Rhodium-catalyzed decarbonylation cross-coupling reactions of aromatic aldehydes and arylboronic acids via C–C bond activation directed by a guide group chelation

Article abstract of DOI:10.1016/j.inoche.2020.108065

A rhodium-catalyzed decarbonylative cross-coupling reaction of benzoquinoline-10-carbaldehydes with arylboronic acids through chelation-assisted sp² C–CHO bond activation has been developed. A variety of functional groups substituted phenylboronic acids or benzoquinoline-10-carbaldehydes are compatible with the reaction under the optimized reaction conditions, the corresponding 10-phenylbenzo[h]quinoline derivatives were obtained in moderate to good yields. The method affords a useful strategy for the synthesis of N-heterocyclic biaryl compounds via rhodium-catalyzed sp² C–CHO bond activation.

Full text of DOI:10.1016/j.inoche.2020.108065

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Short communication
Rhodium-Catalyzed Decarbonylation Cross-coupling Reactions of Aromatic
Aldehydes and Arylboronic Acids via C-C Bond Activation Directed by a
Guide Group Chelation
Xiaobo Yu, Guanchen Liu, Shudong Geng
PII:
S1387-7003(20)30655-9
DOI:
https://doi.org/10.1016/j.inoche.2020.108065
INOCHE 108065
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Inorganic Chemistry Communications
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Revised Date:
Accepted Date:
4 April 2020
21 June 2020
22 June 2020
Please cite this article as: X. Yu, G. Liu, S. Geng, Rhodium-Catalyzed Decarbonylation Cross-coupling Reactions
of Aromatic Aldehydes and Arylboronic Acids via C-C Bond Activation Directed by a Guide Group Chelation,
Inorganic Chemistry Communications (2020), doi: https://doi.org/10.1016/j.inoche.2020.108065
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Rhodium-Catalyzed Decarbonylation Cross-coupling Reactions of
Aromatic Aldehydes and Arylboronic Acids via C-C Bond Activation
Directed by a Guide Group Chelation
Xiaobo Yu *, Guanchen Liu, Shudong Geng
College of Materials Science and Engineering, Jilin Institute of Chemical Technology, Jilin City
132022, P. R.China.
ABSTRACT: A rhodium-catalyzed decarbonylative cross-coupling reaction of
benzoquinoline-10-carbaldehydes with arylboronic acids through chelation-assisted sp2
C−CHO bond activation has been developed. A variety of functional groups substituted
phenylboronic acids or benzoquinoline-10-carbaldehydes are compatible with the
reaction under the optimized reaction conditions, the corresponding 10-
phenylbenzo[h]quinoline derivatives were obtained in moderate to good yields. The
method affords a useful strategy for the synthesis of N-heterocyclic biaryl compounds
via rhodium-catalyzed sp2 C-CHO bond activation.
Keywords: Rhodium-catalyzed; Decarbonylation; Cross-coupling; C-C bond
activation; Benzoquinoline-10-carbaldehyde
1. Introduction
Transition metal catalyzed C-C bond activation reaction can rapidly and efficiently
synthesize organic compounds through reorganizing existing molecular skeletons,
[1,2]
which has attracted much attention in recent decades.
The field is also facing
challenges because of the thermodynamic and kinetic inertia of C-C bonds.
The C-C bond activation reactions usually are achieved through various activation
strategies. One of the successful strategies for non-tensioned ring molecules is the use
of directing groups, which introduce the transition metal catalyst into the immediate
vicinity of the desired activation site via a directing group to overcome the intrinsic
stability of the C-C bond. [1]
Quinolinones are good metal-directing agents that have been earlier used for
directing group activation strategies.[3] The initial reactions were mainly intramolecular
C-C bond activation reactions of quinolinones. Later, Wang's group reported that the
reaction of direct exchange of groups between quinolinones and arylboronic acids via
C-C bond activation reaction.[4] Johnson reported that rhodium-catalyzed
interconversion of quinolinyl ketones with boronic acids via C−C bond activation [2a]
.
Compared with quinolinones, benzoquinoline is also a good metal-directing
reagent, and is widely used for C-H bond activation reactions.[5] Benzoquinoline
derivatives are also used in some C-C bond activation reactions. Wang's group reported
that rhodium-catalyzed C-C bond activation coupling reaction of benzoquinolin-10-
ethyl esters with arylboronic acids. [6]
Based on this research, we further reported that another rhodium-catalyzed C-C

