Deoxygenation of Ethers to Form Carbon-Carbon Bonds via Nickel Catalysis

Article abstract of DOI:10.1021/jacs.7b02326

In this article a successful protocol was developed to construct carbon-carbon bonds by the extrusion of the O atom of ethers via nickel catalysis in the presence of reductants. This methodology is featured as a highly economic route to construct sp³-sp³ C-C bonds through dual C-O activation of ethers with good functional group tolerance.

Full text of DOI:10.1021/jacs.7b02326

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Communication
Deoxygenation of Ethers to Form Carbon-Carbon Bonds via Nickel Catalysis
Zhi-Chao Cao, and Zhang-Jie Shi
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 26 Apr 2017
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Deoxygenation of Ethers to Form Carbon-Carbon Bonds via Nickel
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Catalysis
ZhiꢀChao Cao,a ZhangꢀJie Shi*a,b
a College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 and b Department of Chemistry, Fuꢀ
dan University, Shanghai 200433, and State Key Laboratory of Organometallic Chemistry, Chinese Academy of Science,
Shanghai 200032, China
Supporting Information Placeholder
our knowledge, there was no sufficient route of reductive couꢀ
pling between two etheric CꢀO electrophiles presented, espeꢀ
ABSTRACT: In this article a successful protocol was developed
to construct carbonꢀcarbon bonds by the extrusion of Oꢀatom of
ethers via nickel catalysis in the presence of reductants. This
methodology featured as a high economic route to construct sp3ꢀ
sp3 CꢀC bonds through dual CꢀO activation of ethers with good
functional group tolerance.
5k
cially the proposed deoxygenation of acyclic ethers to date.6
Compared to the developed reductive couplings, the deoxygenaꢀ
tion of ethers faces the following predictable challenges: 1) the
cleavage of both CꢀO bonds of ethers at different stages under the
same conditions, especially the CꢀO bond in the formed alkoxide
CꢀO bonds at the latter stage; 2) the proper Oꢀacceptor to remove
the oxygen atom from the ethers.
Table 1, Effects of ligands in deoxygenation reactions a
Ethers used as partners in crossꢀcouplings exhibited a myriad of
advantages due to their easy availability, stability, and nonꢀ
toxicity. Recently, efforts to explore the potential utility of ethers,
especially aryl ethers1 and benzyl ethers2, in cross couplings via
transitionꢀmetal catalysis, have been made. However, in develꢀ
oped cross couplings with ethers, only one part of ether was used
and the rest part was discarded with the second CꢀO bond unꢀ
touched, to some extent showing the undesirable carbon atom
economy (Scheme 1a).3 To solve this problem, our recent focuses
were set out to develop new protocols to apply both parts of ethers
into organic synthesis through activation of both CꢀO bonds in
one reaction. From this point of view, the deoxygenation of ethers
to construct CꢀC bonds is an ideal choice, which was fundamenꢀ
tally important to investigate the activation of both etheric CꢀO
bonds at different stages under the same conditions (Scheme 1b).
NiBr2 glyme) (10 mol%)
ligand
2
O
2
Zn (2.5 equiv), B2pin2 (1.0 equiv)
PhMe/THF (1:1), 115 C, 12 h
1a
PPh3
2a
PCy3
Ph2P
PPh2
L1 (40 mol%), 0%
L2 (40 mol%), 0%
L3, DPPM (20 mol%), 0%
Cy2P
PCy2
L5, DPPPr (20 mol%), 0% L6, DCPPr (20 mol%), 0%
PPh2
Ph2P
Ph2P
PPh2
L4, DPPE (20 mol%), 0%
PPh2
Ph2P
PCy2
O
Cy2P
O
PPh2
Ph2P
L7, DPPB (20 mol%), 78% (75%)
L8, DCPB (20 mol%), 0%
L9 (20 mol%), 0%
PPh2
PPh2
PPh2
PCy2
Ph2P
Cy2P
L10 (20 mol%), 0%
L11 (20 mol%), 0%
L12 (20 mol%), 22%
H
N
Ph2P
PPh2
O
O
PPh2
PPh2
PPh2
PPh2
L13, DPPPent (20 mol%), 49%
L14, Xantphos (20 mol%), 33%
L15 (20 mol%), 0%
Reaction conditions: a cocktail containing substrate 1a (0.1
mmol), catalyst NiBr2(glyme) (0.01 mmol), ligand, zinc dust (0.25
mmol), B2pin2 (0.1 mmol) in PhMe/THF (1:1) was heated at 115
a
oC for 12 h. NMR yields were reported based on 1a, and benꢀ
zo[d][1,3]dioxole was used as an internal standard; isolated yields
of desired product was reported in parenthesis.
