Functionalized Polymer-Supported Pyridine Ligands for Palladium-Catalyzed C(sp3)-H Arylation

Article abstract of DOI:10.1021/acscatal.6b01774

The use of ligands to tune the reactivity and selectivity of transition-metal catalysts for C(sp³)-H bond activation is a current central challenge. One of us previously developed an uncommon example of a homogeneous catalyst that performs controlled C(sp³)-H arylation using pyridine derivatives as ligands, along with Pd [Science, 2014, 343, 1216-1220]. In this work, we report a functionalizable and tunable polymer support used in the immobilization of pyridine derivatives that yields a soluble, polymeric ligand platform facilitating C(sp³)-H activation reactions with good yields, selectivities differing from the homogeneous catalyst, and recovery of Pd. Unlike the homogeneous system, the supported catalysts in Pd-catalyzed C-H monoarylation reactions respond sensitively to the steric hindrance of the coupling partners.

Full text of DOI:10.1021/acscatal.6b01774

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Letter
Functionalized Polymer-Supported Pyridine
Ligands for Palladium-Catalyzed C(sp3)–H Arylation
Li-Chen Lee, Jian He, Jin-Quan Yu, and Christopher W Jones
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b01774 • Publication Date (Web): 07 Jul 2016
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ACS Catalysis
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Functionalized Polymer-Supported Pyridine Ligands for
Palladium-Catalyzed C(sp3)–H Arylation
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Li-Chen Lee,a Jian He,b Jin-Quan Yu,b* Christopher W. Jonesa*
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aSchool of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0100, United States
bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037-1001, United States
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ABSTRACT: The use of ligands to tune the reactivity and selectivity of transition metal catalysts for C(sp3)–H bond
activation is a current central challenge. One of us previously developed an uncommon example of a homogeneous catalyst
that performs controlled C(sp3)–H arylation using pyridine derivatives as ligands along with Pd in Science 2014, 343, 1216-
1220. In this work, we report a functionalizable and tunable polymer support used in the immobilization of pyridine
derivatives that yields a soluble, polymeric ligand platform facilitating C(sp3)–H activation reactions with good yields,
selectivities differing from the homogeneous catalyst and recovery of Pd. Unlike the homogeneous system, the supported
catalysts in Pd-catalyzed C–H monoarylation reactions respond sensitively to the steric hindrance of the coupling partners.
KEYWORDS: C–H activation , arylation , polymerꢀsupported ligand, immobilized catalyst, palladium
The possibility of direct introduction of
a
new ligands tested, 2-methylpyridine provided the optimal
functionality (or a new C–C bond) via a direct C–H bond balance between yield and mono- versus di-arylation
transformation is a highly attractive strategy in organic selectivity in these homogeneous reactions.
synthesis. The range of substrates has been expanded to
However, examples exploring the use of heterogeneous
simple hydrocarbons, complex organic small molecules, and
catalysts in C–H functionalization reactions are
synthetic and biological polymers.1-7 Transition metal
catalysis has been used extensively in recent years to assist
in converting unactivated C–H bonds to more reactive
carbon–metal bonds that can subsequently be further
functionalized to afford the desired products.8-15
uncommon.28 In the Son and Shin groups,29 palladium
nanoparticles supported on silica nanotubes have been used
to catalyze C(sp2)–H arylation. Selective heterogeneous C–
H halogenation methods using palladium nanoparticles
immobilized into porous metal organic frameworks (MOFs)
In general, ‘inert’ C(sp3)–H bonds possess low reactivity have been reported.30,31 Impregnated Pd(OAc)2 on the MOF-
and high thermodynamic stability compared to the C(sp2)–H 5 (Oh) has been employed as a heterogenous Pd catalyst with
and C(sp)–H bonds.16 This makes C(sp3)–H activation a ultrahigh surface area. This supported catalyst was applied
more challenging endeavor compared to conventional C–H in the C–H phenylation of naphthalene.32 A Pd/C catalyzed
functionalization routes. A number of catalytic systems have arylation of triphenylene with aryiodonium salts has also
been recently developed for Pd-catalyzed C–H activation.17- been reported recently.33
22
In particular, directed Pd-catalyzed C(sp3)–H arylation
Herein, we report a functionalizable and tunable polymer
reactions have been developed recently. In 2005, the Pd-
used for the immobilization of pyridine ligands that yields a
soluble, polymeric ligand platform that facilitates C(sp3)–H
catalyzed, 8-methylquinoline- and 2-ethylpyridine-directed
C(sp3)–H arylation with aryl iodides was reported by the
activation reactions. When substituted for the homogeneous
Daugulis group.23 A Pd-catalyzed β–C(sp3)–H arylation of
pyridine ligands developed previously under Pd-catalyzed
C(sp3)–H activation conditions,1 the resulting catalyst not
carboxylic acids with aryl iodides was also achieved by the
Yu group subsequently.24
only offers comparable catalytic activity to the unsupported
Most compounds contain multiple types of C–H bonds and catalyst system, but it allows for catalyst recovery, new
other functional groups, and controlling site selectivity in C– catalytic selectivity not observed in the unsupported system,
H activation is necessary to help C–H functionalization and some catalyst recyclability. To the best of our
methods become widely useful. To this end, the use of knowledge, this represents the first C(sp3)–H activation of
ligands to tune the reactivity and selectivity of transition an amino acid derivative using a polymer-supported Pd
metal catalysts for C(sp3)–H bond activation has been a key catalyst.
