Phosphine ligand triggered oxidative decarbonylative homocoupling of aromatic aldehydes: Selectively generating biaryls and diarylketones

Article abstract of DOI:10.1039/c0cc04921b

A novel rhodium-catalyzed oxidative decarbonylative homocoupling of aromatic aldehydes to generate biaryls and diarylketones selectively and efficiently, triggered by the choice of different phosphine ligands.

Full text of DOI:10.1039/c0cc04921b

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COMMUNICATION
Phosphine ligand triggered oxidative decarbonylative homocoupling of
aromatic aldehydes: selectively generating biaryls and diarylketonesw
Luo Yang, Tieqiang Zeng, Qi Shuai, Xiangyu Guo and Chao-Jun Li*
Received 12th November 2010, Accepted 13th December 2010
DOI: 10.1039/c0cc04921b
A novel rhodium-catalyzed oxidative decarbonylative homo-
coupling of aromatic aldehydes to generate biaryls and diaryl-
ketones selectively and efficiently, triggered by the choice of
different phosphine ligands.
Scheme 1 Phosphine ligand triggered oxidative decarbonylative
homocoupling.
The abundance of the biaryl motif in natural products, pharma-
ceuticals and materials has positioned aryl–aryl formation high
1
on the agenda of synthetic chemists. Although there exists a
variety of routes for the construction of aryl–aryl unions,
arguably the most common method is through the homo- and
cross-coupling of (pseudo)aryl halides (Ar–X) and aryl metal-
loids (Ar–M) as exemplified by the Ullmann reaction, the
Kumada reaction, the Negishi reaction, the Suzuki reaction
Scheme 2 Aldehyde C–H bond activation and decarbonylative
homocoupling.
1,2
13 14
the arylmetal hydride 5 can react with alkene, alkyne and
and the Stille reaction. While the transition-metal-catalyzed
direct arylation of aryl halides (Ar–X) or metalloids (Ar–M) with
an unfunctionalized arene (Ar–H) represents a recent alternative
1
5
arene to give (oxidative) decarbonylative coupling products.
We postulated that the transmetalation between two arylmetal
hydride 5 or acylmetal hydride 4 and arylmetal hydride 5
would generate the diaryl–metal complex 6 and acyl–aryl–
3
strategy for biaryl synthesis, more attractive oxidative cross-
couplings of two simple electron-rich arenes (Ar–H) have been
achieved, affording biaryl products efficiently and economically
0
metal complex 6 , respectively, which will lead to the novel
4
albeit still having challenges in controlling regioselectivity.
C–C bond formation product, biaryls and diarylketones, after
reductive elimination.
On the other hand, arylketones are also important building
5
blocks in both natural products and functional materials. The
With these objectives in mind, we first tested the reaction of
p-methoxybenzaldehyde catalyzed by the Wilkinson’s catalyst
classical routes to the synthesis of arylketones rely on the
6
oxidation of the corresponding secondary alcohols, Friedel–
3 3
[(PPh ) RhCl] in the presence of tert-butyl peroxide (TBP),
7
Crafts acylation of aromatic compounds and transition-metal-
since the catalyst has been the most widely used one for the
16
decarbonylation of aldehydes. Gratifyingly, the decarbonylative
8
catalyzed arylation of acyl chlorides, nitriles or aldehydes.
9
10
More direct synthesis of diarylketones from readily available
compounds will be highly desired. Herein, we report an
unprecedented oxidative decarbonylative homocoupling of aromatic
aldehydes to produce biaryls and diarylketones selectively utilizing
cheap and abundant aldehydes as the starting materials triggered by
the choice of different phosphine ligands (Scheme 1).
homocoupling product 2a and a significant amount of the
1
diarylketone product 3a was observed by H NMR, with an
overall yield of 82% in 1 : 1 ratio (Table 1, entry 1).
