Pd(TFA)2-catalyzed oxidative coupling of anilides with olefins through C[sbnd]H bond activation under non-acidic conditions

Article abstract of DOI:10.1016/j.jorganchem.2016.08.025

C[sbnd]H bond activation is an important issue. The Pd-catalyzed and non-coordinating anion improved C[sbnd]H bond activation was realized through the oxidative coupling reaction of anilides with olefins under non-acidic conditions. Additionally, the cata

Full text of DOI:10.1016/j.jorganchem.2016.08.025

Journal of Organometallic Chemistry 822 (2016) 100e103
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Pd(TFA)2-catalyzed oxidative coupling of anilides with olefins through
CeH bond activation under non-acidic conditions
Xiaoli Yu, Wei Yao, Huida Wan, Zhaojun Xu, Dawei Wang*
The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi,
214122, China
a r t i c l e i n f o
a b s t r a c t
Article history:
CeH bond activation is an important issue. The Pd-catalyzed and non-coordinating anion improved CeH
bond activation was realized through the oxidative coupling reaction of anilides with olefins under non-
acidic conditions. Additionally, the catalytic activity of palladium catalysts is enhanced by non-
coordinating anions, further proving that non-coordinating anion can be used in palladium-involved
reactions.
Received 29 June 2016
Received in revised form
4 August 2016
Accepted 23 August 2016
Available online 24 August 2016
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Palladium
Non-coordinating anion
Anilides
Non-acidic
Coupling
1. Introduction
et al. reported the cycloaddition of benzamides and alkynes
through Rh-catalyzed CeH activation [7]. Ackermann et al. showed
Very weakly coordinating anions (WCAs) and non-coordinating
anions (NCAs) are an important topic and sometimes they have
important effects in modern organic chemistry and medical syn-
thesis [1]. In the past, many transformations and reactions were
explored through the help of WCAs and NCAs [2]. Recently, we
found and verified that the catalytic activity of rhodium catalyst is
obviously improved and changed by non-coordinating anions,
which provide an efficient method that allows the rhodium to
become a good chemoselectivity catalyst in selective CeH bond
activation of anilides [3].
The past twenty years evidenced the extremely rapid develop-
ment of CeH activation, which has been considered to be one of the
most efficient methods in modern organic chemistry and medical
synthesis, because it provides an atom and step-economical path to
the many natural products or intermediates [4]. One typical model
is anilides, particularly in the study of CeH activation with Pd, Rh,
Ru as a catalyst (Scheme 1) [5]. An early important example is the
Pd-catalyzed ortho CeH bond activation of anilides developed by
de Vries and van Leeuwen with acid as solvent [6]. Recently, Rovis
the alkenylations of anilides and benzamides with water as solvent
[8]. Based on these excellent examples and results (Chang [9],
Fagnou [10], Glorius [11], Cui [12], Li [13], Shi [14], Ge [15], Yu [16],
Ma [17], Chatani [18] and others [19]), herein, we found that NCAs
could still promote Pd-catalyzed CeH bond activation of anilides
with moderate yields under non-acidic conditions. This trans-
formation could proceed under non-acidic conditions and thus
acid-sensitive functional groups can be tolerated during the reac-
tion, which provides an much milder reaction conditions for the
simplifying workup procedures and has better adaptability to the
environment.
2. Results and discussion
Recently, we reported the Rh-catalyzed selective CeH bond
activation of diaryl substituted anilides, which revealed that N-aryl
ring product was discovered under non-coordinating anion con-
ditions, while C-aryl ring product was obtained in the absence of
non-coordinating anion with rhodium as a catalyst [3]. When
palladium was used as a catalyst, only N-aryl ring product was
achieved with (or without) non-coordinating anion conditions,
which is very different to our previous results (Scheme 2). The
obvious difference was that the yield was enhanced under non-
* Corresponding author.
