Cobalt(III)-catalyzed alkenylation of arenes and 6-arylpurines with terminal alkynes: Efficient access to functional dyes

Article abstract of DOI:10.1039/c5cc09707j

Alkenylation of unactivated arenes and 6-arylpurines with terminal alkynes in high yields using Cp?Co(CO)I₂ as catalyst under mild conditions is described. This method shows outstanding functional group compatibility and can be applied in the d

Full text of DOI:10.1039/c5cc09707j

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Cobalt(III)-Catalyzed Alkenylation of Arenes and
6-Arylpurines with Terminal Alkynes: Efficient Access to
Functional Dyes
Shan Wang, Ji-Ting Hou, Mei-Lin Feng, Xiao-Zhuan Zhang, Shan-Yong Chen,*
Xiao-Qi Yu*
A method for cobalt(Ⅲ)-catalyzed alkenylation of arenes and 6-arylpurines has been developed.
This reaction undergoes under mild conditions with only equivalent terminal akynes in high yields.
A mitochondria-targeted imaging dye was simply prepared through this method, which signifies
this cobalt-catalyzed alkenylation can provide efficient access to design of functional dyes.

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DOI: 10.1039/C5CC09707J
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ARTICLE TYPE
Cobalt(III)-Catalyzed Alkenylation of Arenes and 6-Arylpurines with
Terminal Alkynes: Efficient Access to Functional Dyes
Shan Wang, Ji-Ting Hou, Mei-Lin Feng, Xiao-Zhuan Zhang, Shan-Yong Chen,* Xiao-Qi Yu*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
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DOI: 10.1039/b000000x
acidic terminal protons and easily selfꢀdiꢀ or trimerize in
transitionꢀmetal catalysis, so they are usually considered
50 nontrivial substrates in CꢀH alkenylation reactions.13,10a,11a
Actually, carbonꢀcarbon double bond can act as a very important
linker in many functional dyes, with broad uses in fine chemistry
and biological imaging.14 However, the previously reported
alkenylation methods have rarely been applied in the construction
55 of dyes. Here we report the Cp*Co(Ⅲ)ꢀcatalyzed direct addition
of unactivated arenes and 6ꢀarylpurines to terminal alkynes. In
particular, only one equivalent terminal alkynes are needed here,
indicating the high performance of this reaction. To confirm the
potential, a mitochondriaꢀtargeted imaging dye was simply
60 prepared through this method, which shows that this cobaltꢀ
catalyzed alkenylation can provide efficient access to the design
of functional dyes.
An alkenylation of unactivated arenes and 6-arylpurines with
terminal alkynes in high yields using Cp*Co(CO)I2 as
catalysts under mild conditions is described. This method
shows outstanding functional group compatibility and can be
10 applied into the design of a mitochondria-targeted imaging
dye.
The direct functionalization of carbon–hydrogen (CꢀH) bonds
provides an atomꢀeconomical and environmentally friendly
synthetic method as it avoids the prefunctionalization of coupling
15 partners.1 The transitionꢀmetalꢀcatalyzed alkenylation of
unreactive aryl CꢀH bonds with alkynes is among the most
significant transformations in organic synthesis2 because of the
abundance of starting materials, the 100% atomꢀeconomy and the
oxidantꢀfree reaction conditions. It can be applied to extending πꢀ
20 systems to construct functional dyes. While most achievements in
alkenylation via alkynes have been accomplished with noble
metal catalyst systems, such as ruthenium,3 rhodium,4 palladium,5
and rhenium,6 earthꢀabundant and inexpensive firstꢀrow transition
metals with potentially novel reactivity have drawn special
25 attention to CꢀH activation reactions.7 In this connection, the
lowꢀvalent cobaltꢀcatalyzed CꢀH transformations pioneered by
Nakamura, Yoshikai and Ackermann have recently been achieved
Scheme 1. The optimized reaction conditions
After extensive screening, we were delighted to find that 2ꢀ
65 phenylpridine (1a) underwent
direct alkenylation with
9
under mild conditions,8, and the lowꢀvalent cobaltꢀcatalyzed