recent focus. Recently, one of us reported the first example
This new polymer was constructed based on monomer 6,
which has two cross-linkable acrylamide and one benzyl
bromide functional group (Scheme 1). A low molecular
weight polymer backbone was formed by radical
of ligand-controlled C(sp3)–H arylation of an amino acid.1
Alanine-derived amide 1 bearing a weakly coordinating
aniline auxiliary17,25-27 in conjunction with Pd and various
pyridine and quinoline-based ligands were used. We found
polymerization between styrene and monomer 6 (Scheme
that pyridine-based ligands were capable of lowering the
1). Based on an investigation of the relative rates of
transition state energy of C(sp3)–H activation, and promoted
the selective monoarylation of a C(sp3)–H bond with aryl
iodides. Among the various pyridine-based
disappearance of monomer 6 and styrene by in situ 1H NMR
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Scheme 1. General preparation of the polymer-supported pyridine derivative used as a ligand for Pd-catalyzed C(sp3)–H
arylation.
(Figure S3), it is apparent that the polymerization
proceeded to form a mostly random copolymer. Figure S4
shows the integration ratios between styrene (He) and
monomer 6 (Hb) during polymerization, and it was
observed that the ratio increased modestly in the first four
hours and then remained constant during the rest of the
reaction. The amide functional groups within the polymer
backbone, based on alanine-derived amide 1, were
specifically included to help concentrate the polar
substrates within the polymeric domains, extracting these
species from the relatively non-polar reaction solutions,34 to
help accelerate the catalytic reactions. Once the polymeric
ligand backbone was prepared, a pyridine-based ligand was
post-modified35 onto the polymer by amination of the
benzyl bromide functional group within the polymer using
commercially available 4-amino-2-methylpyridine, L3
(Scheme 1). The completion of the ligand-modification was
similar chemical structures to the optimal ligands
previously identified by the Yu group,1 but were also
immobilizable via reaction with a benzyl bromide group
onto our polymeric support (Scheme 1). Ligands L1 and
L2 were highly selective for monoarylation, but neither
enhanced the conversion substantially relative to the
ligand-free catalyst. Ligand L3 enhanced the reactivity
relative to the ligand-free conditions, while offering good
selectivity to the monoarylation product. The N-alkylated
ligand, L4, also showed similar reactivity, suggesting that
incorporation of L3 into a polymer backbone (Scheme S1)
would not negatively affect catalytic reactivity from an
electronic perspective. Interestingly, the molecular ligands
L3 and L4, which had similar chemical structures to the
polymer-supported ligand PL(4), showed slightly lower
yields of monoarylated product than the polymer-supported
ligand. PL(4) seemed to possess a useful balance of steric
and electronic properties that provided compound 2 in high
yield and with excellent selectivity for monoarylation.
1
monitored by H NMR (Figure S6). As noted above, the
coordination environment of the supported ligand within
the polymer and metal was adjusted by tuning the ratios of
the functionalized monomer and styrene during polymer
preparation, altering the spacing between the ligands within
the polymer. In this work, the polymer-support is
abbreviated as “PL”, and the ratio of styrene to monomer is
added in parenthesis afterwards.