In order to increase the selectivity of this reaction, a detailed
optimization was conducted. First, the catalytic activities of
different rhodium sources for the reaction were investigated by
It has been well studied that the oxidative addition of a
transition metal (M) across the aldehyde C–H bond will
using PPh as the ligand (Table 1, entries 1–10). In all these cases,
3
the decarbonylative homocoupling products 2a and 3a can be
detected with varied yields with the biaryl 2a being the main
1
generate an acylmetal hydride 4 (Scheme 2); decarbonylation
1
of which followed by reductive elimination of the resulting
2 2
product. [(CO) RhCl] gave a slightly better result than the other
1
2
arylmetal hydride 5 leads to a simple arene (Ar–H). Alter-
rhodium catalysts (Table 1, entry 2), affording a 85% NMR yield
with the ratio of 2a and 3a being 72 : 28. Then, bidentated
phosphine ligands with different bite angles were applied to
this decarbonylative homocoupling (entries 11–17). To our
delight, the selectivity reversed when binap, dppe and dppbe
natively, it has been exemplified by our previous results that
Department of Chemistry and FQRNT Center for Green Chemistry
and Catalysis, McGill University, Montreal, QC, Canada H3A 2K6.
E-mail: cj.li@mcgill.ca; Fax: +1 514-398-3797; Tel: +1 514-398-8457
w Electronic supplementary information (ESI) available: Experimental
details and spectral data. See DOI: 10.1039/c0cc04921b
[1,2-bis(diphenylphosphino)benzene] were used as the ligand,
with the diarylketone 3a being the main product (entries 11,
13, 14 and 17). When dppe was used as the ligand for
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 2161–2163 2161

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Table
coupling of aldehydes
1
Optimization of the oxidative decarbonylative homo-
Table 2 Oxidative decarbonylative homocoupling of aldehydes for
a
the preparation of biaryls
a
b
Ligand
(mol%)
Yield Ratio
2a + 3a 2a/3a
b
Entry
Ar
Product
Yield (ratio)
Entry Rh (mol%)
(PPh RhCl (2.5)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
4-CH
3-CH
4-CH
4-AcO–C H
6 4
6 5
C H
4-F–C H
6 4
4-Cl–C
3-Cl–C
3
O–C
O–C
–C H
6 4
6
H
H
4
2a + 3a
2b + 3b
2c + 3c
2d + 3d
2e + 3e
2f + 3f
2g + 3g
2h + 3h
2i + 3i
2j + 3j
2k + 3k
2l + 3l
82 (72 : 28)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
3
)
3
—
—
PPh
82
78
85
67
78
69
75
73
67
86
69
67
50 : 50
76 : 24
72 : 28
72 : 28
66 : 34
79 : 21
61 : 39
72 : 28
73 : 27
70 : 30
27 : 73
74 : 26
o2 : 98
o2 : 98
68 : 32
62 : 38
o2 : 98
81 : 19
67 : 33
89 : 11
57 : 43
3
3
6
4
81 (98 : o2)
72 (80 : 20)
65 (94 : 6)
66 (89 : 11)
87 (86 : 14)
82 (86 : 14)
71 (93 : 7)
78 (95 : 5)
72 (98 : o2)
72 (89 : 11)
59 (94 : 6)
(CO) RhCl(PPh
[(CO) RhCl] (1.25)
(CO) Rh(acac) (2.5)
[Cp*RhCl (1.25)
[(COD) RhOH] (1.25)
(COD) Rh(BF ) (2.5)
[Rh(OAc)
RhCl (2.5)
HRh(PPh
2
3
)
2
(2.5)
2
2
3
(6)
(6)
(6)
(6)
(6)
(6)
(6)
2
PPh
PPh
PPh
PPh
PPh
PPh
—
binap (3)
dppm (3)
dppe (3)
dppe (3)
dppp (3)
dppb (3)
3
3
3
3
3
3
2 2
]
2
2
6
H
H
4
2
4
2 2
]
(1.25)
6
4
3,4-Cl
4-CN–C
4-CF –C
4-MeO C–C
2
6
–C H
3
3
10
11
12
1j
1k
1l
6
H
4
0
1
2
3
4
5
6
7
8
9
0
1
3 4
)
(2.5)
3
6 4
H
[(CO)
[(CO)
[(CO)
2
2
2
RhCl]
RhCl]
RhCl]
2
(1.25)
(1.25)
(1.25)
(1.25)
(1.25)
(1.25)
(1.25)
(1.25)
(1.25)
(1.25)
2
6
H
4
2
2
72
a
Conditions: Method A, aldehyde
1 (0.2 mmol), 1.25 mol%
c
80
[(CO)
2
RhCl]
2
[(CO)
2
RhCl] , 6.0 mol% PPh , TBP (2.5 equiv., 0.5 mmol), reacted
2
3
[(CO)
[(CO)
[(CO)
[(CO)
[(CO)
[(CO)
2
2
2
2
2
2
RhCl]
RhCl]
RhCl]
RhCl]
RhCl]
RhCl]
2
2
2
2
2
2
72
68
b
for 12 h at 150 1C under argon. Isolated yield.
