Pd/Cu-Catalyzed Defluorinative Carbonylative Coupling of Aryl Iodides and gem-Difluoroalkenes: Efficient Synthesis of α-Fluorochalcones

Article abstract of DOI:10.1002/anie.202017365

An unprecedented and challenging defluorinative carbonylation was achieved. Enabled by a Pd/Cu cooperative catalyst system, the first example of defluorinative carbonylative coupling has been established. With gem-difluoroalkenes and aryl iodides as the substrates, this methodology offers flexible and facile access to privileged α-fluorochalcones under mild reaction conditions in moderate-to-excellent yields. Mechanistic studies indicated transmetalation between palladium and copper intermediates as a crucial step of the catalytic cycle.

Full text of DOI:10.1002/anie.202017365

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How to cite: Angew. Chem. Int. Ed. 2021, 60, 8818–8822
International Edition:
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doi.org/10.1002/anie.202017365
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Synthetic Methods
Hot Paper
Pd/Cu-Catalyzed Defluorinative Carbonylative Coupling of Aryl
Iodides and gem-Difluoroalkenes: Efficient Synthesis of
a-Fluorochalcones
Fu-Peng Wu, Yang Yuan, Jiawang Liu, and Xiao-Feng Wu*
Dedicated to Professor Ilhyong Ryu on the occasion of his 70th birthday
À
Abstract: An unprecedented and challenging defluorinative
carbonylation was achieved. Enabled by a Pd/Cu cooperative
catalyst system, the first example of defluorinative carbon-
ylative coupling has been established. With gem-difluoroal-
kenes and aryl iodides as the substrates, this methodology
offers flexible and facile access to privileged a-fluorochalcones
under mild reaction conditions in moderate-to-excellent yields.
Mechanistic studies indicated transmetalation between palla-
dium and copper intermediates as a crucial step of the catalytic
cycle.
steps in these transformations is the activation of the C F
bond by b-F elimination or oxidative insertion under the
assistant of directing group.[7o,p,q] To the best of our knowl-
À
edge, despite these successful examples, carbonylation of C F
bond has not been realized yet. Therefore, developing a new
method of defluorinative carbonylation is still desirable.
According to our research experience on carbonylation,[10]
À
under the atmosphere of CO, the oxidative addition of C F
bond with metal center[11] usually is challenge due to the
inhibitory influence of CO coordination to the metals and also
[12]
À
the strong C F bond energy
(120–129 kcalmolÀ1 for
À
T
he incorporation of a fluorine or fluorine-containing frag-
olefinic C F bonds). More recently, Toste and their co-
workers reported a palladium-catalyzed defluorinative cou-
pling of difluoroalkenes and boronic acids.[7f] This reaction
was postulated to proceed via the insertion of aryl-Pd
complex into a gem-difluoroalkene to produce alkyl-Pd
intermediate, which could deliver the final alkene product
after b-F elimination [Scheme 1, Eq. (b)]. Similarly, carbon-
ylative Heck reaction was developed and also undergo the
insertion of acyl-Pd intermediate into olefin and followed
by b-H elimination to give the final product [Scheme 1,
Eq. (c)].[13] However, a large excess of olefins (at least
6 equiv) is typically required. Based on the above mechanistic
ment into organic molecules can generally have a positive
influence on physical and biological properties, such as
increasing the solubility, lipophilicity, and metabolic stability
of the parent molecules.[1] In particular, monofluoroalkenes
have attracted considerable interests from chemical com-
munity as monofluoroalkenes exhibit a similar electronic and
steric properties as amide bonds, which means fluoroalkenes
are excellent mimics of peptide bonds. Monofluoroalkenes
mimic of bioactive amides have been widely used to enhance
biological properties.[2] However, the synthesis of monofluor-
oalkenes is not a trivial task.[3] In recent years, gem-
difluoroalkene moiety has been used as an ideal precursor
for the preparation of monofluoroalkenes via defluorinative
functionalization.[4] For example, Fu and co-workers realized
a nickel-catalyzed defluorinative reductive cross-coupling of
alkyl halides with gem-difluoroalkenes in 2017.[5] Addition-
ally, several other original transformation on defluorinative
functionalization of gem-difluoroalkenes were established
À
considerations, we speculate that carbonylation of C F bond
independently, including defluorinative nucleophilic addi-
[7]
tion,[6] cross-coupling via C H/C F activation, reductive
coupling of electrophile[8] and Cu-catalyzed defluorinative
carboxylative reaction[9] [Scheme 1, Eq. (a)]. One of the key
À
À
[*] F.-P. Wu, Y. Yuan, Dr. J. Liu, Prof. Dr. X.-F. Wu
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Straße 29a, 18059 Rostock (Germany)
E-mail: xiao-feng.wu@catalysis.de
Prof. Dr. X.-F. Wu
Dalian National Laboratory for Clean Energy
Dalian Institute of Chemical Physics
Chinese Academy of Sciences
116023, Dalian, Liaoning (China)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202017365.
