A sustainable and simple catalytic system for direct alkynylation of C(sp2)-H bonds with low nickel loadings

Article abstract of DOI:10.1039/c5cc01163a

A sustainable and simple catalytic system for the atom-economical alkynylation of benzamides with low nickel loadings is described. No organic or metallic oxidants and expensive ligands are required. A broad range of benzamides and bromoalkynes bearing various synthetically useful functional groups are compatible with this reaction. The versatility of this operationally simple protocol has been further demonstrated by the controllable mono- and di-alkynylation. Importantly, substrate/catalyst ratios of up to 200, and a turnover number of 196 were achieved, highlighting the potential of this protocol for synthetic applications.

Full text of DOI:10.1039/c5cc01163a

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A Sustainable and Simple Catalytic System for Direct Alkynylation of
C(sp2)–H Bond with Low Nickel Loadings
Yue-Jin Liu,a Yan-Hua Liu,a Sheng-Yi Yan,a Bing-Feng Shi*a,b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
A sustainable and simple catalytic system for the atom-economical alkynylation of benzamides with low
nickel loadings is described. No organic or metallic oxidants and expensive ligands are required. A broad
range of benzamides and bromoalkynes bearing various synthetically useful functional groups are
compatible with this reaction. The versatility of this operationally simple protocol has been further
10 demonstrated by the controllable mono- and di-alkynylation. Importantly, substrate/catalyst ratios of up to
200, and a turnover number of 196 were achieved, highlighting the potential of this protocol for synthetic
applications.
The discovery of novel transformations that are cost-effective
More recently, the Yu and Dai group12 and our group13 have
and sustainable to the construction of complex organic molecules 50 independently developed copper-mediated alkynylation of arenes
15 is the long-standing goal of synthetic chemists in both academia
and industry. Therefore, transition-metal-catalyzed direct
functionalization of C-H bonds represents one of the most
promising transformations.1 This strategy obviates the need to
with terminal alkynes. A broad range of terminal alkynes have
been used by Yu and Dai, however, only moderate yields have
been achieved and a stoichiometric amount of copper salt was
used as catalyst. Therefore, more sustainable catalytic system,
prefunctionalize the starting materials and reduces the production 55 employing significantly low loading of cheap metal catalyst, for
20 of undesired wastes, thus rendering synthetic routes more step-
and atom-economical. Despite these advantages, the inherent
limitations and challenges of C-H functionalization reactions
compared to traditional cross-coupling reactions cannot be
overlooked, such as the use of high catalyst loadings and
25 complicated catalytic systems with excess of additives or metallic
oxidants.1,2 Accordingly, the development of more effective and
simple catalytic systems for the direct functionalization of C-H
bonds at low catalyst loadings would be a considerable advantage
for industrial applications and for sustainable consideration.
the coupling of a wide array of diversely substituted arenes with
bromoalkynes are highly desirable.
30
The prevalence of alkynes in natural products, medicinal
targets, and functional materials has motivated tremendous efforts
directed toward the synthesis of these fundamental building
blocks.3 Recently, the emerged “inverse Sonogashira coupling”
involving the direct alkynylation of unactivated aryl C-H bonds
35 with alkynyl halides or pseudohalides has attracted much
attention.4,5 Palladium- and ruthenium-catalyzed alkynylation of
unactivated C-H bonds with (triisopropylsilyl)ethynyl bromide
(2a) was achieved by the Chatani and Yu groups with the
assistance of different kind of auxiliaries.6 Chang reported a Pd-
40 catalyzed alkynylation of N-aryl-2-aminopyridine with
(triisopropylsilyl)acetylene.7 In 2014, Loh,8 Li9a and Glorius9b
have reported Rh-catalyzed alkynylation of C(sp2)-H bonds with
hypervalent alkynyl iodine reagents. However, these methods
rely on the use of high loading of precious metal catalysts (4-10
45 mol% Pd or Rh) with the best TON of 25.10 Moreover, these
reactions employ complicated catalytic systems, and require a
sterically bulky group (usually a triisopropylsilyl group)11 to
prevent the coordinating of the alkyne unit with metal center.
