 mg, 0.08 mmol), TESCF3 (160 μL, 0.8 mmol) in toluene
(1.2 mL). Isolated yields are shown (conversion in parentheses as determined by
19F NMR spectroscopic analysis against internal standard). aReaction performed
at 180 °C.
Table 1. Scope of the decarbonylative trifluoromethylation.
We next investigated the mechanism of the transformation.[21]
Following the oxidative addition of the acid fluoride to Pd(0), the
corresponding Pd(II) intermediate could in principle undergo
decarbonylation, followed by transmetalation with R3SiCF3
(Mechanism A, Figure 2). Alternatively, the Pd(II) intermediate could
be transmetalated prior to CO loss to give the CF3-bound Pd(II)CO
analogue, which could then decarbonylate (Mechanism B). In both
cases, a Pd(II)-F intermediate would be present which would be very
prone to transmetalation. We computationally[22] assessed these
possibilities with CPCM (toluene) M06L/def2TZVP//ωB97XD/6-
31G(d)+SDD level of theory at 160°C and using phenyl acid fluoride
as model substrate.[23] Our data suggest that oxidative addition of the
phenyl acid fluoride is relatively facile, proceeding with a barrier of
∆G‡ = 10.1 kcal mol-1. As such, the acid fluoride appears to be a
promising alternative to acid chlorides, which have been widely used
in catalysis but are also much less robust than their fluorinated
counterparts.[13]
Decarbonylation from the PhCO-[Pd(II)]-F intermediate is
predicted to have a free energy barrier of ∆G‡ = 27.3 kcal mol-1.
Interestingly, the alternative of decarbonylating the already
transmetalated complex, i.e. PhCO-[Pd(II)]-CF3, is computed to have a
much lower activation free energy barrier of only ∆G‡ = 17.4 kcal mol-
1. These data indicate that decarbonylation becomes more facile when
moving from the F to CF3 ligated complex. A distortion/ interaction
analysis[24] of the barriers for decarbonylation from both PhCO-
[Pd(II)]-F and PhCO-[Pd(II)]-CF3 reveal that the lower barrier for
decarbonylation from PhCO-[Pd(II)]-CF3 arises from the transition
Conditions: 1 (0.4 mmol), [(cinnamyl)PdCl]2 (8 mg, 0.016 mmol), Xantphos (28 mg,
0.048 mmol), K3PO4 (17 mg, 0.08 mmol), TESCF3 (160 μL, 0.8 mmol) in toluene
(1.2 mL). Isolated yields are shown (conversion in parentheses as determined by
19F NMR spectroscopic analysis against internal standard). aReaction performed
at 180 °C. bSpecies 2g was not isolated due its volatility.
2
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10.1002/anie.201800644
Angewandte Chemie International Edition
state having a more favourable Pd – Xantphos interaction as well as a
slightly lower distortion energy, relative to the transition state for
decarbonylation from PhCO-[Pd(II)]-F (see SI for details).[25]
Scheme 1. Temperature dependent ArCF3 2a versus ArCOCF3 4a formation.
ΔG‡ = 17.4
Decarbonylation TS B
ΔG‡ = 10.1
oxidative addition
In conclusion, the first decarbonylative functionalization of acid
fluorides to ArCF3 compounds was showcased. The strategy relies on
the intramolecular supply of the crucial fluoride for transmetalation,
allowing Xantphos to be effective in catalytic trifluoromethylations for
the first time, as exogenous fluoride and detrimental over-
transmetalation could be avoided. Our computational and experi-
mental reactivity data support a mechanism that involves first
transmetalation, followed by decarbonylation. Given that Pd(II)-F is a
key intermediate for selective and additive-free transmetalations to
introduce a range of functionalities (with CF3 being the most
challenging), this work sets the stage to convert carboxylic acids to a
wide array of compounds via the vital acid fluoride intermediate.
ΔG‡ = 27.3
Decarbonylation
TSA
Via:
Decarbonylation TS A
Decarbonylation TS B
vs.
ΔG‡ = 27.3
ΔG‡ = 17.4
Acknowledgements
Figure 2. Mechanistic possibilities for ArCOF to ArCF3 conversion (top) and
computed activation free energy barriers at the CPCM (toluene) M06L/ def2TZVP//
ωB97XD/6-31G(d)+SDD level of theory at 160°C [ΔG‡ given in kcal mol-1]. Bottom:
illustration of computed decarbonylation transition states.