Scheme 1, Design of reductive deoxygenation of ethers
To interview our concept, we chose 2,2'ꢀoxybis(methylene)ꢀ
dinaphthalene (1a) as the objective to investigate the designed
deoxygenation. According to previous works in CꢀO activation
and reductive coupling, Niꢀcatalysis was first considered in the
presence of different ligand sets. As analyzed above, the proper
reductant is required to provide the electrons to facilitate the reꢀ
Our strategy toward the deoxygenation was based on the reductive
couplings, which have been developed as powerful methods to
construct carbonꢀcarbon bonds.4 At current stage, the reductive
coupling was used to carry out the transformation of organohalꢀ
ides. Recently, sporadic cases to elucidate the reductive coupling
of ethers with organohalides were also reported.5 To the best of
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duction. The Oꢀreceptor was also demanded to remove the Oꢀ
tolerated, which provided another chance to diversify the products
through nickel catalyzed cross couplings2, 9 (2g, 2h and 2l). Subꢀ
strate bearing cyano group also exhibited moderate reactivity
under standard conditions (2k). At last, this deoxygenation also
proceeded smoothly with the steric hindered orthoꢀsubstituent
ethers (2l and 2m), albeit in lower yields. Unfortunately, this cataꢀ
lytic system is unable to facilitate the reductive deoxygenation of
simple dibenzyl ethers at this stage, even the ethers with electron
withdrawing group (2n) or directing group (2o) at the orthoꢀ
position.
atom in the ethers. In previous reports, metal powder was usually
used in "reductive coupling" as electron donor and halogen scavꢀ
enger.5 We also tested different metal powder. After systematical
examination of different parameters, such as nickel catalysts,
ligands, reductants, and solvents, to our delight, the desired prodꢀ
uct 1,2ꢀdinaphthylethane 2a was obtained in 17% NMR yield
when 10 mol% NiBr2(glyme) was used as the catalyst in the presꢀ
ence of DPPB as the ligand and zinc powder as an reductant (Ta-
ble S1 and S2).
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Considering the poor capability of zinc as an Oꢀscavenger, B2pin2
(1.0 equiv) was used as the additive. To our satisfactory, the deꢀ
sired product (2a) was obtained in 75% isolated yield. Due to the
Lewis acidity of B2pin2, it might be beneficial for reorganizing
electron density of CꢀO bond of the ethers and also facilitating the
2nd oxidative addition by coordination. Other lewis acids, such as
AlCl3 and B2nep2, were tested but failed. This result indicated
other effect of B2pin2 than a simple Lewis acid7 (Table S2).
In the presence Zn and B2pin2, the effect of ligand was further
systematically investigated (Table 1). Monodentate phosphine
ligands, including PCy3 (L2), which exhibited excellent reactivity
to promote the CꢀO activation in nickel catalysis, were not effecꢀ
tive. Various bidentate phosphine ligands with different bite anꢀ
gles were submitted to the catalytic transformation, and the results
indicated that bidentate phosphine ligands with large bite angle
promote the efficiency8 (L3ꢀL7 and L13). For example, DPPB
(L7) promoted the desired product 2a formation in 78% NMR
yield; only 49% NMR yield was obtained when DPPent (L13)
was employed as the ligand. Furthermore, variants of DPPB and
DPPent, such as more electronꢀefficient DCPB (L8), more rigid
ligands (L9ꢀL12 and L14ꢀL15) were tested. Unfortunately, none
of them showed the better reactivity.
To further explore the potential applications, we conducted the
reductive deoxygenation of substrates containing heterocycles.