bond activation of benzoquinolin-10-methanols and arylboronic acids to afford biaryl
[7]
compounds.
The reaction mechanism suggests that the oxidation of the primary
alcohol to an aldehyde may be the key step in this cross-coupling reaction. This
prompted us to study the C-C bond activation reaction of benzoquinoline-10-
carboxaldehyde.
On the other hand, transition-metal-catalyzed decarbonylation of aldehyde is a
topic of concern for many decades.[8] The activation of sp2 C-CHO band of this type
still remains a challenge, there is no coupling reaction using aldehydes as
decarbonylative substrates. In this study, we describe a rhodium-catalyzed
decarbonylative coupling reaction of benzoquinoline-10-carbaldehydes with
arylboronic acids through chelation-assisted sp2 C−CHO bond activation.
2. Results and discussion
To optimize this reaction, benzoquinoline-10-formaldehyde (1aa) and phenyl
boronic acid (2aa) were initially applied in the decarbonylative cross-coupling reaction.
Based on previous research work, [7] we further investigated the effects of additives and
bases on the reaction. The results are summarized in Table 1.
Table 1 Optimization of the reaction conditions for the decarbonylative coupling reaction[a]
catalyst, additive
+
PhB(OH)2
2aa
solvent, air, 130 oC
N
Ph
3aa
N
O
H
1aa
yield (%)c
entrya,b
catalyst
additive
base
40
62
49
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
(PPh3)3RhCl
1
2
CuCl2
Cu(OAc)2
3
4
CuCl
CuI
80
75
5
Ag2O
AgBF4
52
43
89
6
7
K2CO3
Cs2CO3
K3PO4
Et3N
CuCl
CuCl
CuCl
CuCl
8
86
9
82
45
37
0
10
11
12
13
C5H5N
K2CO3
CuCl
CuCl
a
1aa
2aa
(0.15 mmol), catalyst (0.007
Reaction conditions:
(0.1 mmol),
mmol,7mol%) , additive (0.1 mmol) and base (0.1 mmol) in 1 mL of xylene in air
at 130 oC; b Reaction time:20 h; c Isolated yields.
When (PPh3)3RhCl was used as the catalyst, the desired product 3aa can be
obtained in 40% of yield at 130 °C in xylene for 20 h (entry 1). In order to further
improve the yield of product 3aa, the effect of additives on the reaction was investigated.

