Copper-Catalyzed Defluorinative Hydroarylation of Alkenes with Polyfluoroarenes

Article abstract of DOI:10.1002/anie.202010492

A catalytic defluorinative hydroarylation of alkenes with polyfluoroarenes in the presence of dppbz-ligated Cu catalyst and silanes was developed. This method provides a straightforward and alternative avenue to synthetic important polyfluorinated arenes with readily available and bench-stable alkenes as latent nucleophiles, and therefore avoids conventional reliance on stoichiometric quantities of organometallic reagents. This reaction proceeds under very mild conditions and exhibits good functional group compatibility and high level of regioselectivity. The synthetic potential of this method was further demonstrated by a gram-scale synthesis, and an array of experimental studies were also carried out to elaborate the probable mechanism.

Full text of DOI:10.1002/anie.202010492

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Accepted Article
Title: Copper-Catalyzed Defluorinative Hydroarylation of Alkenes with
Polyfluoroarenes
Authors: Xiaohong Li, Bin Fu, Qiao Zhang, Xiuping Yuan, Qian Zhang,
Tao Xiong, and Qian Zhang
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Copper-Catalyzed Defluorinative Hydroarylation of Alkenes with
Polyfluoroarenes
†
†
Xiaohong Li,[a] Bin Fu,[a] Qiao Zhang,[a] Xiuping Yuan,[a] Qian Zhang,[a] Tao Xiong,*[a] and Qian
Zhang[a][b]
[a]
X. Li, B. Fu, Q. Zhang, Prof. T. Xiong, Prof. Q. Zhang
Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry
Northeast Normal University
Changchun 130024, China
E-mail:xiongt626@nenu.edu.cn
[b]
Prof. Q. Zhang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
345 Lingling Lu, Shanghai 200032, China
[†] These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of the document.
Abstract: A catalytic defluorinative hydroarylation of alkenes with
polyfluoroarenes in the presence of dppbz-ligated Cu catalyst and
silanes was presented for the first time. This method provides a
straightforward and alternative avenue to synthetic important
polyfluorinated arenes with readily available and bench-stable
alkenes as latent nucleophiles, and therefore avoids conventional
reliance on stoichiometric quantities of organometallics. This
reaction proceeds under very mild conditions and exhibits good
functional group compatibility and high level of regioselectivity. The
synthetic potential of this method was further demonstrated by the
gram-scale synthesis, and an array of experimental studies were
also carried out to elaborate the probable mechanism.
The development of methods to synthesize polyfluorinated
arenes have evoked remarkable interest in the past decades
due to their prominent applications in materials science,
Scheme 1. The alkylation of polyfluoroarenes and CuH-catalyzed
agrochemicals, and pharmaceuticals (Figure 1),[1] such as the
top selling drugs Diflunisal I, Januvia II, the insect growth
regulator and chitinase inhibitor (Teflubenzuron III) and liquid
crystal material (IV). Among the various fluorination approaches,
catalytic fluorination of prefunctionalized arenes and directed C–
H fluorination have emerged as two most significant strategies to
provide fluorinated arenes in the past decades,[2] however, these
methods are not well suited for the synthesis of these
polyfluorinated arenes, since the starting materials would require
to preinstall multiple functional groups or uniquely arranged
directing groups. Actually, the dominant strategy up to now to
access such polyfluorinated arenes relies on the selective C–F
bond functionalization of easily accessible polyfluorinated
hydroarylation of alkenes and alkynes
arenes. Wheares the progress in this content is very sluggish,[3]
owing to the intrinsic inertness of the C–F bond, lacking an
efficient approach to realize the high site selectivity of
polyfluoroarenes, and the resulting problematic catalyst–F bonds
that often hamper catalyst turnover acting as a thermodynamic
sink in the catalytic cycle. In spite of these challenges, some
efficient catalytic methods have been successfully exploited. For
instance, impressive progress on hydrodefluorination (HDF) has
been successfully made in the past decades.[4] Some C–F bond
borylation reactions have also been developed with Rh, Ni, Cu,
and Co catalysis in recent years.[5] More recently, some
encouraging progresses in the areas of construction of C–CAr
bond via selective C–F bonds cleavage of simple
polyfluoroarenes with arylmetals (Ar–M, M = Mg, Zn, Si, and B)
have also been achieved by means of Ni and Pd catalysis.[6,7]
However,
transition-metal-catalyzed
alkylation
of
polyfluoroarenes remains a challenging objective in the realm of
C–F bond functionalization because of often accompanied with
undesirable β-H elimination, and only few examples with alkyl
organometallics as coupling partners have been disclosed so far
(Scheme 1A).[8] Whereas the requirement of prior preparation of
stoichiometric quantities of Grignard, organozinc and
Figure 1. Some important fluorinated pharamaceuticals, agrochemicals and a
liquid crystal
1
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10.1002/anie.202010492
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organolithium reagents along with the generation of metal salts
waste in these processes inevitably significantly limits the
functional group tolerance and synthetic efficiency. Besides,
either directing groups were required to preinstall to facilitate
ortho-selective C−F bond cleavage[8c-i] or 1,3-butadiene and
pentadiene as only valid alkylating reagents[8k-m] in these cases
that could further significantly restrict their widespread synthetic
applications. Therefore, the development of a new catalytic,
non-directing method, which has the capacity to circumvent
these limitations, would be particularly appealing.
