Cobalt-catalyzed intramolecular decarbonylative coupling of acylindoles and diarylketones through the cleavage of C-C bonds

Article abstract of DOI:10.1039/d0sc04326e

We report here cobalt-N-heterocyclic carbene catalytic systems for the intramolecular decarbonylative coupling through the chelation-assisted C-C bond cleavage of acylindoles and diarylketones. The reaction tolerates a wide range of functional groups such as alkyl, aryl, and heteroaryl groups, giving the decarbonylative products in moderate to excellent yields. This transformation involves the cleavage of two C-C bonds and formation of a new C-C bond without the use of noble metals, thus reinforcing the potential application of decarbonylation as an effective tool for C-C bond formation. This journal is

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DOI: 10.1039/D0SC04326E
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Cobalt-Catalyzed Intramolecular Decarbonylative Coupling of
Acylindoles and Diarylketones through the Cleavage of C−C Bonds
Received 00th January 20xx,
Accepted 00th January 20xx
Tian-Yang Yu, ‡ Wen-Hua Xu, ‡ Hong Lu and Hao Wei *
DOI: 10.1039/x0xx00000x
We report here cobalt−N-heterocyclic carbene catalytic systems for the intramolecular decarbonylative coupling through
the chelation-assisted C−C bond cleavage of acylindoles and diarylketones. The reaction tolerates a wide range of
functional groups such as alkyl, aryl, and heteroaryl groups, giving the decarbonylative products in moderate to excellent
yields. This transformation involves the cleavage of two C−C bonds and formation of new C−C bond without the use of
noble metals, thus reinforcing the potential application of decarbonylation as an effective tool for C−C bond formation.
that nickel enables the decarbonylation of ketones.5 In recent
years, cobalt has received considerable attention in the
activation of strong σ-bonds owing to its low price, ability to
Introduction
Catalytic decarbonylation has attracted considerable attention
in organic synthesis.1 In particular, intramolecular
decarbonylative coupling emerged as a more efficient and
higher atom-economic strategy for the efficient formation of
chemical bonds. This method allows for a common carbonyl
group to serve as a “traceless handle” for chemical bond
formation. In the past few decades, advances in intramolecular
decarbonylative coupling, which can be used to create C−C,
C−P, C−N, C−O, C−S and C−Si bonds through transition-metal
catalysis, have been made (Scheme 1A).2
access multiple oxidation states, and its extensive, yet reactive,
organometallic chemistry.6 Co carbonyl complexes are also
known to catalyze several carbonylative processes (Scheme
1B).7 Decarbonylation involves C(=O)−C bond oxidative
addition, CO extrusion, and C−C bond forming reductive
elimination, which can be regarded as the reverse process of
carbonylation (Scheme 1C). The excellent affinity of Co with a
carbonyl group inspired us to explore the use of this metal as
the catalyst for decarbonylation. To our knowledge, Co-
catalyzed decarbonylation is challenging and remains unsolved
Synthesis of bi(hetero)aryls very common in the
pharmaceutical, agrochemical, and materials industries.3 From
the view point of step and atom economy, transition-metal-
catalyzed intramolecular decarbonylative coupling of ketones
8
so far.
Herein, we disclose the first Co-catalyzed
decarbonylation of ketones with the assistance of an N-
containing directing group,9 in which an intramolecular
decarbonylative coupling of acylindoles and diarylketones was
realized with an inexpensive cobalt precatalyst.
would offer
a distinct strategy for the synthesis of
bi(hetero)aryls, which has presented many attractive features.