phenylacetylene (2a) under a Cp*Coꢀcatalyzed system. In a
typical experiment, the treatment of 1a with 2a in the presence of
5 mol% Cp*Co(CO)I2, 10 mol% AgSbF6 and 0.5 equiv PivOH in
DCE at 60 °C afforded the corresponding product 3a in 86%
70 yield (Scheme 1). Using the optimized reaction conditions, the
scope of substituted 2ꢀphenylpyridines and heteroarenes was
investigated (Table 1). Substituents on benzene rings with
disparate electronic properties have no obvious bias on the
formation of products. Remarkably, substrates containing halogen
75 groups were also wellꢀsuited to the standard reaction conditions
with great yields (3c, 3e and 3g) and allow additional
modification. Additionally, substituents at the meta, or para
positions did not obviously affect the efficiency of this
transformation (3bꢀ3e). When two adjacent CꢀH bonds existed in
80 the metaꢀsubstituted benzene moiety, single regioisomers of less
steric bulkiness were obtained in high yields (3dꢀ3e), suggesting
perfect regioselectivity. Furthermore, when substituted pyridine
rings were used, regardless of the electronic nature of the
substituent, the addition proceeded well (3fꢀ3g). Meanwhile,
85 derivatives with other Nꢀheterocycles as directing groups were
[journal], [year], [vol], 00–00 | 1
alkenylation of aryl CꢀH has been developed by Yoshikai.9e, 9f
30 However, Grignard reagents were necessary in lowꢀvalent Co
catalyst systems, which introduced some undesirable coupling
reactions or dehydrohalogenation of the electrophiles. Lately,
highꢀvalent cobalt(III) catalysts have been employed for
chemoselective and regioselective CꢀH functionalization10, 11 and
35 these Cp*Co(III)ꢀcatalyzed systems can avoid consuming
Grignard reagents. Recently, Matsunaga & Kanai reported a
seminal work on Cp*Co(III)ꢀ catalyzed C2ꢀalkenylation of
indoles10a. Considering the reactivity of indole CꢀH is higher than
that of benzene CꢀH, Cp*Co catalyzed alkenylation of generally
40 unreactive aryl CꢀH has not yet been reported. Additionally,
alkenylations reported before usually need harsh conditions like
high temperature, which go against the introduction of sensitive
groups. Therefore, alkenylation of generally unactivated aryl CꢀH
under mild conditions is still in urgent demand.
45
Compared with internal alkynes, terminal alkynes are rarely
used as alkenylation reactants in chelationꢀassisted aromatic CꢀH
bond reactions.12 Remarkably, terminal alkynes contain relatively
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also examined. Pyrazole (1h) worked well only giving monoꢀ
phenylacetylenes substituted with strongly electronꢀwithdrawing
additive product, while pyrimidine (1i) and 2ꢀphenylthiazole (1j) 25 groups could attain acceptable yields with the temperature
achieved both monoꢀadditive products and doubleꢀadditive
products. These phenomena might be due to the different
numbers of coordinated atoms on the directing moiety. When the
equivalent of 2a was improved, the yields of the alkenylated
increased to 100 °C (4f, 4g). Metaꢀsubstituents on the benzene
moiety displayed no apparent effect on the outcome (4h),
although orthoꢀsubstituted groups entirely restrained the reaction.
It is noteworthy that sensitive functional groups, –Br and ꢀCHO
5
products of 1i and 1j increased, and the amounts of doubleꢀ 30 in particular, remained intact after reaction, providing easy
additive products were elevated. Moreover, heteroarenes were
compatible with the reaction conditions. Both thiophene and
10 indole heterocyclic substrates remained reactive under these
handles for further synthetic embellishments (4d, 4e, 4g). As an
example of a heteroaromatic alkyne, 3ꢀethynylthiophene is also
efficiently amenable to this method (4i). In addition, aliphatic
alkyne is compatible with the reaction conditions, affording diꢀ
conditions (3k, 3l). The addition of 2ꢀthiophenylpyridine
occurred at the 3ꢀposition of thiophene in 99% yield although the 35 substituted alkene (4j) in 93% yield.