Recently, the utilization of simple and stable unsaturated
hydrocarbons as the latent carbon nucleophiles in lieu of
preformed organometallics to couple with various electrophiles
by CuH catalysis has emerged as an attractive approach in
organic synthesis.[9] In this content, some important progress on
hydroarylation[10] of olefins and alkynes has also been achieved
more recently through a synergistic CuH/Pd catalysis. For
instance, Semba, Sakaki, and Nakao pioneered a hydroarylation
of styrenes with aryl bromides in 2016.[11] Almost simultaneously,
Buchwald and co-workers elegantly realized the asymmetric
version by combination of a Pd catalyst and a chiral CuH
catalyst.[12] Subsequently, Buchwald, Lalic, and Hull
independently reported the hydroarylation of terminal olefins and
alkynes with aryl bromides or aryl iodides.[13,14] Despite these
advances, aryl halides (ArBr, and ArI) were the only valid aryl
electrophiles and precious Pd catalyst was necessary to
To our knowledge, the more challenging hydroarylation of
unsaturated hydrocarbons with polyfluoroarenes via base-metal-
catalyzed C–F bond cleavage remains elusive so far. Actually,
only one example for the hydrodefluorination of fluoroarenes has
been disclosed to date by Zhang and co-workers in the context
of CuH chemistry.[4k] As our continuing interest in Cu-catalyzed
hydrofunctionalization of unsaturated hydrocarbons,[15] we herein
describe the first Cu-catalyzed hydroarylation of alkenes with
ployfluoroarenes in a regioselective C–F bond cleavage fashion,
without requirement of preformed organometallics and precious
Pd catalyst in previous reports (Scheme 1C).
We began to investigate the defluorinative hydroarylation with
the readily available alkene 1a and polyfluoroarene 2a as the
model substrates. After extensive screening of reaction
conditions, we were pleased to find that the Xantphos-ligated
Cu(C8H15O2)2 was effective in this defluorinative hydroarylation,
despite relatively low yield (Table 1, entry 1). Further screening
of various ligands found that dppbz-ligated Cu(C8H15O2)2
showed most efficiency for this reaction, providing 3a in nearly
quantitative yield (Table 1, entries 2-5). Subsequently, different
Cu salts and solvents were also evaluated, resulting in either
lower yields or completely ineffective with dppbz-ligated CuCl as
Table 2. The scope of defluorinative hydroarylation[a]
efficiently perform the transformations (Scheme 1B).[11-13,14a,b]
Table 1. Optimized reaction conditions for defluorinative hydroarylation of
alkene[a]
Entry
Catalyst
Ligand
Solvent
Yield (%)[b]
1
Cu(C8H15O2)2
Cu(C8H15O2)2
Cu(C8H15O2)2
Cu(C8H15O2)2
Cu(C8H15O2)2
Cu(OAc)2
Xantphos
BINAP
dppf
THF
30
2
THF
N.R.
N.D.