Scheme 1. Ni-Catalyzed Alkynylation of (Hetero)aryl C –H
60 Bonds with Low Catalyst Loadings.
Herein, we disclose a versatile and efficient nickel-catalyzed
alkynylation of unactivated aromatic C-H bonds with
bromoalkynes (Scheme 1). The significance of this study is
threefold: 1) The reaction can proceed with as little as 0.5 mol%
65 of Ni(OTf)2, which equate to a substrate/catalyst (s/c) ratio of 200
and the highest turnover number (TON) up to 196. 2) The
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alkynylation reaction proceeds under a sustainable and simple
catalytic system without the need of expensive ligands and/or
metallic oxidants. 3) Chatani and coworkers have reported a
nickel-catalyzed oxidative alkynylation and intramolecular
annulations of arenes with internal alkynes employing a 2-
View Article Online
DOI: 10.1039/C5CC01163A
5
pyridinylmethylamine
auxiliary.14,15 Nonetheless,
nickel-
catalyzed alkynylation of unactivated C-H bonds has not yet been
realized. Therefore, this versatile system also highlights a new
mode of reaction catalyzed by nickel catalyst.
10
Our investigation was inspired by the elegant studies of Ni-
catalyzed C-H functionalization16-17 and recent advances on the
use of our newly developed bidentate directing group derived
from (pyridin-2-yl)isopropyl amine (PIP-amine) for C–H
functionalization reactions.18-20 We commenced our studies by
15 testing
the
reaction
of
benzamide
1a
with
(triisopropylsilyl)ethynyl bromide (2a). We were delighted to
find that the desired aryl alkyne 3a was obtained in moderate
yield when Ni(OTf)2 was used as catalyst and DME as ligand
(Table 1, entry 1, 60% yield). A thorough screening of solvents
20 showed that pivalonitrile can dramatically improve the yield and
afforded the expected product in good yield (entry 8, 81%). The
addition of NaHCO3 as base improved the catalytic efficiency
and gave almost quantitatively conversion of the starting material
(entry 9). Gratifyingly, the catalyst loading can be reduced to 0.5
25 mol% under the optimized reaction conditions with an increased
concentration of the reaction (entry 10, from 0.1 M to 0.8 M in
pivalonitrile, Condition A). It is worth noting that the mono- and
dialkynylation products could be selectively obtained by
adjusting the stoichiometry of 1a and bromoalkyne 2a. Thus,
30 when 4 equivalent of bromoalkyne 2a was used, dialkynylated
product 4a was isolated in 92% yield (entry 11, Condition B);
while monoalkynylation could be achieved in the presence of 2
equivalent of benzamide 1a (entry 12, Condition C). We then
examined the effect of various directing groups on the direct C-H
35 alkynylation and the PIP directing group gave the best results.21
Table 1. Optimization of the reaction conditionsa
Scheme 2. The scope of benzamides. Conditions A: 1 (0.4
mmol), 2a (0.8 mmol), Ni(OTf)2 (0.002 mmol, 0.5 mol%), DME
TIPS
O
o
45 (0.004 mmol), NaHCO3 (0.8 mmol), t-BuCN (0.5 mL), 150 C,
O
PIP
N
24 h, isolated yield. a0.2 mol% Ni(OTf)2.