Both 2,2'ꢀoxybis(methylene)dibenzofuran (1p) and 2,2'ꢀ
oxybis(methylene)dibenzo[b]thiophene (1q) gave the desired
products in good yields (2p and 2q) (Eq 1). It is worth noting that
product 2r was obtained via the deoxygenation of highly steric
hindered 1r under the standard conditions in an acceptable yield
(Eq 2). While, βꢀH elimination occurred in the presence of a meꢀ
thyl group at the αꢀposition of ether and the desired product 2s
was not observed.
Table 2, Reductive Deoxygenation of dibenzyl ethers a
Beside symmetric ethers, asymmetric ether 1t was submitted to
this catalytic system and the product 2t was obtained as the major
product in 40% yield, while byꢀproducts 2a and 2g were observed
in lower yields. The similar phenomenon was also observed in the
deoxygenation of 1u. This result indicated that this reaction occur
in an intermolecular manner (Eq 3).
During the deoxygenation, a small amount of 2ꢀnapththylmethyl
boronate was observed by GCꢀMS. In fact, the borylation of benꢀ
zyl ethers were reported during we conducted these studies.2k, 10
To gain insight into the mechanism, we carefully reviewed the
reaction system and conducted the additional experiments
(Scheme 2). As mentioned above, in the absence of B2pin2, the
desired product 2a was indeed observed albeit in a low yield (17%
NMR yield) (Eq. 4). This result clearly demonstrated the catalytꢀ
ic pathway could proceed in the absence of any Bꢀbased intermeꢀ
diates. To further understand the roles of the possible benzylꢀ
boronate in the catalytic cycle, prepared aryl methyl boronate (2.0
equiv) was added in this deoxygenation (Eq 5).11 To our surprise,
the additional naphthylmethyl boronate 5 was recovered in more
than 80% yield (the rest part was protonated to methylarene). The
cross coupling product between 1g and 5 was detected in trace
amount by both the crude 1H NMR spectra and GCꢀMS. This
result ruled out the participation of benzylboronate as a key inꢀ
termediate in the catalytic cycle. It is important to note that, the
additional benzylboronate suppressed this transformation and the
yields of desired products were severely decreased.
Reaction conditions: a cocktail contain substrate 1 (0.1 mmol),
catalyst NiBr2(glyme) (0.01 mmol), ligand, zinc dust (0.25 mmol),
o
B2pin2 (0.1 mmol) in PhMe/THF (1:1) was heated at 115 C for
12 h. a isolated yields were reported based on 1; b NMR yield.
Subsequently, the optimal conditions were applied to the deoxyꢀ
genation of various diarylmethyl ethers (Table 2). First of all, we
tested the effect of substitutions on the naphthyl ring and found
that, both electronꢀdonating and electronꢀwithdrawing substituents
did not affect the efficiency (2aꢀj). The substrates bearing differꢀ
ent alkyl groups converted to the corresponding targeted products
in good to excellent yields. Moreover, cyclopropyl group (1f)
survived well. The experiments to test the tolerance of sp2 CꢀO
and CꢀN bonds were conducted. Notably, various groups were
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a. Control experiments (Eq 4)
NiBr2 glyme) (10 mol%)
DPPB (20 mol%)
B2pin2 (1.0 equiv)
Zn (2.5 equiv)
the reductant Zn was not only involved into the catalytic cycles at
the initiate stage.