Several copper salts and silver salts all contributed to the reaction (entries 2-7). In
particular, CuCl provided the desired 3aa in the best yield of 80% (entry 4).
Investigations on different bases revealed that the use of a proper base can further
increase the yield of the cross-coupling reaction. K2CO3 provided the best yield of 89%
(entry 8). Cs2CO3 and K3PO3 can slightly increase the yield to 86% or 82% (entries 9,
10). However, the addition of Et3N or C5H5N inhibited the progress of this reaction
(entries 11, 12). In addition, the reaction can not occur without catalyst (PPh3)3RhCl
(entry 13).
Based on these results, the optimized catalytic system for this transformation is
(PPh3)3RhCl (7 mol%) with CuCl (1.0 eq.) and K2CO3 (1.0 eq.) in xylene at 130 °C for
20 h.
Under optimized reaction conditions, the suitable range of rhodium-catalyzed
decarbonylative activation reaction was studied. The results are shown in Table 2.
When 1aa was reacted with phenylboronic acid, the desired product 3aa was obtained
in 89% yield. The phenylboronic acids with an electron-donating group at para-position,
including a methyl, methoxy, t-butyl group, were well-tolerated and afforded the
corresponding products 3ab-3ad in good yields (83-87%).
When benzoquinoline-10-carbaldehyde (1aa) was reacted with phenylboronic
acids bearing a -F, -Cl, or -Br group at the para-position under the standard reaction
conditions, the corresponding products 3ae-3ag were obtained in moderate yields (62-
66%). In this type of rhodium-catalyzed coupling reaction, when the halide substituted
phenylboronic acids are used, the reaction product may be partially debrominated or
dechlorinated.[9] At the same time, there is an advantage that the product 3af or 3ag can
be further modified by functional groups. The phenylboronic acid substituted with a -
CF3 also can afford the product 3ah in 71% yield. However, phenylboronic acid with a
-COOEt group gave the coupling product 3ai in 61% yield. The reaction results indicate
that the phenylboronic acids with electron-donating groups are advantageous for this
reaction. [1,1'-Biphenyl]-4-ylboronic acid and naphthalen-2-ylboronic acid also reacted
with 1aa to give the corresponding coupling products 3aj and 3ak in 75% and 72%
yields, respectively.
In addition, meta-substituted phenylboronic acids were also used in this reaction.
A methyl and methoxy-substituted phenylboronic acids produced 3a1 and 3am in 83%
and 85% yield in this reaction, respectively. Phenylboronic acid with an -OCF3 or -NO2
group can also smoothly react to give the corresponding products 3an or 3ao with 74%
or 73% of yields. A methyl group ortho-substituted phenylboronic acid was also applied
in the reaction, as a result, the product 3ap was only obtained in 40% yield. The reaction
results indicate that steric hindrance inhibits the progress of the reaction, and the nature
of the substituent group has an influence on the reaction. Phenylboronic acid with
electron-donating substituents are facilitate to the reaction.
The effect of substituents on benzoquinoline-10-carbaldehydes was also
investigated. 6-Methyl-benzo[h]quinoline-10-carbaldehyde (1ba), a methyl group at
the 6-position of the benzo[h]quinoline ring, was well-tollerated and reacted with
phenylboronic acid to give 3ba in 77%. Moreover, substituents of benzoquinoline-10-
carbaldehyde with a −Ph group at the 7-position or at the 5-position both were suitable

for optimizing reaction conditions and afforded the corresponding products 3ca in 71%
yield and 3da in 75% yield, respectively. When benzoquinoline-10-carbaldehyde with
an −OMe group at the 7-position on the benzo[h]quinoline ring, the reaction also
proceeded smoothly to afford the product 3ea in 68% yield.
Table 2 Decarbonylative cross-coupling reactions of benzoquinoline-10-formaldehydes and
various arylboronic acids [a]
R2
R2
(PPh3)3RhCl (7 mol %)
1.0 eq CuCl
R1
R1
1.0 eq K2CO3
+
ArB(OH)2
xylene, air, 130 oC
N
N
Ar
N
O
H
3
1
2
N
N
N
N
F
t-Bu
OMe
Me
3ab:87%
3aa:89%
N
3ac:85%
3ad:83%
3ae:62%
N
N
N
N
Ph
CF3
COOEt
Cl
Br
3af:66%
3ag:63%
3ah:71%
3ai:61%
3aj:75%
N
N
N
N
N
NO2
OCF3
Me
OMe
3ak:72%
3al:83%
3am:85%
Ph
3ao:73%
3an:74%
OMe
Ph
N
N
N
N
N
3ea:68%
3da:75%
3ap:40%
3ba:77%
3ca:71%
a Reaction conditions: 1 (0.10 mmol), 2 (0.15 mmol), Rh(PPh3)3Cl (7 mol %), CuCl (0.10
mmol), K2CO3 (0.10 mmol) in 1 mL of xylene in air at 130 oC for 20 h; Isolated yields.
The mechanism of the reaction is similar to that of the previous studies, [6,7] the
reaction is subjected to a mechanism involving oxidative addition and reductive
elimination of rhodium complex to obtain the desired products.