90
3
THF
4
dppe
THF
5
dppbz
dppbz
dppbz
dppbz
dppbz
dppbz
dppbz
THF
97
6
THF
90
7
CuCl
THF
N.D.[c]
90
8
Cu(C8H15O2)2
Cu(C8H15O2)2
Cu(C8H15O2)2
Cu(C8H15O2)2
Et2O
dioxane
CyH
9
95
10
11
27
toluene
48
[a] Reaction conditions: 1 (0.30 mmol, 1.5 equiv), 2 (0.20 mmol), Cu(C8H15O2)2
(5 mol%), dppbz (6 mol%), DMMS (0.30 mmol, 1.5 equiv), THF (2 mL), 30 oC,
N2, 30 h; isolated yields. [b] Cu(C8H15O2)2 (10 mol%), dppbz (12 mol%), 40 oC.
[c] Cu(C8H15O2)2 (10 mol%), dppbz (12 mol%), 50 oC, 48 h. [d] 1 (0.20 mmol),2
(0.60 mmol, 3.0equiv), DMMS (0.60 mmol, 3.0 equiv). [e] chemoselectivity:
80 :7. [f] Cu(C8H15O2)2 (10 mol%), dppbz (12 mol%), 1 (0.60 mmol, 3.0equiv),
2 (0.20 mmol), DMMS (0.60 mmol, 3.0 equiv), 40 oC. [g] Site selectivities were
determined by 1H NMR and 19F NMR. [h] Cu(C8H15O2)2 (10 mol%), dppbz (12
mol%), 40 oC, 48 h.
[a] Reaction conditions: 1a (0.30 mmol, 1.5 equiv), 2a (0.20 mmol), catalyst
(0.01 mmol, 5 mol%), ligand (0.012 mmol, 6 mol%), DMMS (0.30 mmol, 1.5
equiv) in 2 mL dry solvent at 30 oC for 30 h; Cu(C8H15O2)2: copper bis(2-
ethylhexanoate); DMMS: Me(MeO)2SiH; N. D.: not detected; N. R. no reaction.
[b] Yields were estimated by 1H NMR spectroscopy of the crude mixture with
CH2Br2 as an internal standard. [c] NaOtBu (0.04 mmol) was used.
2
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the catalyst in the presence of NaOtBu as the base (Table 1,
entries 6-11).
Having established the optimal catalytic system, we next
subjected a range of sterically and electronically diverse alkenes
to this Cu-catalyzed defluorinative hydroarylation. As illustrated
in Table 2, ortho-, meta-, and para-phenyl substituted styrenes
can be converted into the expected products 3a-3c in good to
excellent yields, and relatively low yield was observed for 3c,
probably owing to the crowed steric hindrance. Styrene and its
derivatives which bears various electronic-donating functional
groups including -OMe, -Me and -SMe on the aromatic rings
were also effectively coupled with 2a, providing corresponding
products 3d-3h in 58-98% yields. In addition, an array of
styrenes bearing various electronic-withdrawing substituents,
such as -F, -Cl, -Br, -CF3, and -C(O)C6H5 were also smoothly
transferred into corresponding products 3i-3o with high
efficiency. It’s notable that the keto group in styrene 1l, which is
readily reduced into hydroxyl group under CuH catalysis,[9,16] was
accommodated and corresponding reduction product was not
observed, implying good chemoselectivity of this catalytic
system. 1,4-Divinylbenzene 1o can be selectively mono- or
dihydroarylated by tuning the ratio of alkene 1o to
polyfluoroarene 2a, furnishing corresponding products 3o and
3p in 90% and 75% yields, respectively. Polycyclic aryl alkenes
1q-1s and heteroaryl substituted alkene 1t showed excellent
reactivities, offering hydroarylation products 3q-3t in over 90%
yields. Moreover, the hydroarylation could be chemoselectively
occurred at the terminal alkenyl group in the presence of either
internal alkenyl or internal alkynyl group, as demonstrated by 3u
and 3v. In spite of this, to our delight, internal alkene 1w could
be amenable to this defluorinative hydroarylation. Additionally,
activated alkene 1x and 1y can also undergo this transformation,
providing corresponding desired product 3x and 3y, and the
regioselectivity was further determined by deuterium experiment
(see supporting information for details). After examination the
scope of alkene, we next turned our attention to assess the
scope of polyfluoroarenes 2. A series of polyfluoroarenes
bearing various functionalities, including alkyl, alkoxyl,
(hetero)aryl, amide, ester, fluorine, and trifluoromethyl moieties
were competent coupling partners, providing hydroarylation
products 3z-3ak in generally excellent yields. Moreover, two C–
F bonds can be effectively activated with hexafluorobenzene as
reactant, and corresponding double alkylation product 3al can
be obtained in 95% yield. Other polyfluoroarenes were also
assessed, and can be transferred into corresponding
products3am and 3an in 85% and 55% yields, respectively,
along with observing low site selectivity for 3am. Complex-
molecules-derived substrates, such as L-menthol- and