E-mail address: wangdw@jiangnan.edu.cn (D. Wang).
http://dx.doi.org/10.1016/j.jorganchem.2016.08.025
0022-328X/© 2016 Elsevier B.V. All rights reserved.

X. Yu et al. / Journal of Organometallic Chemistry 822 (2016) 100e103
101
Table 1
Screening of reaction conditions.a
Entry
Catalyst
Oxidant
Solvent
Yield [%]b
1c
2c
3c
4c
5c
6
7
8
9
10
11
12
13
14
15
16
Pd(PPh3)2Cl2
Pd/C
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
TBHP
DMF
DMF
<5
<5
<5
17
31
65
<5
27
19
48
36
53
44
11
<5
<5
Pd(OAc)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
Scheme 1. CeH Activation with Anilides as Directing Group.
TBHP
K2S2O8
Ag2CO3
Cu(OAc)2
K2Cr4O7
MnO2
mCPBA
TBHP
TBHP
Dioxane
THF
DMF
TBHP
TBHP
a
Conditions: 1a (0.50 mmol, 1.0 equiv.), 2a (0.70 mmol, 1.4 equiv.), [Pd] (5%),
AgOTf (25%), oxidant (1.5 equiv.), solvent (3 mL), reflux, 24 h.
b
Isolated yields.
Without AgOTf.
c
Scheme 2. The CeH activation with non-coordinating anions and different catalyst.
coordinating anion conditions. As the continuing research about
the non-coordinating anion to CeH bond activation in our group
[3,20], we seek to discern the details of this transformation with
palladium as a catalyst under non-acidic conditions.
obtained with a slightly low yield, which revealed that this trans-
formation does not constitute radical progress (Scheme 4). How-
ever, the reaction mechanism for this transformation is not yet
clear.
Concurrently, in order to demonstrate this clearly, the substrate
1a-d5 was used to test the reaction. The results showed that only
3a-d4 was achieved at 21% yield, while 4a-d5 was not found.
Therefore, this clearly revealed that only the N-aryl ring product
was obtained with palladium as a catalyst (Scheme 3).
Furthermore, in order to better under reaction mechanism, the
kinetic isotope effects (KIE) experiments were carried out. It was
found that the KIE (KH/KD ¼ 3.17) was observed from the isotope
Next, the screening reaction conditions were carried out to
obtain a better yield. The results showed that the best reaction was
achieved in toluene with TBHP as the oxdidant (Table 1).
Table 2
Substrate expansion experiment.a
Thus, with the best reaction conditions in hand, we explored the
scope of the CeH bond activation reaction of anilides with ester
acrylate. The results are summarized in Table 2. Generally, all the
anilides were converted into the corresponding products with
moderate to good yields. The anilides with various electron-
donating groups could be worked well to produce the corre-
sponding products.
Entry
R1
R2
R3
Yield [%]b
To unambiguously elucidate this reaction, a preliminary mech-
anism exploration was conducted. TEMPO (2,2,6,6-tetramethyl-1-
piperidinyloxy) was thought to be an effective radical scavenger
with which to check the reaction pathway. Thus, the control reac-
tion for the CeH bond activation reaction of anilides with ester
acrylate was carried on under 1.0 equiv of TEMPO amid optimized
conditions. The result showed that the corresponding product was
1
2
3
4
5
6
7
8
H
Me
F
CF3
Cl
H
p-Me-Ph
Ph
Ph
Ph
Et
Et
Me
Me
Me
Et
Et
Me
Et
65 (3a)
71 (3b)
67 (3c)
70 (3d)
65 (3e)
74 (3f)
68 (3g)
85 (3h)
78 (3i)
66 (3j)
82 (3k)
76 (3l)
64 (3m)
77 (3n)
73 (3o)
78 (3p)
Ph
p-OMe-Ph
Ph
Ph
Ph
Ph
p-OMe-Ph
p-NO2- Ph
P-OMe-Ph
Me
Me
Me
H
OMe
OMe
Cl
NO2
OMe
H
F
Cl
OMe
9
10
11
12
13
14
15
16
Et
Me
Me
Me
Me
Me
Me
a
Conditions: 1 (0.50 mmol, 1.0 equiv.), 2 (0.70 mmol, 1.4 equiv.), Pd(TFA)2 (5%),
AgOTf (25%), TBHP (1.5 equiv.), toluene (3 mL), 24 h.
b
Scheme 3. Deuteration experiments.