O
Ni(OTf)2 (x mol%)
2.0 equiv base
PIP
H
N
PIP
H
H
+
N
H
1a
DME (2x mol%)
150 oC, 12 h, solvent
+
TIPS
TIPS
Br
TIPS
Following the optimized conditions, we next tested the scope
and limitation of this reaction. As shown in Scheme 2,
benzamides bearing both electron-donating and electron-
50 withdrawing groups at the ortho and meta positions of the phenyl
ring reacted smoothly with bromoalkyne 2a to give the expected
monoalkynylation product selectively in good yields. When meta-
substituted substrates was employed, the alkynylation tended to
occur at the sterically more accessible position, providing the
55 1,2,5-trisubstituted products in high yields regioselectively (3c,
3e, 3g and 3i). Importantly, a number of synthetically useful
functional groups, such as fluoro, trifluoromethyl, chloro, bromo
and methoxy, were all tolerated. Additionally, the alkynylation of
1- and 2-naphthamides also proceeded efficiently under the
60 optimized reaction conditions (1l and 1m). Alkynylation of
heteroarenes, such as nicotinamides (1n and 1o),
isonicotinamides (1p-1s) and thiophene-2-carboxamides (1t-1v),
also reacted efficiently with bromoalkyne 2a to give the
alkynylation products in high yields (3n-3v). Notably, halogen
65 groups, such as chloro and bromo, were also compatible with this
2a
3a
4a
entry x (mol%)
base
solvent (M)
yield (%)b
60% (3:1)
5%
15%
18%
1
2
3
4
5
6
7
8
10
10
10
10
10
10
10
10
10
0.5
0.5
0.5
Na2CO3 DCE (0.1)
Na2CO3 DME (0.1)
Na2CO3 DMSO (0.1)
Na2CO3 1,4-dioxane (0.1)
Na2CO3 isobutyronitrile (0.1) 75% (4:1)
Na2CO3 butyronitrile (0.1)
Na2CO3 MeCN (0.1)
Na2CO3 pivalonitrile (0.1)
NaHCO3 pivalonitrile (0.1)
NaHCO3 pivalonitrile (0.8)
NaHCO3 pivalonitrile (0.8)
NaHCO3 pivalonitrile (0.8)
16%
trace
81% (3:1)
99% (1:2)
99% (1:2.8)
92% (4a)c
90% (3a)c
9
10d
11e
12f
aReaction conditions: 1a (0.1 mmol), Ni(OTf)2 (x mol%), base (2 equiv), 2a (2 equiv)
and DME (2x mol%) at 150 oC for 12 h under N2. b1H NMR yield using CH2Br2 as
40 the internal standard. Isolated yield. d1a (0.4 mmol), 24 h. e1a (0.4 mmol), 2a (4
c
equiv), 24 h. f1a (0.8 mmol), 2a (0.4 mmol), 24 h, isolated yield based on 2a.
2
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Me
O
Me
O
protocol, providing useful handles for further elaborations. A
turnover number of 255 can be achieved with reduced yield when
0.2 mol% Ni(OTf)2 was used (3b, 51% yield).
The controllable functionalization of sterically and
electronically unbiased C-H bonds is a major challenge in nickel-
catalyzed C-H functionalization reactions. To our delight,
chemoselective synthesis of monoalkynylation product 3 and
dialkynylation product 4 could be achieved by simply adjusting
the ratio of benzamides 1 and bromoalkyne 2a (conditions B and
Ni(OTf)2 (5 mol%)
Br
PIP
PIP
N
N
+
H
H
NaHCO3, t-BuCN-DME
130 oC, 24 h, N2
H
R
View Article Online
R
DOI: 10.1039/C5CC01163A
1b
2
5
Me
O
Me
O
5
Me
O
PIP
PIP
Ph
PIP
N
N
N
H
H
H
TMS
5a, 72%
5b, 68%
5c, 64%
Me
O
Me
O
Me
O
10 C in Table 1, entries 11 and 12). A wide range of functional
groups, such as alkyl, methoxy, fluoro, chloro, bromo,
trifluoromethyl, nitro, cyano, acetyl and methoxycarbonyl were
survived and gave the mono- and dialkynylation products
respectively (Scheme 3A).22 Notably, meta-Fluoro substrate 1ag
15 reacted predominantly at the position adjacent to fluorine under
conditions C, perhaps due to enhanced kinetic acidity of the
corresponding C–H bond (Scheme 3B). When the alkynylation
reaction was conducted under Conditions B, dialkynylated
product 4ag was generated in high yield (98%).