cholesterol-derived polyfluoroarenes, were also valid substrates,
and can be converted into defluorinative products 3ao and 3ap
in moderated yields. It is noteworthy that almost all of these
transformations exhibited excellent level of site selectivities,
which might be ascribed to the joint effects of the steric
hindrance of substituents in polyfluoroarenes and in-situ
generated alkylcopper nucleophiles.[8k-m,17]
Scheme 2. Gram-scale synthesis and mechanism studies
mechanistic insight into this defluorinative hydroarylation
reaction, some control experiments were conducted (Scheme
2B). We firstly performed the reaction under optimal reaction
t
conditions with BuOH as an additive to probe the possible
intermediate, and 3a was only obtained in 5% yield, along with
the reductive product 4 of alkene 1a in 17% yield and 2a in 90%
yield. This indicated that the insertion of in-situ generated CuH
catalyst into alkene should take precedence of the
hydrodefluorination of 2a, and then the resulting alkylcuprate
t
intermediate was trapped by BuOH providing reductive product
4. Moreover, for the possibility of a single-electron-transfer (SET)
process,[17] the standard reaction can be carried out with almost
negligible effect by adding some extensively π-conjugated
arenes
or
electron-deficient
arene,
such
as
(trifluoromethyl)benzene, naphthalene and 1,1-diphenylethylene.
These observations suggested the SET might be not involved in
this catalytic cycle. We also conducted competitive reactions of
pentafluorotoluene
with
substituted
pentafluorobenzene
(Scheme 2C). When a 1 : 1 :1 mixture of 1a, pentafluorotoluene,
and phenyl substituted pentafluorobenzene reacted under the
optimized conditions, 3z and 3ab were obtined in 4% and 80%
yield, respectively. In addition, a similar competitive experiment
with N,N-diethylpentafluorobenzamide instead of phenyl
substituted pentafluorobenzene was also carried out, resulting in
formation of 3a in 82% yield while only trace of 3z was observed.
These results indicated the electron-deficient polyfluoroarene
A gram-scale synthesis was performed to demonstrate the
practicability of this method. As illustrated Scheme 2A, the
expected product 3a can be isolated in 88% yield (1.89 g) with 2
mol% copper catalyst and 2.5 mol% dppbz. To gain further
3
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1881–1886; d) A. R. Murphy, J. M. J. Fréchet, Chem. Rev. 2007, 107,
1066–1096; e) F. Badudri, G. M. Farinola, F. Naso, R. Ragni, Chem.
Commun. 2007, 1003–1022; f) S. Preshlock, M. Tredwell, V.
Gouverneur, Chem. Rev. 2016, 116, 719–766.
displayed higher reactivity than electron-rich one, and therefore
provides positive evidance that this defluorinative hydroarylation
might undergo a SNAr mechanism.[8k-m] The relationship of
relative stoichiometry of ligand and copper catalyst was also
investigated. As shown in Scheme 2D, the initial reaction rate
increased with the increasing of [L], and initial reaction rate
culminated when [L]/[Cu] ≈ 1. On the basis of this result, we
deduced that active catalyst incorporates only one ligand. Based
[2]
For selected reviews, see: a) T. Liang, C. N. Neumann, T. Ritter, Angew.
Chem. Int. Ed. 2013, 52, 8214–8264; Angew. Chem. 2013, 125, 8372–
8423; b) A. Lin, C. B. Huehls, J. Yang, Org. Chem. Front. 2014, 1, 434–
438; c) Y. Li, G-S. Li, X.-S. Wang, Adv. Synth. Catal. 2014, 356, 871; d)
R. Szpera, D. F. J. Moseley, L. B. Smith, A. J. Sterling, V. Gouverneur,
Angew. Chem. Int. Ed. 2019, 58, 14824–14848; Angew. Chem. 2019,
131, 14966–14991.
on these experimental results and previous reports,[8k-m]
a
possible mechanism was described in Scheme 3. Initially, the
combination of Cu(C8H15O2)2, dppbz, and silane would in-situ
generate dppbz-ligated CuH catalyst. Then, a regioselective
insertion of CuH catalyst into alkene could provide
[3]
[4]
a) J. L. Kiplinger, T. G. Richmond, C. E. Osterberg, Chem. Rev. 1994,
94, 373–431; b) T. Braun, R. N. Perutz, Chem. Commun. 2002, 23,
2749–2757; c) W. D. Jones, Dalton Trans. 2003, 3991–3995; d) H. Amii,
K. Uneyama, Chem. Rev. 2009, 109, 2119–2183; e) T. Ahrens, J.
Kohlmann, M. Ahrens, T. Braun, Chem. Rev. 2015, 115, 931–972; f) O.