Isolated yields.

102
X. Yu et al. / Journal of Organometallic Chemistry 822 (2016) 100e103
(entries 3, 10e12). Importantly, when NaOTf was used to this re-
action, almost the same result was achieved (entry 13).
3. Conclusions
In summary, the Pd-catalyzed and non-coordinating anion
improved CeH bond activation was realized through the oxidative
coupling reaction of anilides with olefins under non-acidic condi-
tions. Additionally, the catalytic activity of palladium catalysts is
enhanced by non-coordinating anions, which provide further proof
that non-coordinating anion can be used in palladium-involved
reactions.
Scheme 4. Control experiments.
experiment (Scheme 5). This revealed that the radical reaction
process is not involved in this reaction.
The “silver effect” in gold catalysis was disclosed by the Shi
group in 2012, which led to the reconsideration of some silver-
involved reactions [21]. Many transformations involving silver
actually consist of silver-assisted metal catalysis or bimetallic
catalysis. In some cases, AgCl or silver nanoparticles may play a
decisive role. Based on this consideration, we conducted a series of
“silver effect” experiments and the results were concluded in
Table 3. The experiments showed that the reaction didn't occur
only with AgOTf conditions. Sodium chloride has no effect in this
reaction (Table 3, entry 8). Nearly the same yield was achieved,
when the catalyst was carefully filtered with a pad of paper in order
to remove the AgCl. This revealed that non-coordinating anions
slightly improved catalytic activity of palladium catalysts, while
silver does not play a role in this transformation. It should be noted
that other non-coordinating anions produced different results
4. Experimental section
4.1. General experiments
The obtained products were characterized by 1H NMR spectra.
NMR spectra were obtained on Bruker Advance 400 and -300;
Chemical shifts were reported in parts per million (ppm,
downfield from tetramethylsilane. Proton coupling patterns are
described as singlet (s), doublet (d), triplet (t), multiplet (m); TLC
was performed using commercially prepared 100e400 mesh silica
gel plates (GF254), and visualization was effected at 254 nm; All the
reagents were purchased from commercial sources (J&KChemic,
TCI, Fluka, Acros, SCRC), and used without further purification.
d)
4.2. Typical procedure for the synthesis of compound 3a
The mixture of 4-methyl-N-phenylbenzamide (1a) (0.5 mmol),
ethyl acrylate (2a) (0.7 mmol), AgOTf (25 mol%) and TBHP (1.5
equiv.) in toluene (3 mL) was stirred at 120 ꢀC under air for 24 h.
Upon completion, the reaction mixture was removed the solvents
to give the residue. The residue was then purified by column
chromatography on silica gel (ethyl acetate/petroleum
ether ¼ 1:10) to provide the corresponding product as white solid
Scheme 5. The isotope effect experiments.
3a. 1H NMR (400 MHz, CDCl3)
d 8.02 (s, 1H), 7.91e7.85 (m, 2H), 7.82
(d, J ¼ 8.4 Hz, 2H), 7.60 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.47e7.40 (m, 1H),
Table 3
7.29 (d, J ¼ 8.0 Hz, 2H), 7.25 (t, J ¼ 7.6 Hz, 1H), 6.43 (d, J ¼ 16.0 Hz,
The “silver effect” test experiments.a,b
1H), 4.24 (q, J ¼ 7.2 Hz, 2H), 2.44 (s, 3H), 1.32 (t, J ¼ 7.0 Hz, 3H). 13
C
NMR (101 MHz, CDCl3) d 166.8,166.1,142.8,139.5,136.2,131.6,131.0,
129.6, 128.1, 127.4, 126.0, 125.4, 121.0, 60.8, 21.7, 14.4. IR (KBr): 3265,
2988,1712,1647,1614,1521,1506, 1482,1449,1368,1315,1301,1261,
1178, 1032, 987, 864, 762 cmꢁ1
.