PIP
PIP
PIP
N
H
N
H
N
H
Me
OMe
tBu
5d, 54%
5e, 65%
5f, 66%
Me
O
Me
O
PIP
PIP
N
N
H
H
( )n
Cl
n = 4, 5h, 62%
n = 7, 5i, 70%
5g, 60%
TIPS
Scheme 4. Scope of bromoalkynes. Reaction conditions: 1b (0.2
mmol), 2 (0.4 mmol), Ni(OTf)2 (0.01 mmol), DME (0.02 mmol),
NaHCO3 (0.4 mmol), t-BuCN (2 mL), 130 C, 24 h, isolated
O
O
H
O
Ni(OTf)2
(0.5 mol%)
Ni(OTf)2
(0.5 mol%)
PIP
PIP
PIP
N
N
N
o
A)
H
H
H
Conditions C
Conditions B
R
R
R
H
45 yield.
TIPS
TIPS
1a, 1w-1af
R = H, 3a, 90%
R = H, 4a, 92%
R = p-Me, 3w, 64%
R = p-OMe, 3x, 66%
R = p-F, 3y, 78%
R = p-Me, 4w, 55%
R = p-OMe, 4x, 67%
R = p-F, 4y, 90%
Finally, we further demonstrated the scalability of this
catalytic protocol by using Conditions A in Table 2 to prepare
1.44 g of 3a and 0.66 g 4a using only 10 mg of Ni(OTf)2
50 (Scheme 5a). It is worth noting that the PIP auxiliary can be
easily removed via a mild N-nitrosylation/hydrolysis sequence as
we have demonstrated recently, providng an expeditious access to
ortho-alkynylated benzoic acids (Scheme 5b).13
R = p-Cl, 3z, 83%
R = p-Cl, 4z, 96%
R = p-Br, 3aa, 72%
R = p-CF3, 3ab, 76%
R = p-NO2, 3ac, 80%
R = p-CN, 3ad, 72%
R = p-Ac, 3ae, 82%
R = p-CO2Me, 3af, 70%
R = p-Br, 4aa, 52%
R = p-CF3, 4ab, 97%
R = p-NO2, 4ac, 84%
R = p-CN, 4ad, 99%
R = p-Ac, 4ae, 82%
R = p-CO2Me, 4af, 90%
TIPS
O
O
H
F
O
Ni(OTf)2
(0.5 mol%)
Ni(OTf)2
(0.5 mol%)
PIP
PIP
PIP
N
N
H
N
B)
H
H
Conditions C
H
Conditions B
F
TIPS
3ag, 51%
F
TIPS
1ag
4ag, 98%
20
Scheme 3. Controllable Mono- and Di-alkynylation. Conditions
B: 1 (0.4 mmol), 2a (1.6 mmol), Ni(OTf)2 (0.002 mmol), DME
o
(0.004 mmol), NaHCO3 (0.8 mmol), t-BuCN (0.5 mL), 150 C,
24 h, isolated yield based on benzamide 1. Conditions C: 1 (0.8
25 mmol), 2a (0.4 mmol), Ni(OTf)2 (0.002 mmol), DME (0.004
o
mmol), NaHCO3 (0.8 mmol), t-BuCN (0.5 mL), 150 C, 24 h,
isolated yield based on bromoalkyne 2a.
55
Subsequently, we tested a variety of bromoalkynes and were
30 pleased to find that this alkynylation protocol was very efficient.
As shown in Scheme 4, both alkyl- and aryl-based alkynyl
bromides reacted smoothly with ortho-methyl benzamide 1b,
furnishing 5a-5i in generally good yields. The generality and
efficiency of the alkynylation reagents rendered this Ni-catalyzed
35 alkynylation synthetically more attractive than previously
reported Pd- and Rh-catalyzed alkynylation. The TMS-protected
bromoalkyne 2b was also tolerated, affording 5a in 72% yield.
Both electron-donating and electron-withdrawing substitutents
were compatible on the aryl ring of bromoalkynes (5d-5i).
Scheme 5. Gram-scale synthesis and removal of the PIP and
TIPS groups.
In conclusion, we have reported the use of a sustainable, easy
to handle catalytic system that is efficient for the direct
60 alkynylation of unactivated aryl C–H bonds employing a
removable auxiliary at low nickel loadings (0.5 mol%). This
reaction protocol surpasses previously reported alkynylation
reactions for broad substrate scope, cheap and simple catalyst
system, and high catalytic turnovers (up to 196; s/c = 200). The
65 highly efficient and scalable catalytic reaction proceeded with
excellent functional group compatibility under simple reaction
40
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M. Tobisu and N. Chatani, Synlett 2012, 2763; (e) J. He, M. Wasa, K. S.