For example, ketones can be readily prepared, are stable, and
generally have low toxicity. In addition, the use of this strategy
helps to reduce the amount of harmful waste products (CO is
the major side product). Finally, this reaction allows carbonyl
of ketones to become a “traceless handle” for the construction
C−C bond, which will improve the flexibility of synthetic
design.1c,1k Although highly attractive, the typical use of
expensive and noble Rh complexes may hinder the
development of this field.4 First row transition metals (iron,
cobalt, nickel, and copper) are typically inexpensive and earth-
abundant; the replacement of second row transition metals as
catalysts with first row transition metals would be
revolutionary. Pioneering work in this field has demonstrated
A. Intramolecular decarbonylative couplings
O
M catalyst
R
X
R
X
X = C, O, N, P, S, Si
M = Rh, Pd and Ni
B. The process of Co-catalyzed carbonylation
R2
O
CO
R1 [Co]
R1 [Co] R2
CO insertion
C. The process of Co-catalyzed decarbonylation: This work
DG
DG
R
R
O
(Het)Ar
(Het)Ar
[Co]
oxidative
addition
reductive
elimination
DG
DG
R
O
Key Laboratory of Synthetic and Natural Functional Molecule of Ministry of the
Education, College of Chemistry & Materials Science, Northwest University, Xi’an
710069, China. E-mail:haow@nwu.edu.cn
Electronic Supplementary Information (ESI) available: synthetic procedures and
experimental details. CCDC 1965066. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/x0xx00000x
[Co]
R
[Co]
(Het)Ar
(Het)Ar
CO extrusion
CO
Scheme 1. Inspiration for Co-catalyzed decarbonylation.
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Journal Name
Results and discussion
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Ph
Ph
O
Ph
O
Ph
DOI: 10.1039/D0SC04326E
N
N
N
H
N
O
N
O
Table 1 Evaluation of reaction conditionsa
O
NMe2
Ph
1a-3, No reaction
O
1a-1, 74%
Co2(CO)8 (10 mol%)
1a-2, No reaction
1a-4, No reaction
IMes•HCl (20 mol%)
Cs2CO3 (40 mol%)
Ph
Ph
+
Scheme 2 Screening of directing groups.
H
N
pym
2a
dioxane, 150 o
36 h
C
N
N
pym
1a
O
pym
2a-H
With the optimized reaction conditions in hand, we next
investigated the scope of indole substrates. As shown in Table
2, electron-donating and -withdrawing substituents at the 3-,
4-, 5-, and 6-positions were compatible with the reaction
conditions. Common functional groups such as aryl fluoride
(2b), cyanide (2c), acetyl (2d), ether (2e and 2f),
trifluoromethyl (2h) and ester (2i) were unaffected by the
reaction conditions, thus highlighting the versatility of the
transformation. The reaction efficiency was unaffected when a
3-methyl group (2k) was introduced, thus indicating tolerance
of steric hindrance. A wide variety of electron-donating (2r) or
electron-withdrawing (2m, 2s and 2t) substituents on the
benzene ring were also well tolerated. Polyaromatic ketones
(2u and 2v) reacted smoothly to give the corresponding
decarbonylation products. The substrates could be changed
from indole to pyrrole, with pyrimidine as a directing group, to
furnish the desired product 2x in moderate yield. In addition,
aryl alkyl ketones were suitable for this transformation, and
the corresponding 2-alkyl indoles (2ya-2yf) were obtained in
moderate yields.10 Note that aryl alkyl ketones had failed in
the Ni system. However, under the standard conditions, no
products were detected when secondary alkyl aryl ketones
were used (2yg, 2yh and 2yi), affording byproduct 2a-H.