CꢀH bond adjacent to the Sꢀatom is often susceptible (3k). The
alkenylation of indoles with terminal alkynes reported by
Table 2. Scope of substituted phenylacetylene.a,b
15 Matsunaga & Kanai required 130 °C and long reaction time (20
h).10a Under our conditions, 1ꢀ(pyrimidinꢀ2ꢀyl)ꢀ1Hꢀindole (1l)
was almost entirely alkenylated at room temperature in ten
minutes due to the higher reactivity of Cꢀ2 heteroaryl CꢀH.
Table 1. Substrate scope of addition of (hetero)arene CꢀH Bonds.a,b
4a, 94%
4b, 78%
4c, 91%
4d, 93%
4h, 83%
a) Arenes
4e, 92%
4i, 90%
4f, 69%c
4j, 93%
4g, 74%c
3a, 86%
3e, 86%
3b, 80%
3f, 83%
3c, 87%
3d, 85%
3h, 75%
a
1a (0.2 mmol), 2 (0.2 mmol), Cp*Co(CO)I2 (5 mol%), AgSbF6 (10
mol%), PivOH (0.5 equiv), DCE (1 mL), 60 oC, 5 h. Isolated yields.
b
c 100 oC.
3g, 86%
6ꢀArylpurines have been identified with a variety of valuable
biological properties, such as antiꢀmycobacterial, cytostatic, and
antiꢀHCV activities.15 Consequently, selectively constructing
40 functional 6ꢀarylpurines is significant for emergency. However,
and
3i and 3i’, 69%
(3i, 40% and 3i’, 28%)c
3i and 3i’, 83%
N
N
Ph
Ph
(3i, 28% and 3i’, 58%)d
3j and 3j’, 60%
and
even the noble metalꢀcatalyzed direct CꢀH functionalization of 6ꢀ
(3j, 25% and 3j’, 37%)c,e
3j and 3j’, 80%
arylpurines is rare,16 let alone the firstꢀrow metal.10h,
6ꢀ
10i
Arylpurine is possible to form a thermodynamically stable fiveꢀ
membered metalloꢀcycle just like 2ꢀphenylpyridine. Therefore,
45 we were interested in whether the addition of terminal alkynes
could also be performed with the purine moiety.
(3j, 16% and 3j’, 66%)d,e
b) Heteroarenes
N
N
Delightly, the direct addition of 6ꢀarylpurines to terminal
alkynes proceeded very smoothly under the standard conditions
(Table 3). 6ꢀArylpurines with different N9ꢀsubstituents did not
50 demonstrate any obvious bias on reactivity. N9ꢀisopropylꢀ,
phenylꢀ, and benzylꢀ substituted 6ꢀarylpurines all served as
suitable substrates for the alkenylation, obtaining the desired
products in excellent yields (6aꢀ6c). Thereafter, the N9ꢀbenzyl
group could be removed straightforwardly. Whether the electronꢀ
55 donating methoxy group (6d) or the electronꢀwithdrawing chloro
group (6e) was located on the aryl side, outstanding yields could
be obtained. An analogous moiety without the N7ꢀnitrogen atom
was also tested (5f), and only the monoꢀadditive product was
N
3k, 99%
3l, 96%f
a
1 (0.2 mmol), 2a (0.2 mmol), Cp*Co(CO)I2 (5 mol%), AgSbF6 (10
mol%), PivOH (0.5 equiv), DCE (1 mL), 60 C, 5 h. Isolated yields. c
o
b
Yield based on 1. 2a (0.4 mmol). 100 oC. Without PivOH, room
d
e
f
temperature, 10 min. DCE = 1,2ꢀdichioroethane, Cp* = C5Me5.
20
Subsequently, different terminal alkynes were explored using
2ꢀphenylpyridine 1a as the substrate (Table 2). In optimized
conditions, phenylacetylenes bearing electronꢀdonating or weakly
electronꢀwithdrawing groups proceeded well (4aꢀ4e, 4h), while
2
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achieved in desirable yields. This result indicated that the N1ꢀ
nitrogen was the directing atom instead of the N7ꢀnitrogen16d and
with a high yield of 95%.
