Cobalt(III)-Catalyzed C-C Coupling of Arenes with 7-Oxabenzonorbornadiene and 2-Vinyloxirane via C-H Activation

Article abstract of DOI:10.1021/acs.orglett.6b01806

Co(III)-catalyzed mild C-C couplings of arenes with strained rings such as 7-oxabenzonorbornadienes and 2-vinyloxirane have been realized. The transformation is proposed to undergo ortho C-H activation, olefin insertion, and subsequent β-oxygen eliminatio

Full text of DOI:10.1021/acs.orglett.6b01806

Letter
pubs.acs.org/OrgLett
Cobalt(III)-Catalyzed C−C Coupling of Arenes with
7‑Oxabenzonorbornadiene and 2‑Vinyloxirane via C−H Activation
Lingheng Kong,†,‡ Songjie Yu,† Guodong Tang,† He Wang,† Xukai Zhou,†,‡ and Xingwei Li*,†
†Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
‡University of Chinese Academy of Sciences, Beijing 100049, China
S
* Supporting Information
ABSTRACT: Co(III)-catalyzed mild C−C couplings of
arenes with strained rings such as 7-oxabenzonorbornadienes
and 2-vinyloxirane have been realized. The transformation is
proposed to undergo ortho C−H activation, olefin insertion,
and subsequent β-oxygen elimination. A broad range of
synthetically useful functional groups are compatible, thus providing a new entry to access diversely 2-functionalized indoles.
Scheme 1. Allylation of Arenes
ver the past decades, transition-metal-catalyzed direct C−
OH functionalization and C−C/C−heteroatom bond
formation have received increasing attention because of their
high activity, broad substrate scope, and functional group
compatibility. This strategy has enabled the development of a
plethora of useful synthetic methods to access complex
structures.1 Despite these attractive features, most of the
achievements have been accomplished with expensive second-
and third-row transition-metal catalysts, particularly ruthenium,
rhodium, and palladium complexes. Thus, the development of
comparable and even more efficient systems with earth-
abundant first-row transition-metal catalysts is highly desirable.
Recently, Matsunaga and Kanai pioneered applications of high-
valent Cp*Co(III) complexes2 as earth-abundant and less toxic
metal catalysts for C−H activation of arenes. The high
efficiency originated from the higher Lewis acidity of the
Co(III) and enhanced metal−substrate corporation.3 After-
ward, the groups of Glorius,4 Ackermann,5 Ellman,6 Daugulis,7
Chang,8 and others9 have made progress in Co(III) catalysis.
Allylation of arenes is one of the most fundamental and
useful transformations in organic synthesis because the allyl
moiety can be further converted into a wide variety of
functional groups.10 Allylarenes are traditionally prepared by
rearrangements and electrophilic and nucleophilic substitutions.
These methods often suffer from harsh reaction conditions, low
regioselectivity, overallylation, and limited substrate scope.11
Therefore, the development of inexpensive and efficient
methods for the direct allylation of arenes in a green and
atom-economical fashion is highly desirable. In this regard,
transition-metal-catalyzed C−H bond functionalization has
exhibited tremendous potential for the direct allylation of
aromatic C−H bonds (Scheme 1a).12 These reactions are
thought to proceed via C−H metalation, olefin insertion, and
subsequent β-elimination of oxygen-containing functional
groups. However, the leaving groups lower the atom economy
of the reactions. To overcome this limitation, our group
developed an allylarene synthesis via Rh(III)-catalyzed C−H
activation of arenes and coupling with vinyloxirane (Scheme
1b).13 Lately, Ackermann and co-workers reported a cobalt-
(III)-catalyzed coupling of indoles and vinylcyclopropane via
C−H/C−C functionalization (Scheme 1c).14 In this process,
olefin insertion into a Rh−C bond is followed by β-C
elimination under exceedingly mild conditions. As part of our
ongoing studies and expansion of the utility of Cp*Co(III)
catalysis, we now report the Co(III)-catalyzed coupling of
indoles with 7-oxabenzonorbornadienes and 2-vinyloxirane to
access 2-substituted indoles.