Yield b [%]
2a
93
0
18
85
68
14
47
72
80
86
0
Entry
Deviations from above
2a-H
<5
0
1
2
3
4
5
6
7
8
9
10
11
12
13
“standard conditions” with 1a
without Co2(CO)8
without IMes·HCl
IMes·HCl (10 mol%)
0
<5
10
17
20
<5
<5
<5
70
10
19
ICy·HCl instead of IMes·HCl
SIPr·HCl instead of IMes·HCl
IPr·HCl instead of IMes·HCl
P(n-Bu)3 instead of IMes·HCl
PCy3 instead of IMes·HCl
toluene instead of dioxane
iPrOH instead of dioxane
CoBr2 instead of Co2(CO)8
salenCo(II) instead of Co2(CO)8
0
0
N
N
N
N
R
R
R
R
SIPr (R = 2,6-iPr2C6H3)
IMes (R = 2,4,6-Me3C6H2)
ICy (R = cyclohexyl)
IPr (R = 2,6-iPr2C6H3)
a
Standard conditions: 1a (0.1 mmol), Co2(CO)8 (10 mol%), IMes·HCl (20 mol%),
Cs2CO3 (40 mol%), dioxane (0.5 mL) at 150 °C in sealed tube, 36 h. Isolated
yields.
b
We also investigated the decarbonylation of diaryl ketones.
For these substrates, ICy instead of IMes in the Co catalysis
gave better yields (see Supporting Information). A variety of
N-pyrimidinyl 2-benzoyl indole 1a was employed as the
model substrate. After a careful survey of the reaction
parameters (see Supporting Information), we discovered that
the combined use of Co2(CO)8, IMes·HCl, and Cs2CO3 in dioxane
afforded 2-phenyl indole 2a in 93% yield (Table 1, entry 1).
Control experiments were carried out to understand the role
of each reactant (see Table 1). In the absence of Co2(CO)8, the
desired product was not observed (entry 2). The reaction
without the ligand afforded the desired product, albeit in a
lower yield (entry 3). When IMes·HCl (20 mol%) loading was
reduced to IMes·HCl (10 mol%), the reaction proceeded 85%
yield of 2a (entry 4). Other NHC ligands also promoted this
reaction but gave lower yields as compared to that obtanied
with IMes (entries 5-7). Phosphine ligands such as P(n-Bu)3 or
PCy3 also promoted this reaction but the yields were lower
(entries 8 and 9). Dioxane as the solvent proved to be superior
diaryl ketones bearing
a 2-pyridyl directing group also
underwent decarbonylation to deliver the corresponding
products in moderate to good yields. Further, a wide variety of
functional groups, including ethers, trifluoromethyl, fluorides,
and esters, were tolerated in the reaction. The directing group
was also extended to a pyrimidine (4m) and a pyrazole (4o),
however, no product was observed when directing group was
replaced with an oxime (4p).
A preliminary density functional theory (DFT) study was
conducted to explore the reaction mechanism (Figure 1). The
geometries were optimized at the B3LYP/DZ level of theory 11
and the electronic energies were further improved by single-
point calculations at the M06/TZ level.12 Solvation effects in
1,4-dioxane were treated by the continuum implicit solvation
model SMD.13a In the simulation, we chose Co2(CO)4(NHC) to
be the catalyst as can be seen from Figure 2 (The justifications
are described in the Supporting Information). The dissociation
of CO ligands is necessary to initiate catalysis and create
coordination sites (Co2(CO)8 + L = Co2(CO)4L (CAT) + 4CO (ΔG =
25.2 kcal mol-1). The catalytic cycle commences upon
coordination between the Co(0) complex (CAT) and substrate
1a, giving the catalyst-substrate complex INT1.
i
to toluene or PrOH (entries 10 and 11). Co(II) complexes such
as CoBr2 and salen Co complexes were not reactive for this
transformation(entries 12 and 13). Next, several other
coordinating groups were tested (Scheme 2). Comparable
results were obtained when replacing the pyrimidyl group with
a pyridyl group (1a-1), while no product was observed when
the pyrimidyl group was removed (1a-2) or replaced with a
weakly coordinating group such as urea or carboxamide (1a-3
and 1a-4).