dppbe (3) 44
PBu
PCy
—
3
(6)
(6)
38
20
substrates, which makes this decarbonylative homocoupling
valuable for the synthesis of halogen substituted biaryls amenable
for post-functionalizations. Electron-deficient aldehydes sub-
stituted by cyano, trifluoromethyl and methylcarboxylate
3
47
c
58
[(CH
2
QCH
2
)
2
RhCl]
2
(1.25) dppb (3)
a
Conditions: 1a (0.2 mmol), [Rh], phosphine ligand, TBP (0.5 mmol) and
benzene (0.4 mL), reacted for 12 h at 150 1C under argon, unless otherwise
noted. Determined by 1H NMR analysis of the crude reaction mixture
(1f–1i) can also take part in this novel homocoupling with
b
moderate yields and good chemoselectivity. When o-tolualdehyde
c
using an internal standard. Reaction performed at 160 1C.
was used as the substrate under the standard reaction conditions
(
2 2 3
[(CO) RhCl] /PPh ), the corresponding diarylketone was
the main product instead of biaryl. This can be explained by
the increased steric effect, slowing the decarbonylation of the
ortho-substituted aldehyde than the unsubstituted one.
Similarly, under the optimized conditions for the preparation of
diarylketone compounds (Method B: 1.25 mol% [(CO) RhCl] ,
[
2 2
(CO) RhCl] , the decarbonylative homocoupling of p-methoxy-
benzaldehyde produced diarylketone 3a in 72% yield after
reacted for 12 h at 150 1C (entry 13) and no biaryl product can
be detected under these conditions. The yield of diarylketone 3a
can be further increased to 80% after the reaction temperature
was raised to 160 1C (entry 14). Monophosphine ligands such as
PBu and PCy can also be used in this reaction albeit leading
2
2
3.0 mol% dppe, 2.5 equiv. TBP, reacted for 12 h at 160 1C), the
substrate scope for the preparation of diarylketones was explored.
As shown by the results in Table 3, various electron-rich aromatic
aldehydes substituted by alkyl and alkoxy reacted smoothly to
produce the corresponding homocoupling products (Table 3,
entries 1–7). Among them, p-, m- and o-methyl benzaldehydes
3
3
to a lower yield (entries 18 and 19), possibly because these
trialkylphosphine ligands are less stable under the oxidative
conditions. In the absence of
rhodium catalyst [(CO) RhCl] itself can also promote this
decarbonylative homocoupling to give 2a and 3a in much lower
yields than in the presence of PPh (entry 20). Using
RhCl(CH QCH as a pre-catalyst resulted in both lower
a phosphine ligand, the
2
2
Table 3 Oxidative decarbonylative homocoupling of aldehydes for
the preparation of diarylketones
a
3
[
2
2 2 2
) ]
yield and selectivity (entry 21). Under the best conditions
indicated by entries 3 and 14, in the absence of TBP, anisole
was the only observed product, with most of the starting material
recovered. Other organic solvents such as chlorobenzene,
b
Entry
Ar
Product
Yield
1
,4-dioxane and 1,2-dichloroethane can also be used as the
1
2
3
4
5
6
7
8
9
1a
1b
1m
1c
1n
1o
1p
1e
1f
4-CH
3
O–C
O–C
6
H
H
4
3a
3b
3m
3c
3n
3o
3p
3e
3f
78
76
74
71
81
82
75
49
50
56
reaction media, albeit not as good as benzene (ESIw).