O
PhMe/THF (1:1)
115 C, 12 h
1a (0.1 mmol)
2a
Yield of 2a: 17% in the absence of B2pin2; 0% in the absence of Zn
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b. Deoxygenation of 1g in the presence of NpCH2Bpin 5 (Eq 5)
standard
conditions
2O
Bpin
2g
(3%)
2p
2a
+
+
+
(< 0.5%) (< 0.5%)
MeO
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1g, 0.1 mmol
5, 0.2 mmol (85% recovery)
c. Deoxygenation of 1g in the presence of NpCH2ZnBr 6 (Eq 6)
standard
2O
ZnBr conditions
2g
(8%)
2p
(27%)
2a
(42%)
+
+
+
MeO
1g, 0.1 mmol
d. Deoxygenation of 1g in the presence of Mn (Eq 7)
NiBr2 glyme) (10 mol%)
6, 0.2 mmol
DPPB (20 mol%)
B2pin2 (1.0 equiv)
Mn (2.5 equiv)
PhMe/THF (1:1)
115 C, 12 h
O
1a (0.1 mmol)
2a (59%)
e. Deoxygenation of 1a in the presence of Ni(cod)2 + DPPB + Zn + B2pin2 (Eq 8)
Ni(cod)2 (10 mol%)
DPPB (20 mol%)
Zn (2.5 equiv)
B2pin2 (1.0 equiv)
PhMe/THF (1:1)
115 C, 12 h
Scheme 3, Proposed mechanism of deoxygenation of ethers
O
On the basis of the current results and previous reports, a plausiꢀ
ble mechanism was depicted in Scheme 3. First of all, the nickꢀ
el(II) species II was formed via the first oxidative addition of
ether toward Ni(0) species, which was reduced to the nickel(I)
species III by zinc14. Subsequently, the second oxidative addition
of another CꢀO bonds took place on the Ni(I) species to form the
Ni(III) species. Indeed, the proper reductant was very important to
reduce the formed Ni(II) species. Since the difficulty to form the
carbonꢀcentered radical via the homo session of etheric CꢀO
bond15, this oxidative addition probably took place through a conꢀ
certed or SN2 pathway, which should be different from the reportꢀ
ed radical pathway.5 Finally, the desired product released through
sp3ꢀsp3 carbonꢀcarbon bond reductive elimination on nickel (III)
central to regenerate Ni(I) species. Such a Ni(I) species was furꢀ
ther reduced to Ni(0) by zinc to fulfill the catalytic cycle, thus
showing the second role of the reductant. During this catalytic
cycle, B2pin2 probably played a key role as a Lewis acid to proꢀ
mote the reactivity of the ethers and in-situ generated alkoxide as
well as the oxygen scavenger although other possibilities could
not be rooted out at this stage.7
1a (0.1 mmol)
2a (78%)
f. Deoxygenation of 1a in the presence of Ni(cod)2 + DPPB (Eq 9)
Ni(cod)2 (1.0 equiv)
O
DPPB (2.0 equiv)
PhMe/THF (1:1)
115 C, 12 h
1a (0.1 mmol) (92% recovery)
2a (0%)
g. Deoxygenation of 1a in the presence of Ni(cod)2 + DPPB + B2pin2 (Eq 10)
Ni(cod)2 (1.0 equiv)
DPPB (2.0 equiv)
B2pin2 (1.0 equiv)
PhMe/THF (1:1)
115 C, 12 h
O
1a (0.1 mmol) (> 95% recovery)
2a (0%)
Scheme 2, Mechanism studies
To unveil the role of benzyl zinc reagent in catalytic cycle, we
conducted the deoxygenation reaction of 1g in the presence of
prepared benzylzinc 6 (Eq 6), the desired product 2g was formed
in only 8% yield. In this catalytic system, a coupling product beꢀ
tween 1g and 6 was observed in 27%. Furthermore, Mn was used
to instead of Zn as the reductant to promote the deoxygenation of
1a, and the target product was prepared in 59% yield (Eq 7).
Combining with the capturing experiments, we ruled out the role
of benzyl zinc reagent as an intermediate in catalytic cycle (see SI
for details).
In summary, we for the first time developed the method to syntheꢀ
size 1,2ꢀdiarylethanes via direct deoxygenation of diarylmethyl
ethers. Challenges in this transformation were conquered toward
the extrusion of oxygen of ethers. This chemistry exhibited good
atomꢀ and stepꢀ economy and offered a complementary strategy in
organic synthesis to produce Cꢀbased skeletons from Oꢀlinked
molecules.
To further elucidate the mechanism, other control experiments
were performed (Eq 8-10). In the absence of the reductant Zn, the
deoxygenation reaction was terminated despite in the presence of
a stoichiometric amount of Ni(cod)2. Obviously, zinc played an
essential role to fulfill the whole catalytic cycle. On the other
hand, this result also indicated that the product was unlikely furꢀ
nished via the transmetallation of two Ni(II) species II, which was
generated from the first oxidative addition. Meanwhile, the recovꢀ
ery of 1a indicated that the oxidative addition of CꢀO bond to
Ni(0) could not occur in the absence of Zn.12 Moreover, this result
also excluded the formation of Ni(IV) species in this catalytic
reaction through double sequential oxidative addition of two types
of CꢀO bonds from Ni(0) species (See SI for details). Otherwise,
the coupling could take place in the presence of stoichiometric
Ni(0) species and in the absence of any reductants.13 Obviously,
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Experimental procedures and characterization data of products
PDF
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: zshi@pku.edu.cn, zjshi@fudan.edu.cn
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ton Trans. 2003, 1890; (c) van Leeuwen, P. W. N. M.; Kamer, P. C. J.;
Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741.