At the outset of our study, we examined the C−H arylation
of N-pyrimidinylindole (1a) with 7-oxabenzonorbornadiene
(2a), which has been applied as a naphthylating reagent by us
under Rh(III) catalysis.13a When the reaction was conducted in
DCE using [Cp*CoCl2]2/AgSbF6 (4 mol %/16 mol %) as the
catalyst at 50 °C, traces of product were obtained (Table 1,
Received: June 21, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01806
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
Scheme 2. Dehydrative Coupling with 7-
a b
,
Oxabenzonorbornadienes
b
entry
cat. (mol %)
additive (mol %)
solvent
yield (%)
1
2
[Cp*CoCl2]2 (4)
[Cp*CoCl2]2 (4)
[Cp*CoCl2]2 (4)
[Cp*CoCl2]2 (4)
[Cp*CoCl2]2 (5)
[Cp*CoCl2]2 (5)
[Cp*CoCl2]2 (5)
[Cp*CoCl2]2 (4)
[Cp*CoCl2]2 (5)
[Cp*CoCl2]2 (5)
[Cp*CoCl2]2 (5)
−
AgSbF6 (16)
AgSbF6 (16)
AgSbF6 (16)
AgNTf2 (16)
AgSbF6 (16)
AgSbF6 (20)
AgSbF6 (30)
AgSbF6 (30)
AgSbF6 (30)
AgSbF6 (30)
AgSbF6 (30)
AgSbF6 (30)
AgSbF6 (30)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
dioxane
THF
TFE
<5
56
45
51
67
75
81
70
71
42
56
0
c
3
4
5
6
7
8
9
10
11
12
DCE
DCE
d
13
[Cp*CoCl2]2 (5)
52
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), HOAc (2
b
a
equiv), solvent (2 mL), 50 °C, 12 h, pressure tube under N2. Isolated
Reaction conditions: indole (0.2 mmol), 7-oxabenzonorbornadiene
c
d
yields after chromatography. PivOH (2 equiv) was used. 9-
(Toluene-4-sulfonyl)-1,4-dihydro-1,4-epiazanonaphthalene (2 equiv)
was used
(0.4 mmol), [Cp*CoCl2]2 (5 mol %), AgSbF6 (30 mol %), HOAc (2
b
equiv), DCE (2 mL), 50 °C, 12 h, pressure tube under N2. Isolated
c
yields after chromatography are shown. AgOAc (30 mol %), 110 °C.
ab
,
Scheme 3. C−H Allylation of Heterocycles
entry 1). Fortunately, the product 3aa was isolated in 56% yield
when HOAc (2 equiv) was introduced (entry 2). Switching the
acid to HOPiv lowered the yield to 45% (entry 3). The amount
of the silver additive had a significant effect on the reaction
efficiency. The isolated yield of 3aa was dramatically improved
to 81% when the ratio of AgSbF6 to [Cp*CoCl2]2 was
increased to 6:1 (entry 7), where the excess of AgSbF6 likely
activates the 7-oxabenzonorbornadiene substrate as a Lewis
acid.13a Solvent screening revealed that DCE was the most
optimal medium (entries 9−11). No product was observed
when the cobalt catalyst was omitted (entry 12). The product
was also obtained using 9-(toluene-4-sulfonyl)-1,4-dihydro-1,4-
epiazanonaphthalene in 52% yield (entry 13). While a Co(III)
catalyst is not unique for this reaction, the Rh(III)-catalyzed
system required a temperature of 130 °C,13a indicating the
higher efficiency of the Co(III) catalyst.
With the set of optimized reaction conditions in hand, the
scope and limitations of this reaction were next explored
(Scheme 2). Much to our delight, N-pyrimidinylindoles bearing
both electron-donating and -withdrawing substituents, includ-
ing methyl (3ba, 3ga, and 3la), methoxy (3ca and 3ha),
benzyloxy (3da), an ester group (3ea, 3ia, and 3ma), fluoro
(3ja), chloro (3ka and 3na), and bromo (3fa) at different
positions all coupled smoothly with 7-oxabenzonorbornadiene,
and the corresponding products were isolated in 53−84% yield.
Unfortunately, the introduction of substituents at the 3- and 7-
positions of the indole inhibited the reaction as a result of steric
hindrance. When a catalytic amount of AgOAc was added and
the temperature was raised, 3oa was obtained in 53% yield.