2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0SC04326E
ARTICLE
Table 2 Intramolecular carbonylative coupling of ketonesa
Co2(CO)8 (10 mol%)
IMes•HCl (20 mol%)
Cs2CO3 (40 mol%)
DG
DG
R
R
O
(Het)Ar
(Het)Ar
dioxane, 150 o
36 h
C
Indolyl Ketones
Me
NC
MeOC
MeO
Ph
BnO
F
Ph
Ph
pym
Ph
Ph
pym
Ph
Ph
N
pym
Ph
N
N
N
N
N
N
N
F3C
pym
pym
pym
pym
pym
2a,
2b,
2c,
2d,
2e,
2f,
2g,
76%
2h,
93%
90%
83%
Me
81%
85%
87%
85%
F
Ph
Ph
Ph
Me
Et
N
pym
N
pym
N
pym
N
pym
N
pym
N
pym
N
pym
MeOOC
MeO
Me
2i,
2j,
2k,
2l,
2m,
2n,
91%
82%
83%
87%
89%
48%
2o,
82%
tBu
Ph
OMe
CN
CF3
N
N
N
N
N
N
N
pym
pym
pym
pym
pym
pym
pym
2p,
2q,
2r,
2s,
2t,
2u,
2v,
83%
87%
88%
68%
70%
93%
90%
Me
Ph
Et
Ph
Ph
Ph
N
O
N
pym
2x,
N
pym
N
pym
N
pym
N
pym
Me
pym
2w,
b
b
b
2yd
90%
51%
X-ray of
2ya,
2yb,
2yc
2yd,
52%
57%
, 61%
52%b
Ph
OMe
iPr
pym
2yh,
tBu
0%
N
pym
N
pym
N
pym
N
N
pym
b
b
2ye
2yf
2yg
2yi,
, 42%
, 60%
, 0%
0%
Diaryl Ketones
N
N
Me
N
Et
N
Ph
N
OMe
N
OBn
N
CF3
N
F
4a, 90%c
4c, 80%c
4d, 82%c
4b, 90%c
4e, 91%c
4f, 90%c
4g, 47%c
4h, 60%c
OMe
N
CO2Me
N
N
Me
N
N
N
N
N
N
N
O
S
c
c
c
4i, 51%c
4j, 85%c
4k, 81%c
4l, 60%c
4p,
0%
4m
4n,
4o,
72%
, 85%
92%
a Reaction conditions: 1 (0.1 mmol), Co2(CO)8 (0.01 mmol, 10 mol%), IMes·HCl (0.02 mmol, 20 mol%), Cs2CO3 (0.04 mmol, 40 mol%), dioxane (0.5 mL) at 150
°C, 36 h in sealed tube, isolated yields. b PCy3 as ligand and toluene as solvent. c ICy as ligand.
Then, INT1 undergoes oxidative addition to form INT2A via INT3A or INT3B was also considered but deemed unlikely as
TS1, requiring an activation free energy of 18.9 kcal mol−1; this the energy barrier (TS4) is 2 kcal/mol higher than that of TS3.
step is endergonic by 12.3 kcal mol−1. INT2A is converted to The overall free energy for the reaction is -3.1 kcal mol-1.
INT2B via the transfer of carbon monoxide. Next, INT2B is Considering the activation free energy of each step, evidently,
converted to INT3A via decarbonylation, requiring an the highest energy barrier is the transition from INT1 to TS1
activation free energy of 8.5 kcal mol−1. The decarbonylation (18.9 kcal mol-1). According to the energetic span
step was endergonic by 4.1 kcal mol−1. INT3A can rearrange approximation,13b,13c the rate-determining transition state
into intermediate INT3B, which then undergoes reductive (RDTS) and the rate-determining intermediate (RDI) are TS3
elimination to form INT4 (via TS3). Finally, INT4 is converted to and INT1, respectively, thus, the energetic span δE = 25.2 kcal
INT5 with the release of CO.14 The dissociation of CO from mol-1.