Eisenstein, J. Milani, R. N. Perutz, Chem. Rev. 2017, 117, 8710–8753.
For reviews, see: a) G. Meier, T. Braun, Angew. Chem. Int. Ed. 2009, 48,
1546–1548; Angew. Chem. 2009, 121, 1575–1577; b) E. Clot, O.
Eisenstein, N. Jasim, S. A. Macgregor, J. E. McGrady, R. N. Perutz,
Acc. Chem. Res. 2011, 44, 333–348; c) M. F. Kuehnel, D. Lentz, T.
Braun, Angew. Chem. Int. Ed. 2013, 52, 3328–3348; Angew. Chem.
2013, 125, 3412–3433; For selected examples, see: d) M. Aizenberg, D.
Milstein, Science. 1994, 265, 359–361; e) M. Aizenberg, D. Milstein, J.
Am. Chem. Soc. 1995, 117, 8674–8675; f) T. Schaub, P. Fischer, A.
Steffen, T. Braun, U. Radius, A. Mix, J. Am. Chem. Soc. 2008, 130,
9304–9317; g) N. Y. Adonin, V. F. Starichenko, J. Fluorine. Chem. 2000,
101, 65–67; h) H. Lv, J.-H. Zhan, Y.-B. Cai, Y. Yu, B. Wang, J.-L.
Zhang, J. Am. Chem. Soc. 2012, 134, 16216–16227; i) P. Fischer, K.
Götz, A. Eichhorn, U. Radius, Organometallics. 2012, 31, 1374–1383; j)
J.-H. Zhan, H. B. Lv, Y. Yu, J.-L. Zhang, Adv. Synth. Catal. 2012, 354,
1529–1541; k) H. B. Lv, Y.-B. Cai, J.-L. Zhang, Angew. Chem. Int. Ed.
2013, 52, 3203–3207; Angew. Chem. 2013, 125, 3285–3289; l) S. M.
Senaweera, A. Singh, J. D. Weaver, J. Am. Chem. Soc. 2014, 136,
3002–3005; m) J. Lu, N. S. Khetrapal, J. A. Johnson, X. C. Zeng, J.
Zhang, J. Am. Chem. Soc. 2016, 138, 15805–15808; n) M. K. Cybulski,
J. E. Nicholls, J. P. Lowe, M. F. Mahon, M. K. Whittlesey,
Organometallics. 2017, 36, 2308–2316.
organocuprate intermediate I, followed by
a nucleophilic
substitution to polyfluoroarene 2 that could directly furnish target
product 3 and simultaneously release dppbz-ligated CuF.[8k-m]
Finally, a metathesis reaction between LCuF and silane could
regenerate CuH catalyst.
Scheme 3. Proposed mechanism for the defluorinative hydroarylation of
alkenes
[5] a) T. Braun, M. Ahijado Salomon, K. Altenhöner, M. Teltewskoi, S.
Hinze,Angew. Chem. Int. Ed. 2009, 48, 1818–1822; Angew. Chem.
2009, 121, 1850–1854; b) M. Teltewskoi, J. A. Panetier, S. A.
Macgregor, T. Braun, Angew. Chem. Int. Ed. 2010, 49, 3947–3951;
Angew. Chem. 2010, 122, 4039–4043; c) W. H. Guo, Q. Q. Min, J. W.
Gu, X. Zhang, Angew. Chem. Int. Ed. 2015, 54, 9075–9078; Angew.
Chem. 2015, 127, 9203–9206; d) R. J. Lindup, T. B. Marder, R. N.
Perutz, A. C. Whitwood, Chem. Commun. 2007, 3664–3666; e) X. W.
