Rhodium-catalyzed oxidative C-H arylation of 2-arylpyridine derivatives via decarbonylation of aromatic aldehydes

Article abstract of DOI:10.1021/ja105396b

A new concept for aryl-aryl coupling that involves oxidative decarbonylative coupling of aryl C-H bonds and readily available aldehydes has been developed, achieving the aryl-aryl union with complete control of reaction sites.

Full text of DOI:10.1021/ja105396b

Published on Web 08/16/2010
Rhodium-Catalyzed Oxidative C-H Arylation of 2-Arylpyridine Derivatives via
Decarbonylation of Aromatic Aldehydes
Qi Shuai, Luo Yang, Xiangyu Guo, Olivier Basle´, and Chao-Jun Li*
Department of Chemistry, McGill UniVersity, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6
Received June 24, 2010; E-mail: cj.li@mcgill.ca
as oxidant under neat conditions. To our delight, a trace amount of
the desired arylation product was detected by GC-MS (Table 1, entry
1). After the catalyst was switched to (CO)2Rh(acac), the desired
product 3aa was isolated together with biarylated product 3ba in 28%
Abstract: A new concept for aryl-aryl coupling that involves
oxidative decarbonylative coupling of aryl C-H bonds and readily
available aldehydes has been developed, achieving the aryl-aryl
union with complete control of reaction sites.
overall yield (entry 2). Other rhodium catalysts were also tested, and
none showed better activities than (CO)2Rh(acac) (entries 3-6).
Among the oxidants examined, only dicumyl peroxide was found to
The prevalence and importance of biaryl motifs in natural products,
advanced materials, and pharmaceuticals have made the preparation
of aryl-aryl bonds among the core interests of organic synthesis for
over a century.1 By far, transition-metal-catalyzed biaryl cross-coupling
reactions, which generally employ aryl halides and organometallics
as coupling partners, have served as the most common methods for
constructing biaryl unions.2 A variety of other arylation partners
involving C-C bond cleavage have also been successfully explored.
Among them, Goossen and co-workers3 reported the cross-coupling
reactions of arenecarboxylates with aryl halides through the extrusion
of CO2, which was considered as a major breakthrough in the
development of biaryl synthesis. In addition, benzonitrile,4 R,R-
disubstituted arylmethanols,5 and aryl acid derivatives6 have also been
successfully applied to biaryl synthesis under controlled conditions.
In recent years, direct arylations of unactivated arenes with preactivated
coupling partners (aryl halides and organometallic reagents) via C-H
activation have emerged as attractive alternatives to classical methods
(Scheme 1, route a).7 More recently, more challenging oxidative cross-
couplings of two simple arenes have been achieved and developed,
affording biaryl products with high atom economy (Scheme 1, route
b).8 While such couplings are conceptually ideal, controlling the
regioselectivity of unactivated aryl C-H bonds is still a major
challenge. Herein, we present a new concept for aryl-aryl coupling
that inVolVes oxidatiVe decarbonylatiVe coupling of aryl C-H bonds
and aldehydes, achieVing the aryl-aryl union with complete control
of reaction sites (Scheme 1, route c).
be as effective as TBP (entries 7-9). Because of the higher price of
dicumyl peroxide and the difficulty of removing 2-phenylpropan-2-ol
after the reaction, TBP was chosen as the oxidant for further
optimizations. When the reaction was performed in various solvents,
the yield improved significantly (entries 10-13), with chlorobenzene
(entry 13) being the best. Shortening the reaction time decreased the
yield (entry 14), whereas a longer reaction time did not improve the
yield (entry 15). Finally, the use of an additional 0.5 equiv of 2a
increased the yield to 81% (entry 18).
Table 1. Optimization of Reaction Conditionsa
entry
catalyst
oxidant
solvent
yield (%)b
1
2
3
4
5
6
7
8
[Ru(COD)Cl2]n
(CO)2Rh(acac)
Rh(COD)2BF4
[Rh(COD)Cl]2
[(CO)2RhCl]2
RhCl3
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
(CO)2Rh(acac)
TBP
TBP
TBP
TBP
TBP
TBP
neat
neat
neat
neat
neat
neat
neat
neat
trace
28c
0
11
19
18
27
13
18
55
45
48
61
52
58
70
77
81
72
dicumyl peroxide
tert-butyl peracetate
(PhCOO)2
TBP
TBP
TBP
TBP
TBP
TBP
TBP (1.5 equiv)
TBP (2.0 equiv)
TBP (2.5 equiv)
TBP (3.0 equiv)
9
neat
10
11
12
13
14d
15e
16f
17f
18f
19f
dioxane
anisole
toluene
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
Scheme 1. Arene-Arene Coupling via C-H Activation
a Conditions: 1a (0.1 mmol, 14.6 µL), 2a (0.25 mmol, 31.0 µL),
(CO)2Rh(acac) (0.01 mmol, 2.6 mg), TBP (0.2 mmol, 37.6 µL), solvent
(0.2 mL), argon, 150 °C, 24 h. b NMR yield (3aa + 3ba). c Isolated
yield. d For 12 h. e For 48 h. f 2a (0.3 mmol, 37.2 µL) was used.
On the basis of our previous studies of cross-dehydrogenative-
coupling (CDC) reactions9 and decarbonylative coupling of aldehydes
and terminal alkynes,10 we postulated that readily available aromatic
aldehydes could be used as potential arylation partners with arenes
via decarbonylative CDC coupling by employing an appropriate
oxidant. We began our investigation by testing the reaction of
2-phenylpyridine (1a) with anisaldehyde (2a) in the presence of
catalytic amounts of ruthenium catalyst using tert-butyl peroxide (TBP)
Under the optimized reaction conditions, the scope and generality
of this oxidative cross-coupling reaction through decarbonylation
of aromatic aldehydes was explored. Electron-rich aromatic alde-
hydes with a methoxy group at either the para or meta position
proved to be good substrates for this transformation, affording the
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12212 J. AM. CHEM. SOC. 2010, 132, 12212–12213
10.1021/ja105396b  2010 American Chemical Society