Scheme 1. Defluorinative functionalization.
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Table 1: Optimization of reaction conditions.[a]
Scheme 2. Selected examples of bioactive a-fluorinated enone deriva-
tives.
can potentially be achieved via b-F elimination with gem-
difluoroalkenes as the substrates [Scheme 1, Eq. (d)].
Entry
Variations from standard conditions
Yield [%][b]
On the other hand, as the products, a-fluorinated enones
represent an important molecular skeleton with potent
biomedical applications (Scheme 2).[14] Herein, we report
a Pd/Cu catalyzed defluorinative carbonylative coupling of
aryl iodides and gem-difluoroalkenes to access single isomer
of a-fluorochalcones under mild reaction conditions. It is
noteworthy that despite great achievements in the carbon-
ylative coupling reactions, this work represents the first
example on defluorinative carbonylation.
1
2
3
4
5
6
7
8
none
74(0)
0(31)
0(25)
27(15)
4(38)
8(16)
3(35)
56(21)
70(0)
70(0)
66(0)
62(0)
19(15)
12(20)
63(6)
w/o CuCl or PdCl2 or DPPP
Mn or Zn instead of B2pin2/LiOMe
L1 instead of L2
L3 instead of L2
L4 instead of L2
L5 instead of L2
DPPP (10 mol%) instead of DPPP (4 mol%)
Pd(OAc)2 instead of PdCl2
[Pd(h3-C3H5)Cl]2 instead of PdCl2
CuTc instead of CuCl
9
10
11
13
14
15
16
We commenced our studies with 4-(2,2-difluorovinyl)-
1,1’-biphenyl (1a) and iodobenzene (2a) as the model
substrates and the influence of all reaction parameters were
systematically evaluated (see Supporting information for
details). After intensive investigations, we found that the
desired a-fluorochalcone 3a can be obtained in 74% yield
when CuCl/PdCl2 as the catalyst, DPPP as the ligand and
LiOMe as the base in presence of B2pin2 at 608C under 10 bar
CO atmosphere was applied (Table 1, entry 1). The Z-
fluorinated vinylboronate ester 3a’ was the main by-product
during the process of our studies. In our control experiments,
copper, palladium, and ligand were proven all essential for the
success of this transformation (Table 1, entry 2). The role of
B2pin2 and base in the reaction can not be replaced by the
other reductants such as Zn or Mn (Table 1, entry 3).[7k,n] In
the testing of various phosphine ligands, DPPP was found to
be superior to the other tested ligands (Table 1, entries 4–7).
Increasing the load of the dppp inhibited the reaction,
indicating that the ligand only coordinates with palladium
metal. With increased loading of phosphine ligand can
improve the reaction outcome significantly, due to that
excess phosphine ligand (Pd/P = 1:4) may be used to reduce
PdII to Pd0 and stabilize the active palladium species.
Furthermore, different Pd and Cu precursors were studied
as well. Palladium precursors have little influence on the
reaction result while a slightly decreased yield was observed
the other tested copper salts (Table 1, entries 9–13). The
loading of B2pin2 is critical to the reaction, and only
stoichiometric amount of B2pin2 can promote the catalytic
cycle (Table 1, entries 14 and 15). Excess amount of B2pin2
can significantly reduce the yield of product 3a, because 3a
will further react with excess B2pin2 to give a complexed
reaction mixture (see supporting information). To our delight,
63% yield of 3a can still be obtained under 5 bar of CO
(Table 1, entry 16). Notably, this formal defluorinative car-
bonylation proceeded with high efficiency and high selectiv-
ity, only (Z)-isomer product can be detected here and
confirmed by 19F NMR.