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DOI: 10.1039/D0SC04326E
L
Co(CO)3
CO
CO
Co
N
TS4
17.0
TS3
TS4
N
N
TS2
TS3
15.0
O
TS2
14.0
INT3A
INT3A
CO
N
Co
Co(CO)2
L
N
N
O
CO
INT3A'
8.6
9.6
TS1
8.7
N
INT2A
CO
Co
INT2B
5.5
O
INT3B'
5.3
N
O
N
L
Co(CO)2
CO
Co
O
L
N
N
Co
INT2A
2.1
CAT+
1a
CO
TS1
INT5
N
CAT+
2a
-3.1
0.0
INT5
-3.0
CO
INT3A'
O
INT3B
0.4
O
CO
N
Co
L
L
Co(CO)2
Co(CO)3
CO
Co
N
Co(CO)3
L
N
N
N
Co
L
Co(CO)2
O
CO
N
N
O
N
CO
N
CO
CO
N
N
N
Co
N
INT2B
O
N
Co
N
CO
INT1
-10.2
Co
O
L
CO
INT4
INT3B
INT4
-10.6
INT3B'
CO
INT1
Decarbonylation
Reductive elimination
Oxidative addition
Figure 1 Density functional theory (DFT) calculated pathways for the intramolecular decarbonylative coupling
Finally, the utility of this reaction was demonstrated for a
A. Synthesis of Benzo[a]carbazole
variety of valuable target motifs (Scheme 3A). The N-pyrimidyl
directing group could be smoothly removed from 2a to obtain
the corresponding N–H indole 5a in 82% yield. In the presence
of IBr, 5a reacted with acetophenone to give the
corresponding carbazole derivative 6a.15 Such scaffolds are
prevalent in natural products and drug candidates with
intriguing bioactivities,16 thus highlighting the synthetic
applicability of the present method. The protocol was
additionally applied to the synthesis of bazedoxifene, a third-
generation selective estrogen receptor modulator (SERM).17 As
shown in Scheme 3B, the synthesis was initiated by the
conversion of ketones 7 to 8 under standard conditions.
Removal of the directing group from 8 gave indole derivative 9.
The conversion of 9 to bazedoxifene has been reported.17c
NaOEt
EtOH/DMSO
100 oC, 20 h
(82%)
IBr
Ph
Ph
N
O
N
H
pym
2a
5a
Ph
Me
Ph
N
H
6a, 70%
Benzo[ ]carbazole
a
B. Synthesis of Bazedoxifene
OBn
Co2(CO)8 (10 mol%)
IMes•HCl (20 mol%)
Cs2CO3 (40 mol%)
Me
Me
BnO
BnO
OBn
dioxane, 150 oC,
N
pym
N
pym
7
O
36 h
(89%)
8
Me
BnO
two steps
NaOEt, DMSO
100 oC, 20 h
(85 %)
OBn
N
H
9
Me
N
HO
OH
Conclusions
N
O
In summary, we have discovered a simple Co system that
can catalyze the decarbonylation of ketones via the cleavage
of two C−C bonds. This work showcases the unique ability of
the Co catalyst to trigger C−C bond disconnections, and further
reinforces the potential of using decarbonylation as a tool for
chemical bond formation and cleavage. However this coupling
reaction is still associated with significant drawbacks such as
the requirement of high temperatures and directing group.The
use of directing groups aids the decarbonylation, but it
complicates the whole synthesis and limits the application of
this strategy in synthesis.18 Studies aimed at expanding this
decarbonylative strategy to simple ketones without directing
group are ongoing in our laboratories.
Bazedoxifene (11)
Scheme 3 Synthetic utility.
Conflicts of interest
There are no conflicts to declare
Acknowledgements
Financial support for this work was provided by the National
Natural Science Foundation of China (NSFC 21901202 and
21971205) and Natural Science Basic Research Program of
Shaanxi (2020JQ-576). We thank the chemical HPC center of
NWU for computational resources. Dedicated to Professor
Peng-Fei Xu on the occasion of his 56th birthday.