We hypothesize that the polar amide functional groups in
the polymer backbone helped to accelerate the reaction by
concentrating the substrate in the polymer domains,
partitioning from the relatively hydrophobic solution, while
maintaining high selectivity for monoarylation. An array of
polymer-supported ligands were thus prepared to have
ratios of styrene to functionalized monomer ranging from 2
to 8 and subsequently the impact of the polymer
composition on the performance in the target arylation
reaction was evaluated. Figure 1 shows that the polymer
supported ligand constructed with a styrene/monomer ratio
of 4 ratio yielded the highest reactivity and product
selectivity (PL(4)). Based on our observations, polymers
with a lower ratio of styrene to functionalized monomer
The Yu group previously developed reaction conditions
for the target reaction between alanine-derived amide 1 and
iodobenzene: 10 mol% Pd(TFA)2, 20 mol% ligand, 20
mol% TFA, Ag2CO3 (1.5 equiv.), iodobenzene (1.5 equiv.)
in 1,2-dichloroethane (DCE) at 100 oC to prepare
compound 2 in good yield and selectivity.1 Table 1 reports
data under identical reaction conditions from tests of a
library of homogeneous pyridine-based ligands that had
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Table 1. Yields obtained during ligand screening in the Pd-catalyzed C(sp3)–H monoarylation of alanine-derived amide 1
and iodobenzene.a, b
1
2
3
4
5
6
10 mol% Pd(TFA)2
20 mol% ligand
NPhth
CONHArF
NPhth
CONHArF
NPhth
CONHArF
+
H
TFA, Ph-I, Ag2CO3, DCE
100 oC, 20h
H
1
7
2
3
ArF = 4-(CF3)C6F4
8
9
O
O
Br
10
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N
N
CH2
N
H
H
m
m
n
NH2
NH2
NH2
NH2
NH2
Br
Me
Br
Me
No ligand
Me
N
Me
Me
N
N
N
MeO
N
PL(4)
L1
L2
L3
L4
2:
3:
44 %
1 %
61 %
2 %
46 %
2 %
61 %
1 %
21 %
0 %
70 %
3 %
a Substrate (0.1 mmol), Pd(TFA)2 (0.01 mmol), ligand (0.02 mmol), and Ag2CO3 (0.15 mmol) were weighed open to air and
placed in a pressure tube (5 mL) with a magnetic stir bar. The iodobenzene (0.15 mmol), TFA (0.02 mmol), and DCE (0.5
mL) were added. The reaction vessel was sealed and the mixture was first stirred at room temperature for 10 min and then
heated to 100 °C for 20 hours with vigorous stirring. b The yield % and ratios of products 2 to 3 were determined by H
1
NMR.
concentration of ligand (Table S3, styrene/monomer = 2
and 3, PL(2), PL(3)), did not as effectively facilitate the
PhthN
O
reaction either (Figure 1, styrene/monomer = 2 and 3,
PL(2), PL(3)). These ligands may have dramatically
lowered the energy of palladacycle intermediate via
chelation effect, thus impeding the subsequent
functionalization step of this C(sp3)–H arylation reaction.
We hypothesize that the best polymer provided an optimal
balance of solubility and correct spatial coordination with
the Pd species.
10 mol%
N
ArF
Me
NPhth
CONHArF
NPhth
CONHArF
Intermediate A
Pd
H
N
N
TFA, Ph-I
Ag2CO3, DCE
100 0C, 20h
H
Me
Intermediate A
1
2, 95%
ArF = 4-(CF3)C6F4
Scheme 2. Catalytic reactivity of intermediates in the
C(sp3)–H arylation reaction.
showed poor solubility in dichloroethane, hampering their
utility.
Previously, to gain insight into the coordination of the
substrate and ligand at the Pd(II) center, the Yu group
prepared and characterized a C–H insertion intermediate
formed via primary C(sp3)–H arylation in the absence of
aryl iodides.1 This intermediate was demonstrated to be a
viable precatalyst for primary C(sp3)–H arylation (Scheme
2). We hypothesized that some of the polymers prepared in
this work might not easily facilitate the formation of this
C–H insertion intermediate due to spatial constraints within
the polymer. For example, the polymers that had a lower
ligand density (Table S3, styrene/monomer = 8, PL(8))
might inhibit the proper coordination between two pyridine
ligands and Pd during the reaction, giving lower product
Figure 1. Yield of monoarylation product 2 from reactions
using polymers with various ratios of styrene to functional
yields (Figure 1, styrene/monomer
=
8, PL(8)).
Interestingly, the polymers that had relatively high
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b
monomers in the Pd-catalyzed C(sp3)–H monoarylation.
The experimental conditions were the same as in Table 1.