Similarly, the diarylation product 3pa was isolated in a
moderate yield (67%) when a 3-substituted indole substrate
was used. Naphthylated products 3ab and 3ac were also
isolated in moderate yields when substituted 7-oxabenzonor-
bornadienes were used.
a
Reaction conditions: indole (0.2 mmol), 2-vinyloxirane (0.4 mmol),
[Cp*Co(MeCN)3](SbF6)2 (5 mol %), NaOAc (20 mol %), DCE (2
mL), 40 °C, 12 h, pressure tube under N2. Isolated yields after
chromatography are shown.
b
large variety of electron-donating (Me, OMe, and OBn) and
-withdrawing (F, Cl, Br, and COOMe) groups in the benzene
ring all coupled smoothly with 2-vinyloxirane in excellent
yields. Of note, only a 5 mol % loading of the monomeric
Co(III) catalyst sufficed. The introduction of substituents at the
3- and 7-positions of the indole ring and on the pyrimidine ring
had minimal influence (5b, 5p, 5q, and 5r), indicative of
tolerance of steric effects, and the coupled products were
isolated in consistently excellent yields (92−98%). In all cases,
With the development of these dehydrative naphthylation
reactions, we next extended the strained olefins to 2-
vinyloxirane (Scheme 3). N-(2-Pyrimidyl)indoles bearing a
B
DOI: 10.1021/acs.orglett.6b01806
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the stereoselectivity of the reaction was low (trans/cis = 2.6:1−
3.2:1).
The arene substrate was not restricted to N-(2-pyrimidyl)-
indoles (Scheme 4). The coupling of 2-phenylpyridine and
a b
,
Scheme 4. Substrate Scope of Other Arenes
Scheme 5. Proposed Mechanism of Naphthylation
a
Arene (0.2 mmol), 2-vinyloxirane (0.4 mmol), [Cp*Co(MeCN)3]-
(SbF6)2 (5 mol %), NaOAc (20 mol %), DCE (2 mL), 60 °C, 12 h,
b
pressure tube under N2. Isolated yields after chromatography are
c
shown. The reaction was conducted at 100 °C.
benzo[h]quinoline with 2-vinyloxirane delivered allylic alcohols
7a and 7b, respectively, in good yields. Although this coupling
has been reported using Rh(III) catalysts,13b the coupling of 2-
phenylpyridine proceeded with low mono/di selectivity.
Furthermore, the arene substrate has been extended to a 2-
pyridone (7c) and a thiophene (7d). Diallylation products (7e
and 7f) were isolated in good to high yields when a pyrimidyl
directing group was used. In all cases, the reactions proceeded
smoothly under the standard or slightly modified conditions.
To briefly gain details of the reaction, 1a was subjected to the
present cobalt-catalyzed system in CD3COOD with or without
a 7-oxabenzonorbornadiene substrate (eqs 1 and 2). Significant
membered metallacyclic intermediate I. Coordination of the
bicyclic alkene to the Co center of I and subsequent insertion
into the CC bond generate intermediate II with a seven-
membered ring. Intermediate II undergoes β-oxygen elimi-
nation to give alkoxide intermediate III. Protonolysis of III
regenerates the active catalyst and releases the dihydronaphthol
intermediate, which is then dehydrated to give the product 3aa.
In conclusion, we have demonstrated cobalt(III)-catalyzed
C−C couplings of N-pyrimidinylindoles with strained rings
such as 7-oxabenzonorbornadienes and 2-vinyloxirane under
mild conditions. The coupling of 7-oxabenzonorbornadienes
resulted in 2-naphthylation of the N-pyrimidinylindoles, and
the coupling of 2-vinyloxirane yielded allylic alcohol products.
The reaction pathway likely involves the Co-catalyzed ortho C−
H activation, olefin insertion, and subsequent β-oxygen
elimination. The Co(III)-catalyzed coupling systems are
advantageous in terms of selectivity and efficiency. These
catalytic systems expand the synthetic utility of cobalt-catalyzed
C−H activation reactions. In view of the mild conditions, broad
scope, and high catalytic activity, this method may find
applications in the synthesis of complex structures.
levels of deuterium incorporation (10% and 37%, respectively)
at the 2-position of the recovered 1a were observed. In
addition, deuteration at the 3- and 7-positions was also
observed in both cases, indicating the reversibility of the C−
H bond cleavage. Moreover, a competition experiment between
1i and 1h was performed, and the more electron-deficient
indole reacted at a higher rate (eq 3), thus suggesting that the
C−H activation probably occurs via a concerted metalation−
deprotonation (CMD) mechanism.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01806.
■
S
Experimental details, characterization data, and copies of
NMR spectra of new compounds (PDF)
On the basis of previous reports,8a,13 a plausible mechanism
is proposed for the coupling of an indole with 7-
oxabenzonorbornadiene (Scheme 5). Initially, the cationic
Cp*Co(III) catalyst is generated with the assistance of AgSbF6.
Cyclometalation of the N-pyrimidinylindole affords five-
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: xwli@dicp.ac.cn.