L. Chan and J.-Q. Yu, J. Am. Chem. Soc. 2013, 135, 3387; (f) Y.-H. Xu,
Q.-C. Zhang, T. He, F.-F. Meng and T.-P. Loh, Adv. Synth. VCieawtaAlr.ti2c0le1O4n,line
systems, therefore representing a significant advantage in
transition-metal-catalyzed C-H alkynylation reactions.
65
356, 1539.
DOI: 10.1039/C5CC01163A
7.S. H. Kim, S. H. Park and S. Chang, Tetrahedron 2012, 68, 5162.
8.(a) C. Feng and T.-P. Loh, Angew. Chem. Int. Ed. 2014, 53, 2722; (b) C.
Feng, D. Feng and T.-P. Loh, Chem. Commun. 2014, 50, 9865; (c) C.
Feng, D. Feng, Y. L. T.-P. Loh, Org. Lett. 2014, 16, 5956.
70 9.(a) F. Xie, Z. Qi, S. Yu and X. Li, J. Am. Chem. Soc. 2014, 136, 4780;
(b) K. D. Collins, F. Lied and F. Glorius, Chem. Commun. 2014, 50,
4459.
Acknowledgements
Financial support from the National Basic Research Program of China
5 (2015CB856600), the NSFC (21422206, 21272206), the Fundamental
Research Funds for the Central Universities (2014QNA3008) and
Zhejiang Provincial NSFC (LZ12B02001) is gratefully acknowledged.
10. An exceptionally low palladium loading (0.2 mol% [Pd2(dba)3],
which equate to 0.4 mol% Pd) in direct alkynylation of heterocycles has
75
been reported by Su group, see ref. 5l.
11. Sporadic examples of alkynylation with tert-butyl-based alkynylation
reagents have been reported in ref 8a and 9a.
Notes and references
aDepartment of Chemistry, Zhejiang University, Hangzhou 310027, China.
10 E-mail: bfshi@zju.edu.cn
12. M. Shang, H.-L. Wang, S.-Z. Sun, H.-X. Dai and J.-Q. Yu, J. Am.
Chem. Soc. 2014, 136, 11590.
80 13. Y.-J. Liu, Y.-H. Liu, X.-S. Yin, W.-J. Gu and B.-F. Shi, Chem. Eur. J.
2015, 21, 205.
bState Key Laboratory of Bioorganic & Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
14. H. Shiota, Y. Ano, Y. Aihara, Y. Fukumoto and N. Chatani, J. Am.
Chem. Soc. 2011, 133, 14952..
† Electronic Supplementary Information (ESI) available: Detailed
15 experimental procedures, and analytical data for all new compounds, see
DOI: 10.1039/b000000x/
‡ 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.
20 1.For selected recent reviews, see: (a) G. Rouquet and N. Chatani, Angew.
Chem. Int. Ed., 2013, 52, 11726; (b) J. Yamaguchi, A. D. Yamaguchi
and K. Itami, Angew. Chem. Int. Ed. 2012, 51, 8960; (c) N. Kuhl, M. N.
Hopkinson, J. Wencel-Delord and F. Glorius, Angew. Chem. Int. Ed.
2012, 51, 10236; (d) K. Engle, T.-S. Mei, M. Wasa and J.-Q. Yu, Acc.
15. J. Dong, F. Wang and J. You, Org. Lett. 2014, 16, 2884.
85 16. (a) A. T. Higgs, P. J. Zinn, S. J. Simmons, and M. S. Sanford,
Organometallics 2009, 28, 6142; (b) Y. Aihara and N. Chatani, J. Am.
Chem. Soc. 2013, 135, 5308; (c) Y. Aihara and N. Chatani, J. Am. Chem.
Soc. 2014, 136, 898; (d) M. Li, J. Dong, X. Huang, K. Li, Q. Wu, F.
Song and J. You, Chem. Commun. 2014, 50, 3944; (e) W. Song, S.