C O M M U N I C A T I O N S
corresponding arylated products in good yields (Table 2, 2a and
2b). p-Tolualdehyde (2c), albeit also effective, furnished the
products in moderate yields because of the reaction between the
methyl group and the oxidant TBP. 4-Phenylbenzaldehyde (2d) and
benzaldehyde (2e) coupled with 2-phenylpyridine (1a) efficiently.
Having an electron-withdrawing cyano substituent at the para
position, aldehyde 2f gave a slightly lower yield of decarbonylative
coupling products. However, methyl 4-formylbenzoate (2g) was
found to couple with 1a efficiently and afforded the desired product
in good yield. Notably, the fluoro, chloro, and bromo moieties
(commonly used for cross-coupling reactions) in benzaldehydes 2h,
2i, 2j, and 2k were all tolerated under this novel coupling and
afforded the targeted products in moderate to good yields, making
further elaborations of the corresponding biaryl products possible.
The substituents on the phenyl ring in the 2-arylpyridine derivatives
1b, 1c, 1d, and 1e did not affect the efficiency of the coupling
reactions, and good yields of the desired products were obtained.
A tentative mechanism for this novel coupling is proposed in
Scheme 2. Initially, oxidative addition of aldehyde 2 to the Rh(I)
center 4 generates species 5, which undergoes extrusion of CO
at elevated temperature to give 6. Next, 6 reacts with 1a through
C-H bond activation, which is followed by dehydrogenation
promoted by TBP to give 7. Finally, reductive elimination of
intermediate 7 affords the target biaryl product 3a and regener-
ates the Rh(I) catalyst 4.
Scheme 2. Tentative Mechanism for the Oxidative Arylation of
2-Phenylpyridine with Aryl Aldehydes
Table 2. Oxidative Decarbonylative Arylation of 2-Arylpyridinesa
In conclusion, we have discovered a novel method for the
synthesis of biaryls that employs aromatic aldehydes and 2-arylpy-
ridine derivatives as cross-coupling partners in the presence of an
oxidant and proceeds via the extrusion of CO. Aryl halides are
tolerated under the reaction conditions. The mechanism and
synthetic applications of this aryl-aryl coupling as well as the
extension of such a coupling to acrolein derivatives and other
substituted benzenes are under further investigation.
Acknowledgment. We are grateful to the Canada Research
Chair (Tier I) Foundation (to C.-J.L.), NSERC, CFI, and McGill
University for their support of our research.
Supporting Information Available: Representative experimental
procedures and characterization data for all compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
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determined by H NMR analysis are given in parentheses. c 1c (0.2 mmol,
1
35.8 mg), 2a (0.3 mmol, 37.2 µL), and TBP (0.25 mmol, 47.0 µL) were used.
JA105396B
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J. AM. CHEM. SOC. VOL. 132, NO. 35, 2010 12213