Figure 1. Proposed mechanism for rhodium-catalyzed the reaction of benzoquinoline-10-
carbaldehydes with arylboronic acids.
3. Conclusion
In summary, rhodium-catalyzed C-C activation of aromatic aldehydes was
investigated. 10-Phenylbenzo[h]quinoline derivatives were synthesized by the
decarbonylative cross-coupling reaction of benzoquinoline-10-carbaldehydes with
arylboronic acids. (PPh3)3RhCl was confirmed to be a useful catalyst with CuCl and
K2CO3 as additives. Under optimized reaction conditions, a variety of functional group
substituted arylboronic acids or benzoquinoline-10-carbaldehydes are suitable for this
reaction and the desired products were obtained in moderate to good yields. Further
efforts to discover other directing groups in this catalytic reaction methodology are
currently underway in our laboratory.
4. Experimental section
General information: H NMR, C NMR and F NMR spectra were obtained on
Bruker AV 400 spectrometers with CDCl3 as solvent. For 1H NMR, the chemical shift
1
13
19
13
is reported in ppm relative to CDCl3 (δ = 7.26), for C NMR, the central CDCl3
resonance is (δ = 77.0). NMR data of known compounds are in agreement with
literature values. Elemental analyses were performed by the Elemental Analysis
Section of Tianjin University.
The starting materials 10-phenylbenzo[h]quinolines were synthesized and purified
according to the literature procedures. [7] Other chemicals or reagents were obtained
from commercial sources. Unless otherwise noted, all reactions were performed in
oven-dried glassware under an atmosphere of air. Reactions were monitored by
analytical thin layer chromatography (TLC), which was performed on 0.20 mm silica
gel plates, spots were detected by flash chromatography through UV-absorption.

Column chromatography was performed on silica gel (100-200 mesh).
General Experimental Procedure for the Preparation
Phenylbenzo[h]quinolines.
of
10-
To an oven-dried screwed vial were added substituted benzoquinoline-10-
carbaldehyde (0.1 mmol), substituted arylboronic acid (0.15 mmol), (PPh3)3RhCl
(0.007 mmol, 6.48 mg), CuCl (0. 1 mmol, 9.9 mg), K2CO3 (0. 1 mmol, 13.8 mg) and
xylene (1 mL). The mixture was vigorously stirred at 130 oC under air to the end of the
reaction. Organic solvents were removed in vacuo, and then the residue was purified
by a silica gel column chromatography to give the desired product.
Notes
The authors declare no competing financial interest.
Acknowledgment
This work was supported by grant from Research Project of Education Department of Jilin Province
(No.JJKH20180554KJ).
Appendix A. Supplementary data
Supplementary data to this article can be found online at the Publications website.
Author Information
Corresponding Author
*Email: yuxiaobo1972@126.com
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Highlights




Rhodium-catalyzed sp2 C-CHO bond activation.
A broad range of arylboronic acids are suitable.
One-step to synthesize 10-phenylbenzo[h]quinoline derivatives.
A variety of 10-phenylbenzo[h]quinoline derivatives were obtained in medium to high yields.

Author Statement
Xiaobo Yu collected the experimental data, performed data ana-lysis, and wrote the
manuscript. Guanchen Liu performed apart of data analysis. Shudong Geng performed
apart of data analysis.

R2
R2
R1
R1
(PPh3)3RhCl,CuCl,K2CO3
xylene, air, 130 oC
ArB(OH)2
+
N
N
Ar
O
H
rhodium-catalyzed C-C bond activation
one step synthesis
medium to high product yields