Lackner and L. Ackermann, Angew. Chem. Int. Ed. 2014, 53, 2477; (f)
X. Wu, Y. Zhao and H. Ge, J. Am. Chem. Soc. 2014, 136, 1789; (g) X.
Wu, Y. Zhao and H. Ge, Chem. Eur. J. 2014, 20, 9530; (h) X. Cong, Y.
Li, Y. Wei and X. Zeng, Org. Lett. 2014, 16, 3926; (i) M. Iyanaga, Y.
Aihara and N. Chatani, J. Org. Chem. 2014, 79, 11933; (j) A. Yokota, Y.
Aihara and N. Chatani, J. Org. Chem. 2014, 79, 11922; (k) Y. Aihara,
M. Tobisu, Y. Fukumoto and N. Chatani, J. Am. Chem. Soc. 2014, 136,
15509; (l) S.-Y. Yan, Y.-J. Liu, B. Liu, Y.-H. Liu and B.-F. Shi, Chem.
Commun. 2015, 51, 4069.
17. For reviews and examples of Ni-catalyzed C-H functionalization of
electronically biased arenes and heteroarenes, see: (a) J. Yamaguchi, K.
Muto and K. Itami, Eur. J. Org. Chem. 2013, 19; (b) Y. Nakao, Chem.
Rec. 2011, 11, 242. And references therein.
18. (a) F.-J. Chen, S. Zhao, F. Hu, K. Chen, Q. Zhang, S.-Q. Zhang and
B.-F. Shi, Chem. Sci. 2013, 4, 4187; (b) Q. Zhang, K. Chen, W.-H. Rao,
Y.-J. Zhang, F.-J. Chen and B.-F. Shi, Angew. Chem. Int. Ed. 2013, 52,
13588; (c) Q. Zhang, X.-S. Yin, S. Zhao, S.-L. Fang and B.-F. Shi,
Chem. Commun. 2014, 50, 8353; (d) F.-J. Chen, G. Liao, X. Li, J. Wu
and B.-F. Shi, Org. Lett. 2014, 16, 5644.
19. For pioneer work of the use of bidentate auxiliary, see: (a) V. G.
Zaitsev, D. Shabashov and O. Daugulis, J. Am. Chem. Soc. 2005, 127,
13154; (b) D. Shabashov and O. Daugulis, J. Am. Chem. Soc. 2010, 132,
3965; (c) B. D. Dangel, K. Godula, S. W. Youn, B. Sezen and D. Sames,
J. Am. Chem. Soc. 2002, 124, 11856.
20. For selected examples, see: (a) C. P. Ting and T. J. Maimone, Angew.
Chem. Int. Ed. 2014, 53, 3115; (b) Z. Wang, J.-Z. Ni, Y. Kuninobu and
M. Kanai, Angew. Chem. Int. Ed. 2014, 53, 3496; (c) B. Urones, Á. M.
Martínez, R. Rodríguez, G. Arrayάs and J. Carretero, Chem. Commun.
2013, 49, 11044; (d) A. M. Suess, M. Z. Ertem, C. J. Cramer and S. S.
Stahl, J. Am. Chem. Soc. 2013, 135, 9797; (e) R. L. Ilies, A. Matsumoto
and E. Nakamura, J. Am. Chem. Soc. 2013, 135, 6030; (f) S.-Y. Zhang,
G. He, W. A. Nack, Y. Zhao, Q. Li and G. Chen, J. Am. Chem. Soc.
2013, 135, 2124; (g) M. Nishino, K. Hirano, T. Satoh and M. Miura,
Angew. Chem. Int. Ed. 2013, 52, 4457; (h) M. Shang, S.-Z. Sun, H.-X.
Dai and J.-Q. Yu, J. Am. Chem. Soc. 2014, 136, 3354.
90
25
Chem. Res. 2012, 45, 788; (e) P. B. Arockiam, C. Bruneau and P. H.
Dixneuf, Chem. Rev. 2012, 112, 5879; (f) C. Zhang, C. Tang and N.