C
DOI: 10.1021/acs.orglett.6b01806
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Zhang, W.; Liu, W.; Zhang, Y. Chem. Commun. 2016, 52, 6837.
(k) Yan, Q.; Chen, Z.; Liu, Z.; Zhang, Y. Org. Chem. Front. 2016, 3,
678. (l) Prakash, S.; Muralirajan, K.; Cheng, C.-H. Angew. Chem., Int.
Ed. 2016, 55, 1844.
(10) (a) Tsukada, N.; Sato, T.; Inoue, Y. Chem. Commun. 2001, 237.
(b) Ni, G.; Zhang, Q.-J.; Zheng, Z.-F.; Chen, R.-Y.; Yu, D.-Q. J. Nat.
Prod. 2009, 72, 966. (c) Matsubara, R.; Jamison, T. F. J. Am. Chem. Soc.
2010, 132, 6880.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge the financial support from the Dalian Institute
of Chemical Physics, Chinese Academy of Sciences, and the
National Natural Science Foundation of China (21525208 and
21272231). This work was also supored by the Strategic
Priority Research Program of the Chinese Academy of Sciences
(XDB17020300).
(11) Sundararaju, B.; Achard, M.; Bruneau, C. Chem. Soc. Rev. 2012,
41, 4467.
(12) For [Cp*Rh(III)]-catalyzed redox-neutral C−H allylation, see:
(a) Wang, H.; Schroder, N.; Glorius, F. Angew. Chem., Int. Ed. 2013,
̈
52, 5386. (b) Wang, H.; Beiring, B.; Yu, D.-G.; Collins, K. D.; Glorius,
F. Angew. Chem., Int. Ed. 2013, 52, 12430. (c) Feng, S.; Feng, D.; Loh,
T.-P. Chem. Commun. 2015, 51, 342. For [Cp*CoIII]-catalyzed redox-
neutral C−H allylation, see: (d) Yu, D.-G.; Gensch, T.; de Azambuja,
REFERENCES
■
(1) For selected reviews of transition-metal-catalyzed direct C−H
functionalization, see: (a) Chen, X.; Engle, K. M.; Wang, D. H.; Yu, J.-
Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (b) Colby, D. A.; Bergman,
R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (c) Cho, S. H.; Kim, J.
Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068. (d) Yeung, C.
S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (e) Song, G.; Wang, F.;
Li, X. Chem. Soc. Rev. 2012, 41, 3651. (f) Neufeldt, S. R.; Sanford, M.
S. Acc. Chem. Res. 2012, 45, 936. (g) Li, B.-J.; Shi, Z.-J. Chem. Soc. Rev.
2012, 41, 5588. (h) Bruckl, T.; Baxter, R. D.; Ishihara, Y.; Baran, P. S.
Acc. Chem. Res. 2012, 45, 826. (i) Hartwig, J. F. Acc. Chem. Res. 2012,
45, 864. (j) Kuhl, N.; Schroder, N.; Glorius, F. Adv. Synth. Catal. 2014,
356, 1443. (k) Ackermann, L. Acc. Chem. Res. 2014, 47, 281. (l) Chen,
Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Org. Chem. Front.
2015, 2, 1107. (m) Song, G.; Li, X. Acc. Chem. Res. 2015, 48, 1007.
(2) For recent reviews of Co(III)-catalyzed C−H bond functionaliza-
tion, see: (a) Yoshikai, N. ChemCatChem 2015, 7, 732. (b) Moselage,
M.; Li, J.; Ackermann, L. ACS Catal. 2016, 6, 498. (c) Wei, D.; Zhu,
X.; Niu, J.-L.; Song, M.-P. ChemCatChem 2016, 8, 1242.
́ ́
F.; Vasquez-Cespedes, S.; Glorius, F. J. Am. Chem. Soc. 2014, 136,
17722. (e) Suzuki, Y.; Sun, B.; Sakata, K.; Yoshino, T.; Matsunaga, S.;
Kanai, M. Angew. Chem., Int. Ed. 2015, 54, 9944. (f) Gensch, T.;
Vasquez-Cespedes, S.; Yu, D.-G.; Glorius, F. Org. Lett. 2015, 17, 3714.
́ ́
(g) Bunno, Y.; Murakami, N.; Suzuki, Y.; Kanai, M.; Yoshino, T.;
Matsunaga, S. Org. Lett. 2016, 18, 2216.