Liu, J. Echavarren, C. Zarate, R. Martin, J. Am. Chem. Soc. 2015, 137,
12470–12473; f) T. Niwa, H. Ochiai, Y. Watanabe, T. Hosoya, J. Am.
Chem. Soc. 2015, 137, 14313–14318; g) S. I. Kalläne, M. Teltwskoi, T.
Braun, B. Braun, Organometallics. 2015, 34, 1156–1169; h) J. Zhou, M.
W. Kuntze-Fechner, R. Bertermann, U. S. D. Paul, J. H. J. Berthel, A.
Friedrich, Z. Du, T. B. Marder, U. Radius, J. Am. Chem. Soc. 2016, 138,
5250–5253; i) Y.-M. Tian, X.-N. Guo, M. W. Kuntze-Fechner, I.
Krummenacher, H. Braunschweig, U. Radius, A. Steffen, T. B. Marder,
J. Am. Chem. Soc. 2018, 140, 17612–17623.
In summary, we have developed a novel copper-catalyzed
defluorinative hydroarylation of alkenes with polyfluoroarenes,
providing an array of synthetic important fluorinated arenes with
high efficiency. This method not only exhibits good substrate
scope, functional group compatibility and generally excellent
level of regioselectivity, but also offers a straightforward, mild,
and alternative approach in the field of C–F bond
functionalization via readily available alkenes as the latent
preformed organometallics surrogates. Further detailed
mechanistic studies and enantioselective version are in progress
in our laboratory.
Acknowledgements
[6]
Ni-catalyzed arylation, see: a) N. Yoshikai, H. Mashima, E. Nakamura, J.
Am. Chem. Soc. 2005, 127, 17978–17979; b) T. Saeki, Y. Takashima,
K. Tamao, Synlett. 2005, 11, 1771–1774; c) T. Schaub, M. Backes, U.
Radius, J. Am. Chem. Soc. 2006, 128, 15964–15965; d) A. D. Sun, J. A.
Love, Org. Lett. 2011, 13, 2750–2753; e) M. Tobisu, T. Xu, T.
Shimasaki, N. Chatani, J. Am. Chem. Soc. 2011, 133, 19505–19511; f)
Y. Nakamura, N. Yoshikai, L. Ilies, E. Nakamura, Org. Lett. 2012, 14,
3316–3319; g) M. Ohashi, H. Saijo, M. Shibata, S. Ogoshi, Eur. J. Org.
Chem. 2013, 2013, 443–447; h) H. Saijo, H. Sakaguchi, M. Ohashi, S.
Ogoshi, Organometallics. 2014, 33, 3669–3672; i) J. Zhou, J. H. J.
Berthel, M. W. Kuntze-Fechner, A. Friedrich, T. B. Marder, U. Radius,
J. Org. Chem. 2016, 81, 5789–5794; j) F. Zhu, Z.-X. Wang, J. Org.
Chem. 2014, 79, 4285–4292. Example on Ni-catalyzed C–H activation
We acknowledge the NSFC (21672033, 21801039 ， and
21831002), Jilin Educational Committee (JJKH20190269KJ), the
Fundamental Research Funds for the Central Universities, and
Ten Thousand Talents Program for generous financial support.
Keywords: defluorinative hydroarylation •copper catalysis •
alkenes • polyfluoroarenes
[1]
For selected reviews, see: a) T. Hiyama, Organofluorine Compounds,
Chemistry and Applications, Springer-Verlag: Berlin, 2000; b) S. Purser,
P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37,
320–330; c) K. Müller, C. Faeh, F. Diederich, Science. 2007, 317,
4
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for the synthesis of polyfluoroarenes, see: k) Y. Nakao, N. Kashihara, K.
2017, 129, 13310–13314; b) G. Xu, B. Fu, H. Zhao, Y. Li, G. Zhang, Y.
Wang, T. Xiong, Q. Zhang, Chem. Sci. 2019, 10, 1802–1806; c) B. Fu,
X. Yuan, Y. Li, Y. Wang, Q. Zhang, T. Xiong, Q. Zhang, Org. Lett. 2019,
21, 3576–3580; d) H. Wang, G. Zhang, Q. Zhang, Y. Wang, Y. Li, T.
Xiong, Q. Zhang, Chem. Commun. 2020, 56, 1819–1822; e) G. Zhang,
Y. Li, Y. Wang, Q. Zhang, T. Xiong, Q. Zhang, Angew. Chem. Int. Ed.
2020, 59, 11927–11931; Angew. Chem. 2020, 132, 12025–12029; f) G.