4 | J. Name., 2012, 00, 1-3
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7
8
(a) Q. Liu, H. Zhang and A. Lei, Angew. Chem. IVnietw. EArdti.c,le2O0n1lin1e,
Notes and references
50, 10788–10799; (b) Y. Li, Y. Hu and X.-F. Wu, Chem. Soc.
DOI: 10.1039/D0SC04326E
1
For recent reviews and highlights, see: (a) A. Dermenci and G.
Dong, Sci. China Chem., 2013, 56, 685–701; (b) F. Chen, T.
Wang and N. Jiao, Chem. Rev., 2014, 114, 8613–8661; (c) A.
Dermenci, J. W. Coe and G. Dong, Org. Chem. Front., 2014, 1,
567–581; (d) L. Souillart and N. Cramer, Chem. Rev., 2015,
115, 9410–9464; (e) Y.-F. Liang and N. Jiao, Acc. Chem. Res.,
2017, 50, 1640–1653; (f) G. Fumagalli, S. Stanton and J. F.
Bower, Chem. Rev., 2017, 117, 9404–9432; (g) R. Takise, K.
Muto and J. Yamaguchi, Chem. Soc. Rev., 2017, 46, 5864–
5888; (h) R. J. Somerville and R. Martin, Angew. Chem. Int.
Ed., 2017, 56, 6708–6710; (i) C. Liu and M. Szostak, Org.
Biomol. Chem., 2018, 16, 7998–8010; (j) L. Guo and M.
Rueping, Chem. Eur. J., 2018, 24, 7794–7809; (k) Q. Zhao and
M. Szostak, ChemSusChem 2019, 12, 2983–2987; (l) H. Lu, T.-
Y. Yu, P.-F. Xu and H. Wei, Chem Rev., 2020, DOI:
10.1021/acs.chemrev.0c00153.
Rev., 2018, 47, 172–194.
(a) L. F. Halle, W. E. Crowe, P. B. Armentrout and J. L.
Beauchamp, Organometallics, 1984, 3, 1694–1706; (b) Z. Zhu,
X. Li, S. Chen, P. Chen, B. A. Billett, Z. Huang and G. Dong,
ACS Catal., 2018, 8, 845–849; (c) X.-T. Min, D.-W. Ji, H. Zheng,
B.-Z. Chen, Y.-C. Hu, B, Wan and Q.-A Chen, Org. Lett., 2020,
22, 3386−3391.
9
(a) N. Chatani, Y. Ie, F. Kakiuchi and S. Murai, J. Am. Chem.
Soc., 1999, 121, 8645−8646; (b) R. Zeng and G. Dong, J. Am.
Chem. Soc., 2015, 137, 1408–1411; (c) Z.-Q. Lei, F. Pan, H. Li,
Y. Li, X.-S. Zhang, K. Chen, X. Wang, Y.-X. Li, J. Sun and Z.-J.
Shi, J. Am. Chem. Soc., 2015, 137, 5012−5020; (d) Y. Hibe, Y.
Ebe, T. Nishimura and H. Yorimitsu, Chem. Lett., 2017, 46,
953–955; (e) Lyori, Y.; Takahashi, K.; Yamazaki, K.; Ano, Y.;
Chatani, N. Chem. Commun., 2019, 55, 13610–13613.
10 See the Supporting Information for details (Table S9).
11 (a) P. C. Hariharan and J. A. Pople, Theor. Chim. Acta., 1973,
28, 213–222; (b) P. Jeffrey Hay and W. R. Wadt, J. Chem.
Phys., 1985, 82, 270–283; (c) A. D. Becke, Phys. Rev. A At Mol.
Opt. Phys., 1988, 38, 3098–3100; (d) C. Lee, W. Yang and R. G.
Parr, Phys. Rev. B: Condens Matter Mater Phys., 1988, 37,
785–789; (e) A. D. Becke, J. Chem. Phys., 1993, 98, 5648–
5652.