(13) (a) Qi, Z.; Li, X. Angew. Chem., Int. Ed. 2013, 52, 8995. (b) Yu,
S.; Li, X. Org. Lett. 2014, 16, 1200.
(14) Zell, D.; Bu, Q.; Feldt, M.; Ackermann, L. Angew. Chem., Int. Ed.
2016, 55, 7408.
̈
̈
(3) (a) Yoshino, T.; Ikemoto, H.; Matsunaga, S.; Kanai, M. Angew.
Chem., Int. Ed. 2013, 52, 2207. (b) Ikemoto, H.; Yoshino, T.; Sakata,
K.; Matsunaga, S.; Kanai, M. J. Am. Chem. Soc. 2014, 136, 5424.
(c) Sun, B.; Yoshino, T.; Matsunaga, S.; Kanai, M. Adv. Synth. Catal.
2014, 356, 1491. (d) Sun, B.; Yoshino, T.; Kanai, M.; Matsunaga, S.
Angew. Chem., Int. Ed. 2015, 54, 12968.
(4) (a) Zhao, D.; Kim, J. H.; Stegemann, L.; Strassert, C. A.; Glorius,
F. Angew. Chem., Int. Ed. 2015, 54, 4508. (b) Lerchen, A.; Vasquez-
Cespedes, S.; Glorius, F. Angew. Chem., Int. Ed. 2016, 55, 3208.
(5) (a) Li, J.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 8551.
(b) Li, J.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 3635.
(c) Wang, H.; Koeller, J.; Liu, W.; Ackermann, L. Chem. - Eur. J. 2015,
21, 15525. (d) Ma, W.; Ackermann, L. ACS Catal. 2015, 5, 2822.
(e) Wang, H.; Moselage, M.; Gonzalez, M. J.; Ackermann, L. ACS
Catal. 2016, 6, 2705.
(6) (a) Hummel, J. R.; Ellman, J. A. J. Am. Chem. Soc. 2015, 137, 490.
(b) Hummel, J. R.; Ellman, J. A. Org. Lett. 2015, 17, 2400. (c) Boerth,
J. A.; Hummel, J. R.; Ellman, J. A. Angew. Chem., Int. Ed. 2016,
DOI: 10.1002/anie.201603831.
(7) (a) Grigorjeva, L.; Daugulis, O. Angew. Chem., Int. Ed. 2014, 53,
10209. (b) Grigorjeva, L.; Daugulis, O. Org. Lett. 2015, 17, 1204.
(c) Nguyen, T. T.; Grigorjeva, L.; Daugulis, O. ACS Catal. 2016, 6,
551.
(8) (a) Park, J.; Chang, S. Angew. Chem., Int. Ed. 2015, 54, 14103.
(b) Pawar, A. B.; Chang, S. Org. Lett. 2015, 17, 660. (c) Patel, P.;
Chang, S. ACS Catal. 2015, 5, 853.
(9) (a) Zhang, Z.-Z.; Liu, B.; Wang, C.-Y.; Shi, B.-F. Org. Lett. 2015,
17, 4094. (b) Zhang, Z.-Z.; Liu, B.; Xu, J.-W.; Yan, S.-Y.; Shi, B.-F. Org.
Lett. 2016, 18, 1776. (c) Kong, L.; Yu, S.; Zhou, X.; Li, X. Org. Lett.
2016, 18, 588. (d) Wang, F.; Wang, H.; Wang, Q.; Yu, S.; Li, X. Org.
Lett. 2016, 18, 1306. (e) Kong, L.; Yang, X.; Zhou, X.; Yu, S.; Li, X.
Org. Chem. Front. 2016, 3, 813. (f) Liu, X.-G.; Zhang, S.-S.; Jiang, C.-
Y.; Wu, J.-Q.; Li, Q.; Wang, H. Org. Lett. 2015, 17, 5404. (g) Zhang,
S.-S.; Liu, X.-G.; Chen, S.-Y.; Tan, D.-H.; Jiang, C.-Y.; Wu, J.-Q.; Li,
Q.; Wang, H. Adv. Synth. Catal. 2016, 358, 1705. (h) Liang, Y.; Liang,
Y.-F.; Tang, C.; Yuan, Y.; Jiao, N. Chem. - Eur. J. 2015, 21, 16395.
(i) Liang, Y.; Jiao, N. Angew. Chem., Int. Ed. 2016, 55, 4035. (j) Yu, W.;
D
DOI: 10.1021/acs.orglett.6b01806
Org. Lett. XXXX, XXX, XXX−XXX