Under the optimized conditions for the preparation of biaryl
3-CH
3
6
4
n
4- C H O–C H
6
5
11
4
4-CH
3-CH
2-CH
3
3
3
–C
–C
–C
6
6
6
H
H
H
4
4
4
compounds (Method A: 1.25 mol% [(CO)
2 2
RhCl] , 6.0 mol%
PPh , 2.5 equiv. TBP, reacted for 12 h at 150 1C), the substrate
3
scope of this novel homocoupling was explored. As shown by the
results in Table 2, various aromatic aldehydes with electron-rich
substituents such as methyl, methoxy and acetoxy (1a–1d)
reacted smoothly to produce the corresponding homocoupling
products (Table 2, entries 1–4). Benzaldehyde (1e) also reacted
efficiently (entry 5). Aldehydes with weak electron-withdrawing
substituents such as fluoro and chloro (1f–1i) were also feasible
2,4-(CH
C H
6 5
4-F–C
3-Cl–C
3
)
2
–C
6
H
3
6
H
4
1
0
1h
6
H
4
3h
a
Conditions: Method A, aldehyde
RhCl] , 3.0 mol% dppe, TBP (2.5 equiv., 0.5 mmol), reacted
for 12 h at 160 1C under argon. Isolated yield.
1 (0.2 mmol), 1.25 mol%
[(CO)
2
2
b
2
162 Chem. Commun., 2011, 47, 2161–2163
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2
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homocoupling.
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(
1c, 1n and 1o) were examined and this homocoupling was
not sensitive to the increased steric hindrance (entries 4–6).
Benzaldehyde, 4-fluorobenzaldehye and 3-chlorobenzaldehyde
4
(1e, 1f and 1h) can also take part in this homocoupling albeit
with slightly lower yields because of oxidations to the corres-
ponding benzoic acid derivatives (entries 8–10). It is worth noting
that, in all cases, almost no biaryl products were detected by
5 For reviews, see: (a) J. Tsuji, Transition Metal Reagents and
Catalysts, Wiley, New York, 2004; (b) F. Diederich and
P. J. Stang, Metal-Catalyzed Cross-Coupling Reactions,
Wiley-VCH, Weinheim, Germany, 1998.
1
H NMR of the crude reaction mixtures, which illustrated that the
6
(a) M. Hudlicky, in Oxidations in Organic Chemistry, ACS
Monograph 186, American Chemical Society, Washington, DC,
oxidative decarbonylative homocoupling using the Method B had
an excellent chemoselectivity for the diarylketones.
1990; (b) R. C. Larock, Comprehensive Organic Transformations,
VCH, New York, 1989, p. 591.
A tentative mechanism to rationalize this novel rhodium-
catalyzed oxidative decarbonylative homocoupling is illustrated in
Scheme 3. First, the rhodium(I) catalyst undergoes oxidative
addition with the aldehyde C–H bond rapidly to produce
acylrhodium hydride 7, which is oxidized by TBP to yield
acylrhodium complex 8. Decarbonylation of acylrhodium
complex 8 gives arylrhodium complex 9. Second, when
PPh3 is used as the ligand, transmetalation between two
arylrhodium 9 complexes gives complex 10, which upon
reductive elimination releases biaryl product 2. Similarly,
when dppe is used as the ligand, transmetalation between
acylrhodium complex 8 and arylrhodium complex 9 forms
complex 11, which upon reductive elimination releases
diarylketone product 3 and regenerates the rhodium catalyst
for further reactions. The difference is that when dppe is used
as the ligand, the decarbonylation of the acylrhodium complex
7
(a) G. Olah, Friedel–Crafts and Related Reactions, Interscience
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1
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8
to generate the arylrhodium complex 9 is much more difficult
caused by the decreased dissociation ability of metallacyclic
1
1,17
Rh complex 8 (L = dppe).
Once the arylrhodium
complex 9 is formed, it will undergo transmetalation with
the acylrhodium complex 8 rapidly to generate complex 11.
In summary, we have developed a novel rhodium-catalyzed
oxidative decarbonylative homocoupling of aromatic aldehydes to
generate biaryls and diarylketones selectively and efficiently,
triggered by the choice of different phosphine ligands. Unlike
previous methods using aryl halide or acyl halide, the current
reaction utilizes cheap and abundant aldehydes as starting
material. Application of this novel method to aliphatic aldehydes
and cross decarbonylative coupling of aromatic aldehydes is under
further investigation.
1
7
2
25; (b) C.-H. Jun, E.-A. Jo and J.-W. Park, Eur. J. Org. Chem.,
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We are grateful to the Canada Research Chair (Tier I)
Foundation (to CJL), CFI, and NSERC for partial support
of our research.
2
11For a highlight of our work, see: (d) C. L. Allen and
J. M. J. Williams, Angew. Chem., Int. Ed., 2010, 49, 1724.
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1
1
Notes and references
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This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 2161–2163 2163