CuOAc instead of CuCl
0.5 equiv B2pin2 instead of 1.0 equiv B2Pin2
1.5 equiv B2pin2 instead of 1.0 equiv B2Pin2
CO (5 bar) instead of CO (10 bar)
[a] Reaction conditions: 1a (0.2 mmol), 2a (1.2 equiv), CuCl (10 mol%),
PdCl2 (2 mol%), DPPP (4 mol%), B2pin2 (1.0 equiv), LiOMe (3.0 equiv),
CO (10 bar), DMAc (0.2 M), 608C, 20 h, yields were determined by GC
using hexadecane as the internal standard. [b] Yield of 3a’ shown in
parentheses. DMAc: N,N-dimethylformamide.
With the optimized reaction conditions in hand, we
examined the scope of gem-difluoroalkenes and aryl iodides
for this transformation. As shown in the Table 2, gem-
difluoroalkenes spanning a range of electronic properties
were tested for this process. gem-Difluoroalkenes bearing
electron-donating groups such as tert-butyl, ether and sulfide
afforded the corresponding a-fluorochalcones in moderate
yields (3b–3 f). In contrast, chloro, bromo, cyano, ester,
thiophene and furan were compatible better with the reaction
conditions to produce the target products in moderate to
excellent yields (3g–3o). Importantly, the more challenging
gem-difluorodienes were also suitable starting materials here,
afforded the desired products with good regio- and stereose-
lectivity, thus greatly expanding the applicability of the
reaction. Subsequently, a scope of iodobenzenes was per-
formed. Iodobenzenes with electron-donating substituent
show excellent reactivity, afforded the corresponding prod-
ucts in excellent yields (4a–4 f). In addition, iodoarenes
substituted with electron-withdrawing group such as Cl and
CF3 groups were also tolerated in this process, delivered the
desired products in moderate yields (4g–4j). Functional
groups, such as amide (4n), indole (4o, 4q), pyridine (4p),
morphine (4r) and Bpin (4t) were all compatible in this
transformation. PhN2BF4, PhBr, and PhOTf was tested
instead of PhI was well, but no desired product could be
detected. More complexed substrates were successfully trans-
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Table 2: Substrate scope of gem-difluoroalkenes and iodobenzenes.[a]
[a] Reaction conditions: gem-difluoroalkenes (0.2 mmol), iodobenzenes (1.2 equiv), CuCl (10 mol%), PdCl2 (2 mol%), DPPP (4 mol%), B2pin2
(1.0 equiv), LiOMe (3.0 equiv), CO (10 bar), DMAc (0.2 M), 608C, 20 h, isolated yields.
formed under our standard conditions as well, delivered the
gem-difluoroalkenes failed to deliver the corresponding
target products in moderate to good yields (5a–5d). Aliphatic
product (see supporting information for more details).
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In order to further demonstrate the synthetic value of this
target product was not formed neither and trace protode-
procedure, transformations of a-fluorochalcone were carried
out (Scheme 3).[15] a-Fluorochalcone can be transformed into
3,5-disubstituted phenols 6a in an one-pot manner.[15a]
Furthermore, a-fluorochalcone can be reduced to alkyl
alcohol 6b or allyl alcohol 6c under Pd/H2 or NaBH4
conditions. In addition, a-allyl alcohol can be further trans-
formed into a-fluoroallyl amine 6d/6d’ and a-fluoroallyl
ether 6e in moderate yields. Good stereoselectivity were
observed in these cases.
For a better mechanistic understanding of this Pd/Cu
catalyzed defluorinative carbonylation, several control
experiments were performed (Scheme 4). Since we observed
Z-fluorinated vinylboronate ester 3a’ in this transformation,
we are wondering whether 3a’ acts as an intermediate of the
reaction. Therefore, 3a’ was prepared and subjected to the
standard conditions, the desired product 3a was not observed;
instead, we detected 95% yield of protodeboronation product
7c. Moreover, in the case of absence of B2pin2/CuCl, the
fluorination product 7b was obtained [Scheme 4, Eq. (a)]. In
addition, 3a’ and benzoyl chloride failed to deliver the target
product which further ruled out 3a’ as the reaction inter-
mediate [Scheme 4, Eq. (b)]. No desired product could be
detected when phenyl borate 7d was tested with or without
B2pin2 [Scheme 4, Eq. (c)]. These results of the experiments
indicate that 3a’ and 7d were not intermediates of the
reaction. Therefore, the possibility of cascade processes seems
to be ruled out. Subsequently, we speculated 7e might be the
intermediate of the reaction. Surprisingly, when 7e was
subject to this defluorinative carbonylation, the product 7 f
was delivered in 40% yield under our standard conditions
(Table 3). CO/B2pin2 were proven to be necessary for this
process. This leads to the conclusion that alkene which inserts
into the acyl-PdIIX species.