With the compound in hand, we first examined its optical
confirmed the fiveꢀmembered metalloꢀcycle mechanism we had 30 properties in different solvents. As shown in Table S1, the
envisioned before.
maximum absorption of InD ranged from 337 nm to 356 nm as
the solvent changed, while the emission showed a larger solvent
effect (from 459 nm in toluene to 558 in PBS). Encouragingly,
favourable large Stokes Shifts (121 ~ 210 nm) and high quantum
35 yields (as high as 0.95) of InD can be observed, which are of
potent significance in the design of cellular imaging agents, as
large Stokes Shifts can minimize selfꢀquenching and high
quantum yield will increase the imaging sensitivity.18, 19
Table 3. Direct CꢀH alkenylation of 6ꢀarylpurine derivatives.a,b
6a, 93%
6d, 93%
6b, 92%
6e, 92%
6c, 90%
6f, 94%
40 Figure 1. HepG2 cells were stained with InD (10 ꢁM) for 30 min, and
then incubated with MTG (1 ꢁM) for another 10 min. (a): fluorescence
image of MTG; (b): fluorescence image of InD; (c): merged images of (a)
and (b). Ex@488 nm for MTG (495ꢀ530 nm) and Ex@405 nm for InD
(530ꢀ610 nm).
a
1 (0.2 mmol), 2a (0.2 mmol), Cp*Co(CO)I2 (5 mol%), AgSbF6 (10
mol%), PivOH (0.5 equiv), DCE (1 mL), 60 oC, 5 h. b Isolated yields.
45
Subsequently, we set out to explore the intracellular imaging
ability of InD. First, a standard MTT assay showed acceptable
cytotoxicity of InD (Figure S2). Next, HepG2 cells were
incubated with 10 ꢁM InD for 30 min at 37 °C in PBS and
imaged by confocal laser scanning microscopy. Fluorescence
5
To our delight, there was no significant loss of yield when the
reaction of 1a and 2a was scaled up at least tenfold (Scheme 2).
A plausible reaction mechanism is described in supporting
information (Scheme S1).
50 could be clearly visualized in the cytoplasm of InDꢀloaded cells
(Figure S3), indicating the outstanding cellular penetrability of
InD. To further inspect the subcellular localization of InD, InD
was coꢀincubated with a commercially available mitochondrial
dye, Mito Tracker Green (MTG). As shown in Figure 1, the
55 fluorescence of InD overlaid very well with the fluorescence of
MTG, with Pearson's coꢀlocalization coefficient between InD and
MTG calculated to be 0.88, implying that InD was siteꢀ
specifically internalized in mitochondria in living cells. Thus, an
efficient mitochondriaꢀtargeted bioimaging agent based on an
60 indole skeleton was successfully prepared via cobaltꢀcatalyzed Cꢀ
H activation, suggesting that the alkenylation developed in our
work could be applied to the design of promising fluorescent
dyes.
Scheme 2. Preparative scale experiment.
10
The above findings that our method can amplify the
conjugation of aromatic rings by introducing a phenylethylene
moiety rendered us as to speculate whether this cobalt( Ⅲ)ꢀ
catalyzed alkenylation can be utilized to design novel fluorescent
dyes. Although widely found in natural products, indole is
15 essentially nonꢀfluorescent and is certainly uncommon in the
design of dyes. As 1ꢀ(pyrimidinꢀ2ꢀyl)ꢀ1Hꢀindole can be styrylated
easily under our conditions, we would like to develop a simple
preparation of fluorescent dyes based on an indole backbone by
cobalt(Ⅲ)ꢀcatalyzed addition.
Conclusions
65 In summary, we have reported an inexpensive Cp*Co (Ⅲ)ꢀ
catalyzed direct addition of unactivated arenes and 6ꢀarylpurines
to terminal alkynes under mild conditions. The process
selectively gives only (E)ꢀstereoisomers and demonstrates
excellent functional group compatibility with high yields. In this
70 reaction, only equivalent terminal alkynes are needed, indicating
the high performance of this reaction without the dimerization or
trimerization of alkynes. Furthermore, the direct addition of 6ꢀ
arylpurines to terminal alkynes was also realized via this method,
which may benefit the development of 6ꢀarylpurineꢀbased
N
N
CHO
N
OHC
20
Scheme 3. The structure of InD.