We thank Indrek Kalvet (RWTH Aachen University) for discussions
and assistance with calculations. We thank the RWTH Aachen
University, the MIWF NRW, and the European Research Council
(ERC-637993) for funding. Calculations were performed with
computing resources granted by JARA-HPC from RWTH Aachen
University under project ‘jara0091’
Considering that transmetalation between R3SiCF3 and Pd(II)-F has
experimentally been shown to occur “within the time of mixing”,[5c]
and that decarbonylation from PhCO-[Pd(II)]-CF3 is more facile than
that from PhCO-[Pd(II)]-F, Mechanism B appears to be favored for the
conversion of ArCOF to ArCF3.
In Mechanism B there is the choice to either decarbonylate and
proceed productively towards ArCF3 from the intermediate complex
ArCO-[Pd(II)]-CF3, or instead to reductively eliminate directly to the
corresponding ketone ArCOCF3 4 (see Scheme 1). Experimentally we
observed a strong temperature dependence of the overall product
selectivity (see Scheme 1): reacting biphenyl acid fluoride 1a at 145 °C
under otherwise identical catalysis conditions resulted in a significant
portion of biphenyl-4-trifluoromethyl ketone 4a being formed (32%)
along with the product resulting from CO-loss, i.e. ArCF3 2a (in 28%).
A systematic increase of the reaction temperature led to much less of
the ketone 4a being formed (4% at 160°C and 0% at 180°C), yielding
ArCF3 2a as exclusive product at 180°C (43% at 160°C and 46% at
180°C).[26] Given that higher temperature will impact the entropic
contributions in the activation free energy barrier, it appears
reasonable that more decarbonylation (to ultimately form ArCF3) takes
place. Computationally, these trends are qualitatively reflected. We
calculate an activation free energy difference (ΔΔG‡) of 1.0 kcal mol-
1 at 25°C and 1.5 kcal mol-1 at 160°C for the competing pathways of
ketone formation versus decarbonylation for substrate 1a, with
preference for decarbonylation in each case.
Keywords: trifluoromethylation • catalysis • palladium • DFT •
carboxylic acids
[1] For selected recent examples on decarbonylative and decarboxylative
cross couplings, see: a) C. Li, J. Wang, L. M. Barton, S. Yu, M. Tian,
D. S. Peters, M. Kumar, A. W. Yu, K. A. Johnson, A. K. Chatterjee, M.
Yan, P. S. Baran, Science 2017, 356, eaam7355; b) R. Takise, R. Isshiki,
K. Muto, K. Itami, J. Yamaguchi, J. Am. Chem. Soc. 2017, 139, 3340; c)
L. Guo, A. Chatupheeraphat, M. Rueping, Angew. Chem. Int. Ed. 2016,
55, 11810; d) S. Shi, G. Meng, M. Szostak, Angew. Chem. Int. Ed. 2016,
55, 6959; e) A. N. Desnoyer, F. W. Friese, W. Chiu, M. W. Drover, B.
O. Patrick, J. A. Love, Chem. Eur. J. 2016, 22, 4070; f) Z. Zuo, D. T.
Ahneman, L. Chu, J. A. Terrett, A. G. Doyle, D. W. C. MacMillan,
Science 2014, 345, 437; g) A. Correa, J. Cornella, R. Martin, Angew.
Chem. Int. Ed. 2013, 52, 1878; h) J. Cornella, H. Lahlali, I. Larrosa,
Chem. Commun. 2010, 46, 8276; i) D. V. Gribkov, S. J. Pastine, M.
Schnürch, D. Sames, J. Am. Chem. Soc. 2007, 129, 11750; j) L. J.
Gooßen, G. Deng, L. M. Levy, Science 2006, 313, 662; k) T. Sugihara,
T. Satoh, M. Miura, M. Nomura, Angew. Chem. Int. Ed. 2003, 42, 4672;
l) L. J. Gooßen, J. Paetzold, Angew. Chem. Int. Ed. 2002, 41, 1237. For
reviews, see: m) T. Patra, D. Maiti, Chem. Eur. J. 2017, 23, 7382; n) R.
Takise, K. Muto, J. Yamaguchi, Chem. Soc. Rev. 2017, 46, 5864; o) N.
Rodriguez, L. J. Goossen, Chem. Soc. Rev. 2011, 40, 5030; p) L. J.
3
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10.1002/anie.201800644
Angewandte Chemie International Edition
Gooßen, N. Rodríguez, K. Gooßen, Angew. Chem. Int. Ed. 2008, 47,
3100.
[2] a) R. A. Sheldon, Green Chem. 2014, 16, 950; b) D. R. Dodds, R. A.