Jiao, Chem. Soc. Rev. 2012, 41, 3464.; (g) L. Ackermann, Chem. Rev.
2011, 111, 1315; (h) C. L. Sun, B. J. Li and Z.-J. Shi, Chem. Rev. 2011,
111, 1293; (i) L. McMurray, F. O’Hara and M. J. Gaunt, Chem. Soc. Rev.
2011, 40, 1885; (j) D. A. Colby, R. G. Bergman and J. A. Ellman, Chem.
Rev. 2010, 110, 624; (k) T. W. Lyons and M. S. Sanford, Chem. Rev.
2010, 110, 1147; l) O. Daugulis, H.-Q. Do and D. Shabashov, Acc.
Chem. Res., 2009, 42, 1074; (m) A. R. Dick and M. S. Sanford,
Tetrahedron 2006, 62, 2439.
95
30
100
105
110
115
120
35 2.For selected examples of C-H functionalization at low catalyst loading,
see: (a) M. Dams, D. E. De Vos, S. Celen and P. A. Jacobs, Angew.
Chem. Int. Ed. 2003, 42, 3512; (b) K. M. Engle, D.-H. Wang and J.-Q.
Yu, J. Am. Chem. Soc. 2010, 132, 14137.
3.(a) K. Sonogashira, J. Organomet. Chem. 2002, 653, 46; (b) R. R.
40
Tykwinski, Angew. Chem. Int. Ed. 2003, 42, 1566; (c) E. I. Negishi and
L. Anastasia, Chem. Rev. 2003, 103, 1979; (d) R. Chinchilla and C.
Nάjera, Chem. Soc. Rev. 2011, 40, 5084.
4.(a) A. S. Dudnik and V. Gevorgyan, Angew. Chem. Int. Ed. 2010, 49,
2096; (b) J. P. Brand and J. Waser, Chem. Soc. Rev. 2012, 41, 4165.
45 5.For examples of alkynylation of electronically biased arenes and
heteroarens, see: (a) I. V. Seregin, V. Ryabova and V. Gevorgyan, J. Am.
Chem. Soc. 2007, 129, 7742; (b) F. Besselièvre and S. Piguel, Angew.
Chem. Int. Ed. 2009, 48, 9553; (c) N. Matsuyama, K. Hirano, T. Satoh
and M. Miura, Org. Lett. 2009, 11, 4156; (d) J. P. Brand, J. Charpentier
50
and J. Waser, Angew. Chem. Int. Ed. 2009, 48, 9346; (e) Y. Gu and X.
Wang, Tetrahedron Lett. 2009, 50, 763; (f) S. H. Kim and S. Chang,
Org. Lett. 2010, 12, 1868; (g) Y. Wei, H. Zhao, J. Kan, W. Su and M.
Hong, J. Am. Chem. Soc. 2010, 132, 2522; (h) T. Haro and C. Nevado,
J. Am. Chem. Soc. 2010, 132, 1512; (i) L. Yang, L. Zhao and C.-J. Li,
Chem. Commun. 2010, 46, 4184; (j) S. H. Kim, J. Yoon and S. Chang,
Org. Lett. 2011, 13, 1474; (k) S. Ding, Y. Yan and N. Jiao, Chem.
Commun. 2013, 49, 4250; (l) X. Jie, Y.; Shang, P. Hu and W. Su, Angew.
Chem. Int. Ed. 2013, 52, 3630.
55
125 21. See the Supporting Information for details.
22. F. Diederich, P. J. Stang and R. R Tykwinski, Acetylene Chemistry:
Chemistry, Biology and Material Science, Wiley-VCH, Weinheim, 2005.
6.(a) M. Tobisu, Y. Ano and N. Chatani, Org. Lett. 2009, 11, 3250; (b) Y.
Ano, M. Tobisu and N. Chatani, J. Am. Chem. Soc. 2011, 133, 12984; (c)
Y. Ano, M. Tobisu and N. Chatani, Org. Lett. 2012, 14, 354; (d) Y. Ano,
60
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DOI: 10.1039/C5CC01163A
A sustainable and simple catalytic system for the atom-economical alkynylation of benzamides with low nickel loadings is described.
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