10 min and then heated to 100 °C for 20 hours with vigorous stirring.
The yield % and ratios of products 2 to 3 were determined by 1H NMR.
1
2
3
4
5
6
7
8
9
During the reaction, we hypothesize that the polar amide
substrate would be concentrated within the polymer due to
the relatively polar amide-based backbone when the
reactions were conducted in relatively non-polar solvents.
In such a scenario, the substrate and Pd-ligand complexes
would be in close proximity. This hypothesized preferential
interaction of the amide substrate with the functionalized
polymer backbone was supported by observed differences
in reactivity using various organic solvents (Table 2). The
reaction proceeded smoothly in nonpolar solvents (entries1
and 2, Table 2), whereas more polar solvents lowered the
reaction yield progressively (entries 5 and 6, Table 2). To
obtain the optimal balance of selectivity and yield, we used
a cyclohexane/DMF mixed solution as the reaction solvent
for further studies. In Figure 2, various volume ratios of
cyclohexane and DMF were studied in the monoarylation
reaction. When the cyclohexane/DMF volume ratio was 8,
both outstanding selectivity (94 %) and yield of the
monoarylation product (91 %) were obtained. In Yu’s
previous work, 2-methylpyridine was successfully used as
the ligand in conjunction with Pd to synthesize
phenylalanine derivatives (2a-2f) with electron-rich or
electron-poor groups at the orthoꢀ, metaꢀ, or para-positions
in high yields.1
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Figure 2. Pd-catalyzed C(sp3)–H monoarylation selectivity
and yield in cyclohexane/DMF mixed solutions. The
experimental conditions are the same as in Table 2.
reactive compared to the electron-donating substituted aryl
iodides. Interestingly, the polymer-supported ligand
showed steric selectivity of aryl iodide partners in
monoarylation reactions, which has not been observed in
the previous homogeneous Pd-ligand catalyzed reaction.1
With the supported catalyst, the yields were decreased
significantly when the substituents on the aromatic ring
were close to the active site (2a, 2b, and 2e, Table 3).
Apparently, Pd ligated to the immobilized ligand was
impacted by steric constraints associated with the polymer
support. For example, when methoxy substituted
iodobenzenes were used as the coupling partners in this
This reaction was also demonstrated to be tolerant of
halide substituents and a wide range of polar functional
groups. Herein, we evaluated the catalytic activity of PL(4)
with aryl iodides bearing both mono- and di-substituted
electron-donating or electron withdrawing groups under
our optimized reaction conditions. Overall, the electron
withdrawing substituted aryl iodides were less
Table 2. Solvent effect in Pd-catalyzed C(sp3)–H
C(sp3)–H
monoarylation,
ortho-methoxyiodobenzene
monoarylation of alanine-derived amide
1
and
showed significantly lower conversion than para-
methoxyiodobenzene (2a1 and 2a3, Table 3). This
phenomenon was also observed in ester and fluoro-
substituted iodobenzenes as well (2b1 and 2b3; 2e1 and 2e3,
Table 3), where iodobenzenes bearing substituents at the
meta-position showed more moderate conversions (2a2,
2b2 and 2e2, Table 3). This unique property could be
potentially exploited in protocols aimed at selective C(sp3)–
H monoarylation with aryl iodides that contain multiple
iodides.