Gross, Science 2007, 318, 1250.
[13] a) C. A. Malapit, N. Ichiishi, M. S. Sanford, Org. Lett. 2017, 19, 4142;
b) X. Zhao, Z. Yu, J. Am. Chem. Soc. 2008, 130, 8136; c) T. Sugihara,
T. Satoh, M. Miura, Tetrahedron Lett. 2005, 46, 8269; d) Y. Obora, Y.
Tsuji, T. Kawamura, J. Am. Chem. Soc. 1993, 115, 10414.
[3] a) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly, N. A. Meanwell,
J. Med. Chem. 2015, 58, 8315; b) P. A. Champagne, J. Desroches, J.-D.
Hamel, M. Vandamme, J.-F. Paquin, Chem. Rev. 2015, 115, 9073; c) T.
Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214;
d) G. Landelle, A. Panossian, S. Pazenok, J.-P. Vors, F. R. Leroux,
Beilstein Journal of Organic Chemistry 2013, 9, 2476; e) R. Berger, G.
Resnati, P. Metrangolo, E. Weber, J. Hulliger, Chem. Soc. Rev. 2011, 40,
3496; f) L. E. Zimmer, C. Sparr, R. Gilmour, Angew. Chem. Int. Ed.
2011, 50, 11860; g) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur,
Chem. Soc. Rev. 2008, 37, 320; h) K. Müller, C. Faeh, F. Diederich,
Science 2007, 317, 1881; i) G. Theodoridis, in Advances in Fluorine
Science, Vol. Volume 2 (Ed.: T. Alain), Elsevier, 2006, pp. 121.
[4] a) J. del Pozo, E. Gioria, P. Espinet, Organometallics 2017, 36, 2884; b)
M. A. García-Monforte, S. Martínez-Salvador, B. Menjón, European
Journal of Inorganic Chemistry 2012, 2012, 4945; c) O. A. Tomashenko,
V. V. Grushin, Chem. Rev. 2011, 111, 4475; d) G. G. Dubinina, W. W.
Brennessel, J. L. Miller, D. A. Vicic, Organometallics 2008, 27, 3933;
e) V. V. Grushin, W. J. Marshall, J. Am. Chem. Soc. 2006, 128, 4632; f)
D. A. Culkin, J. F. Hartwig, Organometallics 2004, 23, 3398. An
alternative approach is to oxidize Pd(II) to Pd(IV), as these complexes are
more prone to reductive elimination, see: g) N. D. Ball, J. B. Gary, Y.
Ye, M. S. Sanford, J. Am. Chem. Soc. 2011, 133, 7577; h) N. D. Ball, J.
W. Kampf, M. S. Sanford, J. Am. Chem. Soc. 2010, 132, 2878.
[5] a) V. I. Bakhmutov, F. Bozoglian, K. Gómez, G. González, V. V.
Grushin, S. A. Macgregor, E. Martin, F. M. Miloserdov, M. A. Novikov,
J. A. Panetier, L. V. Romashov, Organometallics 2012, 31, 1315; b) P.
Anstaett, F. Schoenebeck, Chem. Eur. J. 2011, 17, 12340; c) V. V.
Grushin, W. J. Marshall, J. Am. Chem. Soc. 2006, 128, 12644.
[6] M. C. Nielsen, K. J. Bonney, F. Schoenebeck, Angew. Chem. Int. Ed.
2014, 53, 5903.
[7] a) D. Naumann, N. V. Kirij, N. Maggiarosa, W. Tyrra, Y. L.
Yagupolskii, M. S. Wickleder, Z. Anorg. Allg. Chem. 2004, 630, 746. An
alpha-fluoride elimination side-reaction has recently been proposed in
the reductive elimination of ArCF3 from PtBu3-derived Pd(II) complexes:
b) D. M. Ferguson, J. R. Bour, A. J. Canty, J. W. Kampf, M. S. Sanford,
J. Am. Chem. Soc. 2017, 139, 11662.
[8] W. Tyrra, M. M. Kremlev, D. Naumann, H. Scherer, H. Schmidt, B.
Hoge, I. Pantenburg, Y. L. Yagupolskii, Chem. Eur. J. 2005, 11, 6514.
[9] E. J. Cho, T. D. Senecal, T. Kinzel, Y. Zhang, D. A. Watson, S. L.
Buchwald, Science 2010, 328, 1679.
[10] B. S. Samant, G. W. Kabalka, Chem. Commun. 2011, 47, 7236.