As the electronꢀwithdrawing formyl group is tolerated under
the mild conditions and the nitrogen atom in indole can act as an
electronꢀdonating moiety, formyl substituted indole and
25 phenylacetylene were chosen to construct the fluorescent dye InD
via the “DonorꢀTwoꢀAcceptor” strategy (Scheme 3), which can
promote a longer emission.17 InD was prepared in ten minutes
75 pharmaceutical chemistry. Finally,
a mitochondriaꢀtargeted
imaging dye was simply and effectively prepared through this
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Ed. 2011, 50, 1109; (c) Z. Ding and N. Yoshikai, Angew. Chem., Int.
Ed. 2012, 51, 4698; (d) J. V. Obligacion and S. P. Semproni, P. J.
Chirik, J. Am. Chem. Soc. 2014, 136, 4133.
mild method, which shows that this cobaltꢀcatalyzed alkenylation
can provide feasible access to the design of functional dyes.
Further investigation of the mechanism and application is in
progress in our laboratory.
70 9. (a) Q. Chen, L. Ilies and E. Nakamura, J. Am. Chem. Soc. 2011, 133,
428; (b) W. Liu, H. Cao, J. Xin, L.Jin and A. Lei, Chem. Eur. J.
2011, 17, 3588; (c) W. Song and L. Ackermann, Angew. Chem. Int.
Ed. 2012, 51, 8251; (d) K. Gao, P.ꢀS. Lee, C. Long, N. Yoshikai,
Org. Lett. 2012, 14, 4234; (e) K. Gao, P.ꢀS. Lee, T. Fujita, N.
5
Acknowledgment
75
Yoshikai, J. Am. Chem. Soc. 2010, 132, 12249; (f) P.ꢀS. Lee, T.
Fujita and N. Yoshikai, J. Am. Chem. Soc. 2011, 133, 17283.
10. For selective Cp*Co(III)ꢀcatalyzed direct C–H functionalizations,
see: (a) H. Ikemoto, T. Yoshino, K. Sakata, S. Matsunaga and M.
Kanai, J. Am. Chem. Soc. 2014, 136, 5424; (b) B. Sun, T. Yoshino, S.
Matsunaga and M. Kanai, Chem. Commun. 2015, 51, 4659; (c) J. Li
and L. Ackermann, Angew. Chem., Int. Ed. 2015, 54, 8551; (d) J. Li
and L. Ackermann, Angew. Chem., Int. Ed. 2015, 54, 3635 ; (e) D. G.
Yu, T. Gensch, F. d. Azambuja, S. V. Céspedes and F. Glorius, J.
Am. Chem. Soc. 2014, 136, 17722; (f) T. Gensch, S. V. Céspedes,
D.ꢀG. Yu and F. Glorius, Org. Lett. 2015, 17, 3714; (g) J. R.
Hummel and J. A. Ellman, J. Am. Chem. Soc. 2015, 137, 490; (h) P.
Patel and S. Chang, ACS Catal. 2015, 5, 853. (i) A. B. Pawar and S.
Chang, Org. Lett. 2015, 17, 660; (j) Z.ꢀZ. Zhang, B. Liu, C.ꢀY. Wang
and B.ꢀF. Shi, Org. Lett. 2015, 17, 4094; (k) E. Ozkal, B. Cacherat
and B. Morandi, ACS Catal. 2015, 5, 6458; (l) Y. Liang, Y.ꢀ F.
Liang, C. Tang, Y. Yuan and N. Jiao, Chem. Eur. J. 2015, 21, 16395;
(m) M. Sen, D. Kalsi and B. Sundararaju, Chem. Eur. J. 2015, 21,
15529.
This work was supported financially by the National Program on
Key Basic Research Project of China (973 Program,
10 2013CB328900) and the National Science Foundation of China
(Grant No. 21202107, 21321061 and J1103315).
80
Notes and references
Key Laboratory of Green Chemistry and Technology, Ministry of
Education, College of Chemistry, Sichuan University, Chengdu, 610064,
15 P. R. China. Tel. & Fax: (86)-28-85415886
85
E-mail: chensy@scu.edu.cn, xqyu@scu.edu.cn
† Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
20 ‡ Footnotes should appear here. These might include comments relevant
to but not central to the matter under discussion, limited experimental and
spectral data, and crystallographic data.