Zhang, Y. Liang, T. Qin, T. Xiong, S. Liu, W. Guan and Q. Zhang, CCS
Chem. 2020, doi: 10.31635/ccschem.020.202000434.
S. Kanyiva, T. Hiyama, J. Am. Chem. Soc. 2008, 130, 16170-16171.
[7]
Pd-catalyzed arylation, see: a) S. A. Macgregor, D. C. Roe, W. J.
Marshall, K. M. Bloch, V. I. Bakhmutov, V. V. Grushin, J. Am. Chem.
Soc. 2005, 127, 15304–15321; b) M. R. Cargill, G. Sandford, A. J.
Tadeusiak, D. S. Yufit, J. A. K. Howard, P. Kilickiran, G. Nelles, J. Org.
Chem. 2010, 75, 5860–5866; c) D. Yu, L. Lu, Q. Shen, Org. Lett. 2013,
15, 940–943; d) M. Ohashi, R. Doi, S. Ogoshi, Chem. Eur. J. 2014, 20,
2040–2048; e) Z.-J. Luo, H.-Y. Zhao, X. Zhang, Org. Lett. 2018, 20,
2543–2546; f) D. Breyer, T. Braun, P. Klꢀring, Organometallics. 2012,
31, 1417–1424.
[16] For selected examples, see: a) B. H. Lipshutz, K. Noson, W. Chrisman,
J. Am. Chem. Soc. 2001, 123, 12917–12918; b) B. H. Lipshutz, K.
Noson, W. Chrisman, A. Lower, J. Am. Chem. Soc. 2003, 125, 8779–
8789; c) S.-L. Shi, Z. L. Wong, S. L. Buchwald, Nature. 2016, 532, 353–
356.
[8]
a) Y. Kiso, K. Tamao, M. Kumada, J. Organomet. Chem. 1973, 50,
C12−C14; b) H. Guo, F. Kong, K.-I. Kanno, J. He, K. Nakajima, T.
Takahashi, Organometallics. 2006, 25, 2045–2048; c) T. Wang, B. J.
Alfonso, J. A. Love, Org. Lett. 2007, 9, 5629–5631; d) H. L. Buckley, A.
D. Sun, J. A. Love, Organometallics. 2009, 28, 6622–6624; e) A. D.
Sun, J. A. Love, J. Fluorine. Chem. 2010, 131, 1237–1240; f) X. Yang,
H. Sun, S. Zhang, X. Li, J. Organomet. Chem. 2013, 723, 36–42; g) A.
D. Sun, K. Leung, A. D. Restivo, N. A. LaBerge, H. Takasaki, J. A. Love,
Chem. Eur. J. 2014, 20, 3162–3168; h) S.-H. Xiao, Y. Xiong, X.-X.
Zhang, S. Cao, Tetrahedron. 2014, 70, 4405–4411; i) D. Yu, C.-S.
Wang, C. Yao, Q. Shen, L. Lu, Org. Lett. 2014, 16, 5544–5547; j) Y. A.
Ho, M. Leiendecker, X. Liu, C. Wang, N. Alandini, M. Rueping, Org. Lett.
2018, 20, 5644–5647; k) T. Iwasaki, A. Fukuoka, X. Min, W. Yokoyama,
H. Kuniyasu, N. Kambe, Org. Lett. 2016, 18, 4868–4871; l) T. Iwasaki,
K. Okamoto, H. Kuniyasu, N. Kambe, Chem. Lett. 2017, 46, 1504–
1507; m) T. Iwasaki, X. Min, A. Fukuoka, L. Zhu, R. Qiu, T. Yang, M.
Ehara, A. Sudalai, N. Kambe, J. Org. Chem. 2018, 83, 9267–9277.
[17] W. Lu, J. Gao, J.-K. Yang, L. Liu, Y. Zhao, H.-C. Wu. Chem. Sci. 2014,
5, 1934-1939.
[18] T. Niwa, H. Ochiai, T. Hosoya, ACS Catal. 2017, 7, 4535–4541.