[11] a) A. Boreux, K. Indukuri, F. Gagosz, O. Riant, ACS Catalysis 2017, 7,
8200; b) Y. Ogiwara, D. Sakino, Y. Sakurai, N. Sakai, Eur. J. Org.
Chem. 2017, 2017, 4324; c) Y. Zhang, T. Rovis, J. Am. Chem. Soc. 2004,
126, 15964.
[14] T. Scattolin, K. Deckers, F. Schoenebeck, Org. Lett. 2017, 19, 5740.
[15] Xantphos has been utilized in Pd-catalyzed decarbonylations of aliphatic
esters (A. John, B. Dereli, M. A. Ortuño, H. E. Johnson, M. A. Hillmyer,
C. J. Cramer, W. B. Tolman, Organometallics 2017, 36, 2956) and
acetate salts (R. Shang, D.-S. Ji, L. Chu, Y. Fu, L. Liu, Angew. Chem.
Int. Ed. 2011, 50, 4470), there are no reported decarbonylations of
aromatic species.
[16] While the effect of the catalytic K3PO4 was not investigated herein, we
speculate that K3PO4 activates TESCF3 for transmetalation or,
alternatively, promotes decarbonylation. For precedence of lewis bases
activating TESCF3, see: a) G. P. Stahly, D. R. Bell, J. Org. Chem. 1989,
54, 2873; b) Liu, C. Xu, M. Wang, Q. Liu, Chem. Rev. 2015, 115, 683.
For precedence of bases favoring decarbonylation, see: c) T. Hattori, R.
Takakura, T. Ichikawa, Y. Sawama, Y. Monguchi, H. Sajiki, J. Org.
Chem. 2016, 81, 2737; d) Akanksha, D. Maiti, Green Chem. 2012, 14,
2314; and ref. 1b).
[17] For recent studies on lignin valorisation see: a) X. Ren, P. Wang, X. Han,
G. Zhang, J. Gu, C. Ding, X. Zheng, F. Cao, ACS Sustainable Chem.
Eng. 2017, 5, 6548; b) T. Rinesch, J. Mottweiler, M. Puche, P.
Concepción, A. Corma, C. Bolm, ACS Sustainable Chem. Eng. 2017, 5,
9818; c) M. Wang, J. Lu, X. Zhang, L. Li, H. Li, N. Luo, F. Wang, ACS
Catalysis 2016, 6, 6086.
[18] In general no ArCOF remained. For the less hindered substrates an
ArCO-based oligiomer forms, which also forms in the presence of just
K3PO4 and TESCF3 (see SI); this suggests that ArCOF decomposition
contributes to the yield of ArCF3.
[19] R. Grainger, J. Cornella, D. C. Blakemore, I. Larrosa, J. M. Campanera,
Chem. Eur. J. 2014, 20, 16680.
[20] a) P. T. Kaplan, J. A. Lloyd, M. T. Chin, D. A. Vicic, Beilstein J. Org.
Chem. 2017, 13, 2297; b) A. I. Konovalov, A. Lishchynskyi, V. V.
Grushin, J. Am. Chem. Soc. 2014, 136, 13410.
[21] Considering the high reaction temperatures, we investigated for the
possibility of Pd nanoparticles being involved. We observed no
induction period (ArCF3 formation in < 5 minutes, see SI). Pd
nanoparticles are therefore not likely catalyzing this transformation.
[22] M. J. Frisch et al., Gaussian 09, Revision D.01, Gaussian, Inc.,
Wallingford, CT, 2013 (see SI for full reference).
[23] For appropriateness of the chosen method see: T. Sperger, I. A.
Sanhueza, I. Kalvet, F. Schoenebeck, Chem. Rev. 2015, 115, 9532.
[24] For a recent review on distortion/interaction analyses see: F. M.
Bickelhaupt, K. N. Houk, Angew. Chem. Int. Ed. 2017, 56, 10070.
[25] While the decarbonylation of PhCO-[Pd(II)]-F resembles a 'mono-ligated'
transition state, the CO-loss from PhCO-[Pd(II)]-CF3 is 'bis-ligated'.
[26] ArCOCF3 4a forms through a Pd-catalysed process and cannot re-add to
the catalytic cycle (see SI).
[12] W. I. Dzik, P. P. Lange, Goo, Chem. Sci. 2012, 3, 2671.
4
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10.1002/anie.201800644
Angewandte Chemie International Edition
Layout 2:
Trifluoromethylation
S. T. Keaveney, F. Schoenebeck*
__________ Page – Page
Palladium-Catalyzed Decarbonylative
Trifluoromethylation of Acid Fluorides
5
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