iodobenzene.a, b
10 mol% Pd(TFA)2
NPhth
NPhth
CONHArF
NPhth
CONHArF
PL(4)
20 mol%
+
H
CONHArF
TFA, Ph-I
H
Ag2CO3, solvent
100 0C, 20h
1
2
3
ArF = 4-(CF3)C6F4
Entry
Solvent
Cyclohexane
DCE
Yield (%)b
2:3b
68:9
70:3
56:1
54:1
40:0
7:0
1
2
3
4
5
6
77
73
57
55
40
7
The supported ligand, when combined with Pd, yielded a
highly effective catalyst, providing altered selectivities and
improved yield of the monoarylated product compared to
the homogeneous catalyst under identical reaction
conditions, which is by itself a useful advance. Supported
catalysts offer the potential to also recover and recycle the
valuable and expensive Pd. To investigate the potential
recyclability of the polymer-supported ligand in Pd-
catalyzed C(sp3)–H monoarylation reactions, we used
PL(4) and iodobenzene as the model ligand and substrate
with DCE as the reaction solvent for ligand recovery and
recycle studies (Table 4). As expected, as a control, it was
noted that the C(sp3)–H monoarylation reaction failed in
Toluene
1,4-Dioxane
DMF
CH3CN
a Substrate (0.1 mmol), Pd(TFA)2 (0.01 mmol), PL(4) (0.02 mmol), and
Ag2CO3 (0.15 mmol) were weighed out open to air and placed in a
pressure tube (5 mL) with a magnetic stir bar. The iodobenzene (0.15
mmol), TFA (0.02 mmol), and solvent (0.5 mL) were added. The reaction
vessel was sealed and the mixture was first stirred at room temperature for
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Table 3. Substrate effects in the Pd-catalyzed C(sp3)–H
monoarylation using PL(4)
in a recycle test (Run 1* and 2, Table 4). Based on the
elemental analysis and H NMR of the reused material, we
1
1
2
3
4
5
6
7
8
verifed that we successfully recycled PL(4) and Pd with
high conversion (Table 4, Figure S7) after recovery from
the first reaction. This is thus an uncommon example of
ligand and metal recycling in a C(sp3)–H functionalization
reaction. Although the recovered PL(4) catalyst was not
robust after multiple runs (Run 3 and 3*, Table 4), the
recovery of the ligands and Pd metal is attractive and the
potential of developing more robust recyclable systems is
being explored.
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In conclusion, a functionalizable and tunable polymer
was synthesized and used in immobilization of pyridine
ligands for use in an important Pd-catalyzed C(sp3)–H
monoarylation reaction. Such C(sp3)–H activation reactions
have the potential to become useful tools to construct and
functionalize complex organic molecules. Notably, this is
the first example of polymer-supported catalyst that
selectively promotes C(sp3)–H monoarylation. The
immobilized ligand showed selectivity towards less
hindered aryl iodides, and was reusable with an identical
catalytic yield in a second cycle.
ASSOCIATED CONTENT
Supporting Information. Supporting Information Available:
[Experimental procedures, 1H, 13C NMR spectra and other
characterization data for the materials, reaction yields under
additional reaction conditions.] This material is available free of
charge via the Internet at http://pubs.acs.org.
Table 4. Recycling PL(4) in Pd-catalyzed C(sp3)–H
monoarylation a, b, c
AUTHOR INFORMATION
Corresponding Authors
cjones@chbe.gatech.edu
yu200@scripps.edu
Run
1
Ligand
Pd(TFA)2 Yield(%)b 2 : 3b
0
N.R.c
73
N.D.c
70:3
70:2
71:2
N.D.c
40:0
PL(4)
1*
2
10 mol%
0
ACKNOWLEDGMENTS
Recycled PL(4)
from run 1*
Recycled PL(4)
from run 2
72
2*
3
10 mol%
0
73
<5
We thank the NSF under the Center for Selective C–H
Functionalization (CCHF), No. CHE-1205646. Especially
thanks Dr. Gelbaum’s assistance for in situ 1H NMR
experiments for polymerization.
3*
10 mol%
40
a
Substrate (1.0 equiv.), Pd(TFA)2 (0.1 equiv.), PL(4) (0.2 equiv.), and
Ag2CO3 (1.5 equiv.) were weighed out open to air and placed in a pressure
tube (5 mL) with a magnetic stir bar. The iodobenzene (1.5 equiv.), TFA
(0.2 equiv.), and DCE were added. The reaction vessel was sealed and the
mixture was first stirred at room temperature for 10 min and then heated to
REFERENCES
(1)
He, J.; Li, S.; Deng, Y.; Fu, H.; Laforteza, B. N.; Spangler, J. E.;
Homs, A.; Yu, J. Q. Science 2014, 343, 1216-1220.
Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011,
40, 5068-5083.
(2)
b
100 °C for 20 hours with vigorous stirring. The yield % and ratios of
1
c
products 2 to 3 were determined by H NMR N.R. means no reaction;
(3)
(4)
Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651-3678.
Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev.
2011, 40, 4740-4761.
N.D. means not determined
(5)
Guo, X.-X.; Gu, D.-W.; Wu, Z.; Zhang, W. Chem. Rev. 2015, 115,
1622-1651.
the absence of Pd1 (Run 1, Table 4). Subsequently, the
reaction was run under standard conditions, using the
polymeric ligand PL(4) in conjunction with Pd.
Interestingly, the used PL(4) that was collected after the
first run reaction gave an identical yield of the coupled
product as the fresh PL(4) in the absence of additional Pd
(6)
(7)
Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147-1169.
Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. Chem. Rev. 2010, 110, 890-931.
Shang, R.; Ilies, L.; Asako, S.; Nakamura, E. J. Am. Chem. Soc.
2014, 136, 14349-14352.
(8)
(9)
Hwang, H.; Kim, J.; Jeong, J.; Chang, S. J. Am. Chem. Soc. 2014,
136, 10770-10776.
5
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(10) Yang, G.; Lindovska, P.; Zhu, D.; Kim, J.; Wang, P.; Tang, R.-Y.;
TABLE OF CONTENTS
Movassaghi, M.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 10807-
10813.
1
2
3
4
5
6
7
8
9
(11) Xiao, K.-J.; Lin, D. W.; Miura, M.; Zhu, R.-Y.; Gong, W.; Wasa,
M.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 8138-8142.
(12) Li, S.; Chen, G.; Feng, C.-G.; Gong, W.; Yu, J.-Q. J. Am. Chem.
Soc. 2014, 136, 5267-5270.
(13) Foo, K.; Sella, E.; Thomé, I.; Eastgate, M. D.; Baran, P. S. J. Am.
Chem. Soc. 2014, 136, 5279-5282.
(14) Kang, T.; Kim, Y.; Lee, D.; Wang, Z.; Chang, S. J. Am. Chem Soc.
2014, 136, 4141-4144.
(15) Kim, H. J.; Ajitha, M. J.; Lee, Y.; Ryu, J.; Kim, J.; Lee, Y.; Jung,
Y.; Chang, S. J Am Chem Soc 2014, 136, 1132-1140.
(16) Noisier, A. F.; Brimble, M. A. Chem. Rev. 2014, 114, 8775-8806.
(17) Chen, X.; Engle, K. M.; Wang, D. H.; Yu, J. Q. Angew. Chem. Int.
Ed. 2009, 48, 5094-5115.
(18) Guo, P.; Joo, J. M.; Rakshit, S.; Sames, D. J. Am. Chem. Soc. 2011,
133, 16338-16341.
(19) Affron, D. P.; Davis, O. A.; Bull, J. A. Org. Lett. 2014, 16, 4956-
4959.
(20) Cui, W.; Chen, S.; Wu, J.-Q.; Zhao, X.; Hu, W.; Wang, H. Org.
Lett. 2014, 16, 4288-4291.
(21) Campeau, L.-C.; Rousseaux, S.; Fagnou, K. J. Am. Chem. Soc.
2005, 127, 18020-18021.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(22)
Liu, J.; Xie, Y.; Zeng, W.; Lin, D.; Deng, Y.; Lu, X. J. Org.
Chem. 2015, 80, 4618-4626.
(23)
(24)
Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7, 3657-3659.
Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510-
3511.
(25)
(26)
Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res.
2012, 45, 788-802.
He, J.; Jiang, H.; Takise, R.; Zhu, R.-Y.; Chen, G.; Dai, H.-X.;
Dhar, T. G. M.; Shi, J.; Zhang, H.; Cheng, P. T. W.; Yu, J.-Q.
Angew. Chem. In.Ed. 2016, 55, 785-789.
(27)
He, J.; Takise, R.; Fu, H.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137,
4618-4621.
(28)
(29)
Pla, D.; Gómez, M. ACS Catal. 2016, 3537-3552.
Park, G.; Lee, S.; Son, S. J.; Shin, S. Green Chem. 2013, 15,
3468.
(30)
(31)
Fei, H.; Cohen, S. M. J. Am. Chem. Soc. 2015, 137, 2191-2194.
Pascanu, V.; Carson, F.; Solano, M. V.; Su, J.; Zou, X.;
Johansson, M. J.; Martin-Matute, B. Chem. Eur. J. 2016, 22,
3729-3737.
(32)
(33)
Park, T.-H.; Hickman, A. J.; Koh, K.; Martin, S.; Wong-Foy, A.
G.; Sanford, M. S.; Matzger, A. J. J. Am. Chem. Soc. 2011, 133,
20138-20141.
Collins, K. D.; Honeker, R.; Vasquez-Cespedes, S.; Tang, D.-T.
D.; Glorius, F. Chem. Sci. 2015, 6, 1816-1824.
Lee, L.-C.; Zhao, Y. J. Am. Chem. Soc. 2014, 136, 5579-5582.
Datta, A.; Plenio, H. Chem. Commun. 2003, 1504-1505.
(34)
(35)
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