90
11. See also: (a) L. Grigorjeva and O. Daugulis, Angew. Chem., Int. Ed.
2014, 53, 10209; (b) L. Grigorjeva and O. Daugulis, Org. Lett. 2014,
16, 4684; (c) L.ꢀB. Zhang, X.ꢀQ. Hao, S.ꢀK. Zhang, Z.ꢀJ. Liu, X.ꢀX.
Zheng, J.ꢀF. Gong, J.ꢀL. Niu and M.ꢀP. Song, Angew. Chem., Int. Ed.
2015, 54, 272 and references therein.
12. (a) K. Cheng, B. Yao, J. Zhao and Y. Zhang, Org. Lett. 2008, 10,
5309; (b) M.ꢀH. Xie, M. Wang and C.ꢀD. Wu, Inorg. Chem. 2009,
48, 10477; (c) K. Gao, P.ꢀS. Lee, T. Fujita and N. Yoshikai, J. Am.
Chem. Soc. 2010, 132, 12249; (d) B. Zhou, H. Chen, C. Wang, J. Am.
Chem. Soc. 2013, 135, 1264; (e) F. Xie, Z. Qi, S. Yu and X. Li, J.
Am. Chem. Soc. 2014, 136, 4780.
1. For select recent reviews on transitionꢀmetalꢀcatalyzed CꢀH
95
25
functionalization: (a) L. Ackermann, Chem. Rev. 2011, 111, 1315; (b)
S. H. Cho, J. Y. Kim, J. Kwak and S. Chang, Chem. Soc. Rev. 2011,
40, 5068; (c) K. M. Engle, T.ꢀS. Mei, M. Wasa and J.ꢀQ. Yu, Acc.
Chem. Res. 2012, 45, 788; (d) B.ꢀJ. Li and Z.ꢀJ. Shi, Chem. Soc. Rev.
2012, 41, 5588.
100
30 2. For representative examples:(a) K. Ueura, T. Satoh and M. Miura,
Org. Lett. 2007, 9, 1407; (b) K. S. Kanyiva, N. Kashihara, Y. Nakao,
T. Hiyama, M. Ohashib and S. Ogoshi, Dalton Trans., 2010, 39,
10483; (c) X. G. Li, K. Liu, G. Zou, P. N. Liu, Eur. J. Org. Chem.
2014, 7878.
35 3. For selected recent examples, see: (a) L. Ackermann, A. V. Lygin and
N. Hofmann, Angew. Chem., Int. Ed. 2011, 50, 6379; (b) Y.
Hashimoto, K. Hirano, T. Satoh, F. Kakiuchi and M. Miura, Org.
Lett. 2012, 14, 2058; (c) M. Itoh, Y. Hashimoto, K. Hirano, T. Satoh
and M. Miura, J. Org. Chem. 2013, 78, 8098.
40 4. (a) D. A. Colby, R. G. Bergman and J. A. Ellman, J. Am. Chem. Soc.
2008, 130, 3645; (b) T. Katagiri, T. Mukai, T. Satoh, K. Hirano and
M. Miura, Chem. Lett. 2009, 38, 118; (c) Y. Shibata, Y. Otake, M.
Hirano and K. Tanaka, Org. Lett. 2009, 11, 689; (d) F. W. Patureau,
T. Besset, N. Kuhl and F. Glorius, J. Am. Chem. Soc. 2011, 133,
105 13. For dimerizations, see: (a) B. M. Trost, F. D. Toste and A. B.
Pinkerton, Chem. Rev. 2001, 101, 2067; (b) C. Jahier, O. V.
Zatolochnaya, N. V. Zvyagintsev, V. P. Ananikov and V. Gevorgyan,
Org. Lett. 2012, 14, 2846 and references therein. For trimerizations,
see: (c) G. Domínguez and J. PérezꢀCastells, Chem. Soc. Rev. 2011,
110
115
120
125
40, 3430.
14. J.ꢀT. Hou, J. Yang, K. Li, Y.ꢀX. Liao, K.ꢀK. Yu, Y.ꢀM. Xie and X.ꢀQ.
Yu, Chem. Commun. 2014, 50, 9947.
15. (a) L.ꢀL. Gundersen, J. NissenꢀMeyer and B. Spilsberg, J. Med.
Chem. 2002, 45, 1383; (b) M. Hocek, P. Nauš, R. Pohl, I. Votruba, P.