Acknowledgements
Entry
Catalyst
Conditions
3a:4a[%]
We gratefully acknowledge financial support of this work by the
National Natural Science Foundation of China (21401080), the
Natural Science Foundation of Jiangsu Province of China
(BK20130125), Jiangsu Talents Project (2013-JNHB-027), the
Fundamental Research Funds for the Central Universities (JUSRP
51627B) and MOE & SAFEA for the 111 Project (B13025).
1
2
3
4
5
6
7
none
0:0
e
e
e
e
e
e
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2/AgOTf
AgOTf
0:58
0:93b
88:0
0:0
Pd(TFA)2
38:0
65:0
Appendix A. Supplementary data
Pd(TFA)2/AgOTf
e
8
9
10
Pd(TFA)2/AgOTf/NaCl
Pd(TFA)2/AgOTf/NaCl
Pd(TFA)2/AgBF4
No filtration
After filtration
65:0
61:0
47:0
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2016.08.025.
e
e
e
e
11
12
13
Pd(TFA)2/AgSbF6
Pd(TFA)2/AgNTf2
Pd(TFA)2/NaOTf
31:0
54:0
63:0
References
[1] (a) C. Reed, Acc. Chem. Res. 31 (1998) 133;
a
Conditions: 1 (0.5 mmol, 1.0 equiv.), 2 (0.70 mmol, 1.4 equiv.), Pd(TFA)2 or
[Cp*RhCl2]2 (5%), AgOTf (25%), oxidant (1.5 equiv.), toluene or DCE (3 mL), 24 h,
isolated yields.
(b) E.Y.-X. Chen, T.J. Marks, Chem. Rev. 100 (2000) 1391;
(c) I. Krossing, I. Raabe, Angew. Chem. Int. Ed. 43 (2004) 2066.
[2] P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, Wiley-VCH, 2003.
[3] D. Wang, X. Yu, X. Xu, B. Ge, X. Wang, Y. Zhang, Chem. Eur. J. 22 (2016) 8663.
b
CH3CN was used.

X. Yu et al. / Journal of Organometallic Chemistry 822 (2016) 100e103
103
[4] (a) C. Sun, B. Li, Z. Shi, Chem. Rev. 111 (2010) 1293;
(b) M.P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 110 (2010) 704;
(c) T. Lyons, M. Sanford, Chem. Rev. 110 (2010) 1147;
(d) P. Arockiam, C. Bruneau, P. Dixneuf, Chem. Rev. 112 (2012) 5879;
(e) I. Mkhalid, J. Barnard, T. Marder, J. Murphy, J. Hartwig, Chem. Rev. 110
(2010) 890;
(f) G. Rouquet, N. Chatani, Angew. Chem. Int. Ed. 52 (2013) 11726;
(g) L. Ackermann, Chem. Res. 47 (2014) 281.
[5] (a) X. Wan, Z. Ma, B. Li, K. Zhang, S. Cao, S. Zhang, Z. Shi, J. Am. Chem. Soc. 128
(2006) 16;
[14] (a) S.-Y. Yan, Y.-J. Liu, B. Liu, Y.-H. Liu, B.-F. Shi, Chem. Commun. 51 (2015)
4069;
(b) Y.-J. Liu, Y.-H. Liu, S.-Y. Yan, B.-F. Shi, Chem. Commun. 51 (2015) 6388;
(c) S.-Y. Yan, Y.-J. Liu, B. Liu, Y.-H. Liu, Z.-Z. Zhang, B.-F. Shi, Chem. Commun. 51
(2015) 7341;
(d) Y.-H. Liu, Y.-J. Liu, S.-Y. Yan, B.-F. Shi, Chem. Commun. 51 (2015) 11650.