Based on the above experimental results and related
literatures,[4–10] we proposed a possible reaction pathway for
this transformation (Scheme 5). The catalytic cycle consists of
two individual cycles involving copper and palladium cata-
lysts. In the palladium cycle, under the reduction of phosphine
ligand, catalytically active LPd0 complex can be produced in
situ. Oxidative addition of aryl iodide to LPd0, followed by
CO coordination and insertion, leads to the key acyl-PdIII
intermediate A. Subsequently, the alkyl-PdIII species B was
formed after a migratory insertion into the double bond.
Afterwards, the alkyl-PdIII complex B reacts with CuBpin
Table 3: Mechanistic study.
Scheme 3. Derivatization of a-fluorochalcone. Reaction conditions:
a) ethyl 2-fluoro-3-oxobutanoate, Cs2CO3, MeCN, 1208C, 4 h. b) Pd/C,
H2 (1 bar) EtOH/THF, rt, 12 h. c) NaBH4 MeOH, rt, 0.5 h. d) PPh3,
imide, DIAD, THF, rt, 3 h. e) NaH, BnBr, Bu4NI, THF, rt, 5 h.
Entry
Variations from standard conditions
Yield [%]
1
2
3
4
5
none
w/o B2pin2
w/o CO
w/o CuCl
w/o PdCl2 and DPPP
40
0
0
<5
<5
Scheme 4. Control experiments.
Scheme 5. Plausible reaction mechanism.
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Zhu, C. Feng, T. P. Loh, Chem. Commun. 2017, 53, 8731 – 8734;
d) P. Tian, C. Feng, T.-P. Loh, Nat. Commun. 2015, 6, 7472; e) J.
Hu, X. Han, Y. Yuan, Z. Shi, Angew. Chem. Int. Ed. 2017, 56,
13342 – 13346; Angew. Chem. 2017, 129, 13527 – 13531; f) R. T.
Thornbury, F. D. Toste, Angew. Chem. Int. Ed. 2016, 55, 11629 –
11632; Angew. Chem. 2016, 128, 11801 – 11804; g) J. Xie, J. Yu,
M. Rudolph, F. Rominger, A. S. Hashmi, Angew. Chem. Int. Ed.
2016, 55, 9416 – 9421; Angew. Chem. 2016, 128, 9563 – 9568; h) Y.
Xiong, T. Huang, X. Ji, J. Wu, S. Cao, Org. Biomol. Chem. 2015,
13, 7389 – 7392; i) R. Kojima, K. Kubota, H. Ito, Chem.
Commun. 2017, 53, 10688 – 10691; j) N. O. Andrella, N. Xu,
B. M. Gabidullin, C. Ehm, R. T. Baker, J. Am. Chem. Soc. 2019,
141, 11506 – 11521; k) H. Sakaguchi, Y. Uetake, M. Ohashi, T.
Niwa, S. Ogoshi, T. Hosoya, J. Am. Chem. Soc. 2017, 139, 12855 –
12862; l) H. W. Du, J. Sun, Q. S. Gao, J. Y. Wang, H. Wang, Z.