A. Furman, P. M. Tharnish and M. J. Otto, J. Med. Chem. 2005, 48,
5869 – 5873. (c) A. K. Bakkestuen, L.ꢀL. Gundersen and B. T.
Utenova, J. Med. Chem. 2005, 48, 2710.
16. (a) M. K. Lakshman, A. C. Deb, R. R. Chamala, P. Pradhan and R.
Pratap, Angew. Chem., Int. Ed. 2011, 50, 11400; (b) H.ꢀM. Guo, L.ꢀ
L. Jiang, H.ꢀY. Niu, W.ꢀH. Rao, L. Liang, R.ꢀZ. Mao, D.ꢀY. Li and
G.ꢀR. Qu, Org. Lett. 2011, 13, 2008; (c) H.ꢀM. Guo, W.ꢀH. Rao, H.ꢀ
Y. Niu, L.ꢀL. Jiang, G. Meng, J.ꢀJ. Jin, X.ꢀN. Yang and G.ꢀR. Qu,
Chem. Commun. 2011, 47, 5608; (d) H. J. Kim, M. J. Ajitha, Y. Lee,
J. Ryu, J. Kim, Y. Lee, Y. Jung and S. Chang, J. Am. Chem. Soc.
2014, 136, 1132.
45
2154.
5. (a) N. Tsukada, T. Mitsuboshi, H. Setoguchi and Y. Inoue, J. Am.
Chem. Soc. 2003, 125, 12102; (b) M. Ahlquist, G. Fabrizi, S. Cacchi
and P.ꢀO. Norrby, J. Am. Chem. Soc. 2006, 128, 12785; (c) N.
Chernyak and V. Gevorgyan, J. Am. Chem. Soc. 2008, 130, 5636.
50 6. (a) Y. Kuninobu, A. Kawata and K. Takai, J. Am. Chem. Soc. 2005,
127, 13498; (b) Y. Kuninobu, Y. Tokunaga, A. Kawata and K. Takai,
J. Am. Chem. Soc. 2006, 128, 202.
7. Selected reviews: (a) G. Rouquet and N. Chatani, Angew. Chem., Int.
Ed. 2013, 52, 11726; (b) T. K. Hyster, Catal. Lett. 2015, 145, 458; (c)
55
60
65
Y. Liang, Y.ꢀF. Liang and N. Jiao, Org. Chem. Front. 2015, 2, 403.
Manganese: (d) C. Wang, Synlett 2013, 24, 1606. Iron: (e) E.
Nakamura and N. Yoshikai, J. Org. Chem. 2010, 75, 6061; (f) I.
Bauer and H.ꢀJ. Knölker, Chem. Rev. 2015, 115, 3170. Cobalt: (g) K.
Gao and N. Yoshikai, Acc. Chem. Res. 2014, 47, 1208 ꢀ 1219. (h) L.
Ackermann, J. Org. Chem. 2014, 79, 8948. Nickel: (i) S. Z. Tasker,
E. A. Standley and T. F. Jamison, Nature 2014, 509, 299. ( j) X.ꢀH.
Cai and B. Xie, ARKIVOC 2015, 184. Copper: (k) R. T. Gephart, T.
H. Warren, Organometallics 2012, 31, 7728.
17. N. KartonꢀLifshin, L. Albertazzi, M. Bendikov, P. S. Baran and D.
Shaba, J. Am. Chem. Soc. 2012, 134, 20412.
18. W. Lin, L. Yuan, Z. Cao, Y. Feng, J. Song, Angew. Chem., Int. Ed.
2010, 49, 375.
130 19. X. Wu, S. Chang, X. Sun, Z. Guo, Y. Li, J. Tang, Y. Shen, J. Shi, H.
Tian, W. Zhu, Chem. Sci. 2013, 4, 1221.
8. For representative examples, see: (a) L. Ilies, Q. Chen, X. Zeng and E.
Nakamura, J. Am. Chem. Soc. 2011, 133, 5221; (b) B. Li, Z.ꢀH. Wu,
Y.ꢀF. Gu, C.ꢀL. Sun, B.ꢀQ. Wang and Z.ꢀJ. Shi, Angew. Chem., Int.
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