[15] (a) X. Wu, Y. Zhao, H. Ge, J. Am. Chem. Soc. 136 (2014) 1789;
(b) X. Wu, Y. Zhao, H. Ge, J. Am. Chem. Soc. 137 (2015) 4924.
[16] X.-C. Wang, Y. Hu, S. Bonacorsi, Y. Hong, R. Burrell, J.-Q. Yu, J. Am. Chem. Soc.
135 (2013) 10326.
(b) S. Yang, B. Li, X. Wan, Z. Shi, J. Am, Chem. Soc. 129 (2007) 6066;
(c) J.-R. Wang, C.-T. Yang, L. Liu, Q.-X. Guo, Tetrahedron Lett. (2007) 5449;
(d) K.D. Hesp, R.G. Bergman, J.A. Ellman, J. Am. Chem. Soc. 133 (2011) 11430;
(e) B.-J. Li, H.-Y. Wang, Q.-L. Zhu, Z.-J. Shi, Angew. Chem. Int. Ed. 51 (2012)
3948;
(f) L. Zhou, W. Lu, Org. Lett. 16 (2014) 508;
(g) X.-Q. Hao, L.-J. Chen, B. Ren, L.-Y. Li, X.-Y. Yang, J.-F. Gong, J.-L. Niu, M.-
P. Song, Org. Lett. 16 (2014) 1104;
[17] R. Zeng, C. Fu, S. Ma, J. Am. Chem. Soc. 134 (2012) 9597.
[18] (a) H. Shiota, Y. Ano, Y. Aihara, Y. Fukumoto, N. Chatani, J. Am. Chem. Soc. 133
(2011) 14952;
(b) G. Rouquet, N. Chatani, Chem. Sci. 4 (2013) 2201;
(c) L.C.M. Castro, N. Chatani, Chem. Eur. J. 20 (2014) 4548;
(d) Y. Aihara, N. Chatani, J. Am. Chem. Soc. 136 (2014) 898;
(e) A. Yokota, Y. Aihara, N. Chatani, J. Org. Chem. 79 (2014) 11922;
(f) K. Shibata, N. Chatani, Org. Lett. 16 (2014) 5148.
(h) X. Peng, W. Wang, C. Jiang, D. Sun, Z. Xu, C.-H. Tung, Org. Lett. 16 (2014)
5354;
[19] (a) Y. Wu, B. Li, F. Mao, X. Li, F.Y. Kwong, Org. Lett. 13 (2011) 3258;
(b) L.L. Chang, J. Zhang, J. Yang, M. Amoura, J.Y. Ying, Adv. Synth. Catal. 353
(2011) 2988;
(i) J. Yi, L. Yang, C. Xia, F. Li, J. Org. Chem. 80 (2015) 6213;
(j) Y. Hoshino, Y. Shibata, K. Tanaka, Adv. Synth. Catal. 356 (2014) 1577;
(k) Y. Takahama, Y. Shibata, K. Tanaka, Chem. Eur. J. 21 (2015) 9053.
[6] M.D.K. Boele, G.P.F. van Strijdonck, A.H.M. de Vreis, P.C.J. Kamer, J.G. Vries,
P.W.N.M. van Leeuwen, J. Am. Chem. Soc. 124 (2002) 1586.
[7] T.K. Hyster, T. Rovis, J. Am. Chem. Soc. 132 (2010) 10565.
[8] (a) L. Ackermann, L. Wang, R. Wolfram, A.V. Lygin, Org. Lett. 14 (2012) 728;
(b) W. Song, S. Lackner, L. Ackermann, Angew. Chem. Int. Ed. 53 (2014) 2477;
(c) H.H.A. Mamari, E. Diers, L. Ackermann, Chem. Eur. J. 20 (2014) 9739;
(d) A. Bechtoldt, C. Tirler, K. Raghuvanshi, S. Warratz, C. Kornhaaß,
L. Ackermann, Angew. Chem. Int. Ed. 55 (2016) 264.
[9] K. Shin, Y. Baek, S. Chang, Angew. Chem. Int. Ed. 52 (2013) 8031.