[9] For reviews on CuH-catalyzed reactions, see: a) S. Rendler, M. Oestreich,
Angew. Chem. Int. Ed. 2007, 46, 498–504; Angew. Chem. 2007, 119,
504–510; b) C. Deutsch, N. Krause, B. H. Lipshutz, Chem. Rev. 2008,
108, 2916–2927; c) T. Fujihara, K. Semba, J. Terao, Y. Tsuji, Catal. Sci.
Technol. 2014, 4, 1699–1709; d) M. T. Pirnot, Y.-M. Wang, S. L.
Buchwald, Angew. Chem. Int. Ed. 2016, 55, 48–57; Angew. Chem.
2016, 128, 48–57; e) A. J. Jordan, G. Lalic, J. P. Sadighi, Chem. Rev.
2016, 116, 8318–8372; f) J. Chen, J. Guo, Z. Lu, Chin. J. Chem. 2018,
36, 1075–1109.
[10] For reviews on direct Brønsted or Lewis acid-catalysed Friedel-Crafts
type hydroarylation reaction, see: a) G. A. Olah, R. Krishnamurti, G. K.
S. Prakash in Friedel–Crafts Alkylation in Comprehensive Organic
Synthesis, Vol. 3 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford,
1991, pp. 293; b) M. Rueping, B. J. Nachtsheim, Beilstein J. Org. Chem.
2010, 6, 6; c) Catalytic Hydroarylation of Carbon–Carbon Multiple
Bonds (Eds.: L. Ackermann, B. T. Gunnoe, L. Goj Habgood), Wiley-
VCH, Weinheim, 2018; for reviews on transition-metal-catalyzed
hydroarylation reaction, see: d) V. Ritleng, C. Sirlin, M. Pfeffer, Chem.
Rev. 2002, 102, 1731-1769; e) D. A. Colby, R. G. Bergman, J. A.
Ellman, Chem. Rev. 2010, 110, 624–655; f) Z. Dong, Z. Ren, S. J.
Thompson, Y. Xu, G. Dong, Chem. Rev. 2017, 117, 9333-9403; for
examples on alkaline-earth-catalyzed hydroarylation, see: g) C. Qi, V.
Gandon, D. Leboeuf, Angew. Chem. Int. Ed. 2018, 57, 14245–14249;
Angew. Chem. 2018, 130, 14441-14445; h) A. S. S. Wilson, M. S. Hill,
M. F. Mahon, C. Dinoi, L. Maron, Science 2017, 358, 1168-1171; i) B.
Rösch, T. X. Gentner, H. Elsen, C. A. Fischer, J. Langer, M. Wiesinger,
S. Harder, Angew.Chem. Int. Ed. 2019, 58, 5396 –5401; Angew. Chem.
2019, 131, 5450-5455.
[11] K. Semba, K. Ariyama, H. Zheng, R. Kameyama, S. Sakaki, Y. Nakao,
Angew. Chem. Int. Ed. 2016, 55, 6275–6279; Angew. Chem. 2016, 128,
6383–6387.
[12] S. D. Friis, M. T. Pirnot, S. L. Buchwald, J. Am. Chem. Soc. 2016, 138,
8372–8375.
[13] S. D. Friis, M. T. Pirnot, L. N. Dupuis, S. L. Buchwald, Angew. Chem. Int.
Ed. 2017, 56, 7242–7246; Angew. Chem. 2017, 129, 7348–7352.
[14] a) M. K. Armstrong, M. B. Goodstein, G. Lalic, J. Am. Chem. Soc. 2018,
140, 10233–10241. b) M. K. Armstrong, G. Lalic, J. Am. Chem. Soc.
2019, 141, 6173–6179. c) G. D. Kortman, K. L. Hull, ACS Catal. 2017,
7, 6220−6224
[15] a) G. Xu, H. Zhao, B. Fu, A. Cang, G. Zhang, Q. Zhang, T. Xiong, Q.
Zhang, Angew. Chem. Int. Ed. 2017, 56, 13130–13134; Angew. Chem.
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10.1002/anie.202010492
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An efficient and straightforward defluoriantive hydroarylation of alkenes with polyfluoroarenes was achieved for the first time with in-
situ generated CuH catalysis. Consequently, an array of fluorinated arenes through regioselective C–F bond activation manner was
obtained in generally good yields under very mild conditions. Furthermore, this method also displayed good substrate scope,
functional group compatibility due to with readily available and bench-stable alkenes as the latent nucleophiles and therefore averting
conventional preformed organometallics.
6
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