(9) Tobisu, M.; Nakamura, K.; Chatani, N. J. Am. Chem. Soc. 2014,
136, 5587.
(10) (a) Kinuta, H.; Tobisu, M.; Chatani, N. J. Am. Chem. Soc. 2015,
137, 1593; for case on Pdꢀcatalyzed CꢀO bond borylation: (b) Cao, Z.ꢀC.;
Luo, F.ꢀX.; Shi, W.ꢀJ.; Shi, Z.ꢀJ. Org. Chem. Front. 2015, 2, 1505; for
case on Niꢀcatalyzed CꢀO bond borylation: ref. 2k.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
Support of this work by the “973” Project from the MOST
(2015CB856600 and 2013CB228102) and NSFC (Nos. 21332001
and 21431008) is gratefully acknowledged. Thanks XiaoꢀLei Li
and PeiꢀLing Xu (both in Peking University) for the assistance of
melting point measurement.
8
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(11) Tellis, J. C.; Primer, D. N.; Molander, G. A. Science 2014, 345,
433.
(12) The ZnBr2 generated in the reduction of high valent nickel species
could be acting as a Lewis acid, lowering down the barrier for oxidative
addition.
(13) In this cases, if reductant is not essential, desired product can be
observed and the yield equal to the loading of catalyst.
(14) (a) Dauth, A.; Love, J. A. Dalton Transactions 2012, 41, 7782; (b)
Horvath, S.; Fernandez, L. E.; Appel, A. M.; HammesꢀSchiffer, S. Inorg.
Chem. 2013, 52, 3643.
(15) Diéguez, H. R.; López, A.; Domingo, V.; Arteaga, J. F.; Dobado, J.
A.; Herrador, M. M.; Quílez del Moral, J. F.; Barrero, A. F. J. Am. Chem.
Soc. 2010, 132, 254; and ref. 5a and 5b.
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REFERENCES
(1) (a) Wenkert, E.; Michelotti, E. L.; Swindell, C. S. J. Am. Chem.
Soc. 1979, 101, 2246; (b) Dankwardt, J. W. Angew. Chem. Int. Ed. 2004,
43, 2428; (c) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J.
Am. Chem. Soc. 2004, 126, 2706; (d) Tobisu, M.; Shimasaki, T.; Chatani,
N. Angew. Chem. Int. Ed. 2008, 47, 4866; (e) Tobisu, M.; Shimasaki, T.;
Chatani, N. Chem. Lett. 2009, 38, 710; (f) ÁlvarezꢀBercedo, P.; Martin, R.
J. Am. Chem. Soc. 2010, 132, 17352; (g) Sergeev, A. G.; Hartwig, J. F.
Science 2011, 332, 439; (h) Kelley, P.; Lin, S.; Edouard, G.; Day, M. W.;
Agapie, T. J. Am. Chem. Soc. 2012, 134, 5480; (i) Cornella, J.; Gómezꢀ
Bengoa, E.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1997; (j) Leiendeckꢀ
er, M.; Hsiao, C.ꢀC.; Guo, L.; Alandini, N.; Rueping, M. Angew. Chem.
Int. Ed. 2014, 53, 12912; (k) Cong, X.; Tang, H.; Zeng, X. J. Am. Chem.
Soc. 2015, 137, 14367; (l) Tobisu, M.; Takahira, T.; Ohtsuki, A.; Chatani,
N. Org. Lett. 2015, 17, 680; (m) Zarate, C.; Manzano, R.; Martin, R. J. Am.
Chem. Soc. 2015, 137, 6754; (n) Liu, X.; Hsiao, C.ꢀC.; Kalvet, I.;
Leiendecker, M.; Guo, L.; Schoenebeck, F.; Rueping, M. Angew. Chem.
Int. Ed. 2016, 55, 6093; (o) Guo, L.; Liu, X.; Baumann, C.; Rueping, M.