12 (a) A. D. McLean and G. S. Chandler. J. Chem. Phys., 1980, 72,
5639–5648; (b) A. W. Ehlers, M. Böhme , S. Dapprich, A.
Gobbi, A. Höllwarth, V. JonaS, K. F. Köhler, R. Stegmann, A.
Veldkamp and G. Frenking, Chem. Phys. Lett., 1993, 208,
111–114; (c) L. E. Roy, P. Jeffrey Hay and R. L. Martin. J.
Chem. Theory. Comput., 2008, 4, 1029–1031; (d) Y. Zhao and
D. Truhlar, Theor. Chem. Acc., 2008, 120, 215–241.
13 (a) A. V. Marenich, C. J. Cramer and D. G. Truhlar. J. Phys.
Chem. B., 2009, 113, 6378–6396; (b) S. Kozuch and S. Shaik,
Acc. Chem. Res., 2011, 44, 101–110; (c) S. Kozuch and J. M. L.
Martin, ChemPhysChem., 2011, 12, 1413–1418.
14 (a) M. A. Ortuñ, B. Dereli and C. J. Cramer. Inorg. Chem.,
2016, 55, 4124–4131; (b) S. H. H. Eliasson and V. R. Jensen.
Faraday Discuss., 2019, 220, 231–248.
15 P. Ni, J. Tan, W. Zhao, H. Huang, F. Xiao, G. J. Deng, Org. Lett.,
2019, 21, 3687–3691.
16 (a) H.-J. Knölker and K. R. Reddy, Chem. Rev., 2002, 102,
4303–4428; (b) H.-J. Knölker, Top. Curr. Chem., 2005, 244,
115–148; (c) I. Bauer and H.-J. Knölker. Top. Curr. Chem.,
2011, 309, 203–253; (d) H. Jiang, J. Sun and J. Zhang, Curr.
Org. Chem., 2012, 16, 2014–2025.
17 (a) C. P. Miller, H. A. Harris and B. S. Komm, Drugs Future,
2002, 27, 117–121; (b) B. S. Komm, Y. P. Kharode, P. V. N.
Bodine, H. A. Harris, C. P. Miller and C. R. Lyttle,
Endocrinology, 2005, 146, 3999–4008; (c) S. Chen, X. K. Liu, X.
Yu and Z. D. Yuan, Chinese Journal of New Drugs, 2013, 13,
1571–1573.
18 (a) J. Li and L. Ackermann, Chem. Eur. J., 2015, 21,
5718−5722; (b) D. Zell, M. Bursch, V. Müller, S. Grimme and L.
Ackermann, Angew. Chem. Int. Ed., 2017, 57, 10378–10382.
2
For selected recent examples for intramolecular
decarbonylative coupling: (a) M. Murakami, H. Amii and Y.
Ito, Nature, 1994, 370, 540–541; (b) T. Kondo, A. Nakamura,
T. Okada, N. Suzuki, K. Wada and T. A. Mitsudo, J. Am. Chem.
Soc., 2000, 122, 6319–6320; (c) T. Kondo, Y. Taguchi, Y.
Kaneko, M. Niimi and T. A. Mitsudo, Angew. Chem. Int. Ed.,
2004, 43, 5369–5372; (d) T. Matsuda, M. Shigeno and M.
Murakami, Chem. Lett., 2006, 35, 288–289; (e) A. Dermenci,
R. E.Whittaker and G. Dong, Org. Lett., 2013, 15, 2242–2245;
(f) A. Dermenci, R. E. Whittaker, Y. Gao, F. Cruz, Z. Yu and G.
Dong, Chem. Sci., 2015, 6, 3201−3210; (g) R. E. Whittaker
and G. Dong, Org. Lett., 2015, 17, 5504−5507; (h) R. Yu, X.