Xu, M. D. Zhou, Org. Lett. 2020, 22, 1542 – 1546; m) A. Kondoh,
K. Koda, M. Terada, Org. Lett. 2019, 21, 2277 – 2280; n) J. Zhang,
W. Dai, Q. Liu, S. Cao, Org. Lett. 2017, 19, 3283 – 3286; o) Q. Ma,
C. Liu, G. C. Tsui, Org. Lett. 2020, 22, 5193 – 5197; p) Q. Ma, Y.
Wang, G. C. Tsui, Angew. Chem. Int. Ed. 2020, 59, 11293 – 11297;
Angew. Chem. 2020, 132, 11389 – 11393; q) T. Fujita, K. Fuchibe,
J. Ichikawa, Angew. Chem. Int. Ed. 2019, 58, 390 – 402; Angew.
Chem. 2019, 131, 396 – 408.
species via transmetalation to give intermediate C; CuBpin
was generated from LiOMe, B2pin2 and CuX in the copper
cycle. Promoted by boron, intermediate C undergoes b-
fluoride elimination to deliver the desired a-fluorochalcone
with only Z-isomer and regenerate the catalytically active
LPd0 catalyst after reductive elimination.
In summary, we have developed the first example on
defluorinative carbonylation. Catalyzed by Pd/Cu co-cata-
lysts, the carbonylative cross-coupling between aryl iodides
and gem-difluoroalkenes occurred. A variety of valuable a-
fluorochalcones were obtained in good yields under mild
conditions. Diverse functional group were well tolerated in
this process. Synthetic transformations of the obtained a-
fluorochalcones product clearly demonstrate the value of this
process.
Acknowledgements
We thank the China Scholarship Council for a Ph.D. Scholar-
ship. We appreciate the analytical department of the Leibniz-
Institute for Catalysis at the University of Rostock for their
assistance.
[8] Recent example: a) Z. Lin, Y. Lan, C. Wang, ACS Catal. 2019, 9,
775 – 780; b) T. Ma, Y. Chen, Y. Li, Y. Ping, W. Kong, ACS Catal.
2019, 9, 9127 – 9133; c) J. Li, W. Rao, S.-Y. Wang, S.-J. Ji, J. Org.
Chem. 2019, 84, 11542 – 11552.
[9] Recent example: a) S.-S. Yan, D.-S. Wu, J.-H. Ye, L. Gong, X.
Zeng, C.-K. Ran, Y.-Y. Gui, J. Li, D.-G. Yu, ACS Catal. 2019, 9,
6987 – 6992; b) J. Liu, W. Nie, H. Yu, J. Shi, Org. Biomol. Chem.
2020, 18, 9065 – 9071.
Conflict of interest
[10] a) X.-F. Wu, H. Neumann, M. Beller, Chem. Rev. 2013, 113, 1 –
35; b) J.-B. Peng, F.-P. Wu, X.-F. Wu, Chem. Rev. 2019, 119,
2090 – 2127; c) Y. Li, Y. Hu, X.-F. Wu, Chem. Soc. Rev. 2018, 47,
172 – 194.
The authors declare no conflict of interest.
Keywords: carbonylation · copper · coupling reactions ·
palladium · a-fluorochalcones
À
[11] Selective reviews and examples of C F bond activation: a) H.
Amii, K. Uneyama, Chem. Rev. 2009, 109, 2119 – 2183; b) T.
Ahrens, J. Kohlmann, M. Ahrens, T. Braun, Chem. Rev. 2015,
115, 931 – 972; c) M. Ohashi, H. Saijo, M. Shibata, S. Ogoshi, Eur.
J. Org. Chem. 2013, 443 – 447.
[1] a) W. K. Hagmann, J. Med. Chem. 2008, 51, 4359 – 4369; b) K.
Muller, C. Faeh, F. Diederich, Science 2007, 317, 1881 – 1886;
c) T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed.
2013, 52, 8214 – 8264; Angew. Chem. 2013, 125, 8372 – 8423.
[2] a) Y. Asahina, K. Iwase, F. Iinuma, M. Hosaka, T. Ishizaki, J.
Med. Chem. 2005, 48, 3194 – 3202; b) S. Couve-Bonnaire, D.
Cahard, X. Pannecoucke, Org. Biomol. Chem. 2007, 5, 1151 –
1157; c) C. E. Jakobsche, A. Choudhary, S. J. Miller, R. T.
Raines, J. Am. Chem. Soc. 2010, 132, 6651 – 6653; d) S. Osada,
S. Sano, M. Ueyama, Y. Chuman, H. Kodama, K. Sakaguchi,
Bioorg. Med. Chem. 2010, 18, 605 – 611.
[12] J. Vela, J. Smith, Y. Yu, N. Ketterer, C. Flaschenriem, R.