Angew. Chem. Int. Ed. 2016, 55, 15415; (p) Tobisu, M.; Takahira, T.;
Morioka, T.; Chatani, N. J. Am. Chem. Soc. 2016, 138, 6711.
(2) (a) Guan, B.ꢀT.; Xiang, S.ꢀK.; Wang, B.ꢀQ.; Sun, Z.ꢀP.; Wang, Y.;
Zhao, K.ꢀQ.; Shi, Z.ꢀJ. J. Am. Chem. Soc. 2008, 130, 3268; (b) Taylor, B.
L. H.; Swift, E. C.; Waetzig, J. D.; Jarvo, E. R. J. Am. Chem. Soc. 2011,
133, 389; (c) Taylor, B. L. H.; Harris, M. R.; Jarvo, E. R. Angew. Chem.
Int. Ed. 2012, 51, 7790; (d) Tollefson, E. J.; Dawson, D. D.; Osborne, C.
A.; Jarvo, E. R. J. Am. Chem. Soc. 2014, 136, 14951; (e) Harris, M. R.;
Konev, M. O.; Jarvo, E. R. J. Am. Chem. Soc. 2014, 136, 7825;.
(3) (a) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A.ꢀM.; Garg, N. K.; Percec, V. Chem. Rev. 2010, 111, 1346; (b)
Yu, D.ꢀG.; Li, B.ꢀJ.; Shi, Z.ꢀJ. Acc. Chem. Res. 2010, 43, 1486; (c) Li, B.
J.; Yu, D. G.; Sun, C. L.; Shi, Z. J. Chem. Eur. J. 2011, 17, 1728; (d)
Cornella, J.; Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43, 8081; (e) Su,
B.; Cao, Z.ꢀC.; Shi, Z.ꢀJ. Acc. Chem. Res. 2015, 48, 886; (f) Tobisu, M.;
Chatani, N. Acc. Chem. Res. 2015, 48, 1717; (g) Tollefson, E. J.; Hanna, L.
E.; Jarvo, E. R. Acc. Chem. Res. 2015, 48, 2344.
(4) (a) Czaplik, W. M.; Mayer, M.; JacobivonWangelin, A. Angew.
Chem. Int. Ed. 2009, 48, 607; (b) Everson, D. A.; Shrestha, R.; Weix, D. J.
J. Am. Chem. Soc. 2010, 132, 920; (c) Qian, X.; Auffrant, A.; Felouat, A.;
Gosmini, C. Angew. Chem. Int. Ed. 2011, 50, 10402; (d) Knappke, C. E. I.;
Grupe, S.; Gartner, D.; Corpet, M.; Gosmini, C.; Jacobi von Wangelin, A.
Chem. Eur. J. 2014, 20, 6828; (e) Everson, D. A.; Weix, D. J. J. Org.
Chem. 2014, 79, 4793; (f) Gu, J.; Wang, X.; Xue, W.; Gong, H. Org.
Chem. Front. 2015, 2, 1411; (g) Weix, D. J. Acc. Chem. Res. 2015, 48,
1767; (h) Kadunce, N. T.; Reisman, S. E. J. Am. Chem. Soc. 2015, 137,
10480; (i) Wang, X.; Wang, S.; Xue, W.; Gong, H. J. Am. Chem. Soc.
2015, 137, 11562; (j) Ackerman, L. K. G.; Lovell, M. M.; Weix, D. J.
Nature 2015, 524, 454; (k) Iranpoor, N.; Panahi, F. Org. Lett. 2015, 17,
214.
(5) (c) Tollefson, E. J.; Erickson, L. W.; Jarvo, E. R. J. Am. Chem. Soc.
2015, 137, 9760; for selected example on crossꢀelectrophileꢀcoupling on
aryl ethers with aryl halides: Cao, Z.ꢀC.; Luo, Q.ꢀY.; Shi, Z.ꢀJ. Org. Lett.
2016, 18, 5978.
(6) Nakamura, K.; Tobisu, M.; Chatani, N. Org. Lett. 2015, 17, 6142.
(7) Xu, H.; Zhao, C.; Qian, Q.; Deng, W.; Gong, H. Chem. Sci. 2013, 4,
4022.
(8) (a) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc.
Chem. Res. 2001, 34, 895; (b) Freixa, Z.; van Leeuwen, P. W. N. M. Dal-
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