Chen, S. F. Martin and Z. Wang, Org. Lett., 2017, 19, 1808–
1811; (i) X. Liu, H. Yue, J. Jia, L. Guo and M. Rueping, Chem.
Eur. J., 2017, 23, 11771–11775; (j) R. Takise, R. Isshiki, K.
Muto, I. Kenichiro and J. Yamaguchi, J. Am. Chem. Soc., 2017,
139, 3340–3343; (k) N. Ichiishi, C. A. Malapit, Ł. Woźniak and
M. S. Sanford, Org. Lett., 2018, 20, 44–47; (l) C. Liu and M.
Szostak, Chem. Commun., 2018, 54, 2130–2133; (m) K.
Ishitobi, R. Isshiki, K. K. Asahara, C. Lim, K. Muto and J.
Yamaguchi, Chem. Lett., 2018. 47, 756–759; (n) Z.-J. Zheng, C.
Jiang, P.-C. Shao, W.-F. Liu, T.-T. Zhao, P.-F. Xu and H. Wei,
Chem. Commun., 2019, 55, 1907–1910; (o) T. Morioka, S.
Nakatani, T. Sakamato, T. Kodama, S. Ogoshi, N. Chatani and
M. Tobisu, Chem. Sci., 2019, 10, 6666–6671; (p) W.
Srimontree, W. Lakornwong and M. Rueping, Org. Lett., 2019,
21, 9330–9333; (q) C. E. Brigham, C. A. Malapit, N. Lalloo and
M.
S.
Sanford,
ACS
Catal.,
2020,
DOI:
10.1021/acscatal.0c02950.
3
(a) J. Magano and J. R. Dunetz, Chem. Rev., 2011, 111,
2177−2250; (b) C. A. Busacca, D. R. Fandrick, J. J. Song and C.
H. Senanayake, Adv. Synth. Catal., 2011, 353, 1825−1864; (c)
S. D. Roughley and A. M. Jordan, J. Med. Chem., 2011, 54,
3451−3479.
4
5
6
(a) O. Daugulis and M. Brookhart, Organometallics, 2004, 23,
527−534; (b) Z.-Q. Lei, H. Li, Y. Li, X.-S. Zhang, K. Chen, X.
Wang, J. Sun and Z.-J. Shi, Angew. Chem. Int. Ed., 2012, 51,
2690–2694.
(a) T. Morioka, A. Nishizawa, T. Furukawa, M. Tobisu and N.
Chatani, J. Am. Chem. Soc., 2017, 139, 1416−1419; (b) T.-T.
Zhao, W.-H. Xu, Z.-J. Zheng, P.-F. Xu and H. Wei, J. Am. Chem.
Soc., 2018, 140, 586−589.
(a) W. Song and L. Ackermann, Angew. Chem., Int. Ed., 2012,
51, 8251−8254; (b) D.-G. Yu, X. Wang, R. Zhu, S. Luo, X.-B.
Zhang, B.-Q. Wang, L. Wang and Z.-J. Shi. J. Am. Chem.
Soc., 2012, 134, 14638–14641; (c) B. Su, Z.-C. Cao and Z.-J.
Shi, Acc. Chem. Res., 2015, 48, 886–896; (d) M. Moselage, J.
Li and L. Ackermann, ACS Catal., 2016, 6, 498–525; (e) F. H.
Lutter, L. Grokenberger, M. S. Hofmayer and P. Knochel,
Chem. Sci., 2019, 10, 8241–8245.
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Chemical Science
Page 6 of 6
View Article Online
DOI: 10.1039/D0SC04326E
DG
R
DG
O
Co
R
Co
(Het)Ar
(Het)Ar
Cobalt
 earth-abundant cobalt
 cleavage of two C-C bonds
 high reaction yields
A method for cobalt−N-heterocyclic carbene catalytic systems for the intramolecular
decarbonylative coupling of ketones was achived