Lachicotte, P. Holland, J. Am. Chem. Soc. 2005, 127, 7857 – 7870.
[13] a) X.-F. Wu, H. Neumann, A. Spannenberg, T. Schulz, H. Jiao,
M. Beller, J. Am. Chem. Soc. 2010, 132, 14596 – 14602; b) X.-F.
Wu, H. Neumann, M. Beller, Angew. Chem. Int. Ed. 2010, 49,
5284 – 5288; Angew. Chem. 2010, 122, 5412 – 5416; c) J. Schranck,
X.-F. Wu, H. Neumann, M. Beller, Chem. Eur. J. 2012, 18, 4827 –
4831; d) K. S. Bloome, E. J. Alexanian, J. Am. Chem. Soc. 2010,
132, 12823 – 12825; e) M. K. Brennaman, A. O. T. Patrocinio, W.
Song, J. W. Jurss, J. J. Concepcion, P. G. Hoertz, M. C. Traub,
N. Y. Murakami Iha, T. J. Meyer, ChemSusChem 2011, 4, 216 –
227; f) X.-F. Wu, H. Neumann, M. Beller, Chem. Asian J. 2012, 7,
282 – 285.
[14] a) “Peptidomimetics”: G. Klebe in Drug Design (Eds.: G.
Klebe), Springer, Berlin, 2013; b) R. S. H. Liu, H. Matsumoto,
A. E. Asato, M. Denny, Y. Shichida, T. Yoshizawa, F. W.
Dahlquist, J. Am. Chem. Soc. 1981, 103, 7195 – 7201.
[15] a) J. Qian, W. Yi, X. Huang, Y. Miao, J. Zhang, C. Cai, W. Zhang,
Org. Lett. 2015, 17, 1090 – 1093; b) Y. Bessiꢁre, D. N.-H. Savary,
M. Schlosser, Helv. Chim. Acta 1977, 60, 1739 – 1746; c) T.
Allmendinger, P. Furet, E. Hungerbꢀhler, Tetrahedron Lett.
1990, 31, 7297 – 7300; d) T. Allmendinger, E. Felder, E. Hun-
garbꢀhler, Tetrahedron Lett. 1990, 31, 7301 – 7304.
[3] a) G. Landelle, M. Bergeron, M. O. Turcotte-Savard, J. F.
Paquin, Chem. Soc. Rev. 2011, 40, 2867 – 2908; b) H. Yanai, T.
Taguchi, Eur. J. Org. Chem. 2011, 5939 – 5954.
[4] Recent reviews on synthesis of gem-difluoroalkenes: a) X.
Zhang, S. Cao, Tetrahedron Lett. 2017, 58, 375 – 392; b) C. Liu,
H. Zeng, C. Zhu, H. Jiang, Chem. Commun. 2020, 56, 10442 –
10452; c) S. Koley, R. A. Altman, Isr. J. Chem. 2020, 60, 313–339.
[5] X. Lu, Y. Wang, B. Zhang, J. J. Pi, X. X. Wang, T. J. Gong, B.
Xiao, Y. Fu, J. Am. Chem. Soc. 2017, 139, 12632 – 12637.
[6] Recent examples, see: a) M. Ohashi, R. Kamura, R. Doi, S.
Ogoshi, Chem. Lett. 2013, 42, 933 – 935; b) W. Dai, H. Shi, X.
Zhao, S. Cao, Org. Lett. 2016, 18, 4284 – 4287; c) J. Zhang, C. Xu,
W. Wu, S. Cao, Chem. Eur. J. 2016, 22, 9902 – 9908; d) Z. S. Cong,
Y. G. Li, L. Chen, F. Xing, G. F. Du, C. Z. Gu, L. He, Org.
Biomol. Chem. 2017, 15, 3863 – 3868.
[7] Recent examples, see: a) L. Kong, X. Zhou, X. Li, Org. Lett.
2016, 18, 6320 – 6323; b) D. Zell, U. Dhawa, V. Mꢀller, M.
Bursch, S. Grimme, L. Ackermann, ACS Catal. 2017, 7, 4209 –
4213; c) S. H. Cai, L. Ye, D. X. Wang, Y. Q. Wang, L. J. Lai, C.
Manuscript received: December 31, 2020
Accepted manuscript online: February 4, 2021
Version of record online: March 9, 2021
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