[10] (a) D.R. Stuart, M. Bertrand-Laperle, K.M.N. Burgess, K. Fagnou, J. Am. Chem.
Soc. 130 (2008) 16474;
(b) N. Guimond, C. Gouliaras, K. Fagnou, J. Am. Chem. Soc. 132 (2010) 6908.
[11] (a) F. Patureau, F. Glorius, J. Am. Chem. Soc. 132 (2010) 9982;
(b) F.W. Patureau, T. Besset, F. Glorius, Angew. Chem. Int. Ed. 50 (2011) 1064;
(c) S. Rakshit, C. Grohmann, T. Besset, F. Glorius, J. Am. Chem. Soc. 133 (2011)
2350.
(c) Y. Wu, P.Y. Choy, F. Mao, F.Y. Kwong, Chem. Commun. 49 (2013) 689;
(d) A. Cajaraville, S. Lopez, J.A. Varela, C. Saa, Org. Lett. 15 (2013) 4576;
(e) T.A. Davis, T.K. Hyster, T. Rovis, Angew. Chem. Int. Ed. 52 (2013) 14181;
(f) T.K. Hyster, K.E. Ruhl, T. Rovis, J. Am. Chem. Soc. 135 (2013) 5364;
(g) Q. Tang, D. Xia, X. Jin, Q. Zhang, X.-Q. Sun, C. Wang, J. Am. Chem. Soc. 135
(2013) 4628;
(h) N. Quinones, A. Seoane, R. Garcia-Fandino, J.L. Mascarenas, M. Gulias,
Chem. Sci. 4 (2013) 2874;
(i) J. Kim, Y. Moon, S. Lee, S. Hong, Chem. Commun. 50 (2014) 3227;
(j) R.K. Chinnagolla, M. Jeganmohan, Chem. Commun. 50 (2014) 2442;
(k) R. Manikandan, M. Jeganmohan, Org. Lett. 16 (2014) 912;
(l) S. Manna, A.P. Antonchick, Angew. Chem. Int. Ed. 53 (2014) 7324;
(m) S. Allu, K.C.K. Swamy, J. Org. Chem. 79 (2014) 3963;
(n) Z.-W. Chen, Y.-Z. Zhu, J.-W. Ou, Y.-P. Wang, J.-Y. Zheng, J. Org. Chem. 79
(2014) 10988.
[20] (a) D. Wang, B. Ge, L. Li, J. Shan, Y. Ding, J. Org. Chem. 79 (2014) 8607;
(b) D. Wang, K. Zhao, C. Xu, H. Miao, Y. Ding, ACS Catal. 4 (2014) 3910;
(c) D. Wang, X. Yu, W. Yao, W. Hu, C. Ge, X. Shi, Chem. Eur. J. 22 (2016) 5543;
(d) Y. Yang, A. Qin, K. Zhao, D. Wang, X. Shi, Adv. Synth. Catal. 358 (2016)
1443.
[12] (a) S. Cui, Y. Zhang, Q. Wu, Chem. Sci. 4 (2013) 3421;
(b) S. Cui, Y. Zhang, D. Wang, Q. Wu, Chem. Sci. 4 (2013) 3912.
[13] (a) F. Wang, G. Song, X. Li, Org. Lett. 12 (2010) 5430;
(b) G. Song, D. Chen, C.-L. Pan, R.H. Crabtree, X. Li, J. Org. Chem. 75 (2010)
7487.
[21] D. Wang, R. Cai, S. Sharma, J. Jirak, S.K. Thummanapelli, N.G. Akhmedov,
H. Zhang, X. Liu, J. Petersen, X. Shi, J. Am. Chem. Soc. 134 (2012) 9012.