Rhodium-catalyzed aerobic coupling between aldehydes and arenesulfinic acid salts: A novel synthesis of aryl ketones

Article abstract of DOI:10.1002/adsc.201100244

A novel rhodium-catalyzed desulfinative coupling between aldehydes and arenesulfinic acid sodium salts was developed, generating a new protocol for the synthesis of aryl ketones. Most importantly, the coupling reaction uses molecular oxygen (O₂) as the oxidant and finally releases sodium hydrogen sulfate (NaHSO₄) from the reaction system; furthermore, this reaction occurs without the need for any additives. Copyright

Full text of DOI:10.1002/adsc.201100244

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DOI: 10.1002/adsc.201100244
Rhodium-Catalyzed Aerobic Coupling between Aldehydes and
Arenesulfinic Acid Salts: A Novel Synthesis of Aryl Ketones
Honghua Rao,a Luo Yang,a Qi Shuai,a and Chao-Jun Lia,*
a
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, H3A 2K6, Canada
Fax : (+1)-514-398-3797; phone: (+1)-514-398-8457; e-mail: cj.li@mcgill.ca
Received: April 1, 2011; Published online: July 7, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100244.
Abstract: A novel rhodium-catalyzed desulfinative
coupling between aldehydes and arenesulfinic acid
sodium salts was developed, generating a new pro-
tocol for the synthesis of aryl ketones. Most impor-
tantly, the coupling reaction uses molecular oxygen
(O2) as the oxidant and finally releases sodium hy-
drogen sulfate (NaHSO4) from the reaction system;
furthermore, this reaction occurs without the need
for any additives.
As a replacement of the organometallic reagents, ar-
ylboronic acids were introduced as a much milder
arene source into the aryl ketone syntheses
(Scheme 1, route a). In 1999, an efficient palladium-
catalyzed cross-coupling reaction between arylboronic
acids and acid chlorides to generate aryl ketones was
reported by McCarthyꢀs group.[9] Several years later,
various catalytic systems were developed for aryl
ketone syntheses from arylboronic acids and nitriles
catalyzed by palladium,[10] rhodium[11] and nickel.[12]
The use of arylboronic acids as the arene sources
promises an applicable and efficient protocol for
ketone syntheses, however, the boronic acids are com-
parably expensive and not so widely available.[13] As
such, exploring and developing other arene sources
instead of arylboronic acid is still highly desirable. In
2005, Chang reported a bimetallic system for the
Keywords: aldehydes; aryl ketones; arenesulfinic
acid salts; coupling; desulfinative process; rhodium-
catalyzed reaction
The aryl ketone moiety is one of the most common direct coupling of chelating aldehydes with iodoar-
and fundamental building blocks occurring in many enes or organostannanes as the arene sources to gen-
natural products, synthetic biologically active mole- erate aryl ketones;[14] Xiaoꢀs group also disclosed an
cules,[1] and functional materials.[2] For organic chem- efficient cocatalysis of palladium-amine for the direct
ists, it is also an extremely useful functional group for coupling of aldehydes with aryl bromides (Scheme 1,
further manipulations.[3] Consequently, it continues to route b).[15] Very recently, carboxylic acids used as the
inspire the development of methods for the construc-
tion of this structural element. The traditional Frie-
del–Crafts acylation of aromatic compounds in the
presence of Lewis acids such as AlCl3 provides us
with an efficient protocol for the synthesis of aryl ke-
tones,[4] although the reaction sometimes fails with
electron-deficient arenes and generally yields the de-
sired products as isomeric mixtures.[5] The reactions of
stoichiometric organometallic compounds with acid
chlorides,[6] nitriles[7] or Weinreb amides[8] are also
popular and well-known for the preparation of ke-
tones. However, the poor functional group tolerance
and strict handling requirement of the organometallic
reagents limits their applications and thus there is a
need for milder, cleaner and catalytic alternatives.[7]
During the last decade, transition metal catalysts
have been utilized for the synthesis of aryl ketones. tones by using different arene sources.
Scheme 1. Transition-metal catalyzed synthesis of aryl ke-
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arene sources were illustrated by Larhedꢀs group via slightly decreased yields when carried out at 1608C
palladium-catalyzed decarboxylative addition to ni- and 1708C, respectively (entries 25 and 26). In order
triles affording the aryl ketones (Scheme 1, route to improve the solubility of benzenesulfinic acid
c).[16] The most outstanding advantage of this protocol sodium salt in the reaction system, H2O was intro-
is that carboxylic acids are relatively cheap and duced; however, almost no desired product was de-
widely commercially available, although it is mainly tected (entry 27).[21] And when the catalyst was re-
suitable for ortho-substituted electron-deficient ben- duced to 5 mol%, the reaction still yielded 75% of
zoic acids and aliphatic nitriles.
the desired product (entry 28).
Previously, it was known that arenesulfonyl chlor-
Hence, the scope of the direct desulfinative cou-
ides could act as aryl sources via desulfinative Heck- pling with aldehydes was explored by using 10 mol%
type reactions.[17] By contrast, the arenesulfinic acid [RhCl
AHCTUNGTRENNUNG
salts are much more stable, and may also serve as the 1 atm O2 as the oxidant at 1658C without any addi-
arene sources via the extrusion of SO2. However, to tive. As summarized in Table 2, the rhodium-cata-
the best of our knowledge, sulfinic acid salts are lyzed desulfinative coupling of benzenesulfinic acid
mainly used as sulfonylation reagents,[18] and seldom sodium salt was successfully extended to various alde-
worked as the arene sources via desulfinative reac- hyde substrates with different substituents on para-,
tions.[19] Herein, we wish to introduce a novel rhodi- meta- or ortho-position of the aromatic ring, and the
um-catalyzed coupling between aldehdyes and arene- desired aryl ketones were obtained in moderate to
sulfinic acid salts as the novel arene sources under good yields (entries 2–9). The reaction could tolerate
aerobic conditions, forming a novel strategy for aryl a range of functional groups on the aldehydes with
ketone synthesis (Scheme 1, route d).
coupling occurring in the presence of methoxy group
Initially, the coupling of p-anisaldehyde and benz- (entries 2 and 7), methyl group (entry 3), carbon-halo-
ACHTUNGTRENNUNG
um catalysts explored, only three, [RhCl
ACHTUNGTERN(NNUG COD)]2, ed groups on the aromatic ring gave lower yields (en-
[RhCl(C2H4)2]2, and RhCl(CO)(PPh3)2, afforded the tries 7–9) possibly due to the increased steric effect
A
ACHTUNGTRENNUNG
desired 4-methoxybenzophenone with 12%, 12% and (for examle, the aldehyde with methoxy group on the
22% yields, respectively (entries 7, 8 and 10). Al- ortho-position and para-position afforded the aryl
though [RhClACHTUNGTRENNUNG(C2H4)2]2 and RhCl(CO)ACHUTNTGRNE(NUGN PPh3)2 afford- ketone in 77% and 90% yields, respectively). To
ed the same or a higher yield of the desired product, expand the substrate scope, substituted arenesulfinic
the competing homodecarbonylation product,[20] acid sodium salts and alkyl aldehydes were also exam-
bis(4-methoxylphenyl)-methanone, was the major ined under the optimal conditions. To our delight,
product in these cases (entries 7 and 8). Thus, [RhCl- Substituted arenesulfinic acid sodium salt, such as p-
ACHTUNGTRENNUNG(COD)]2 was selected for further optimization. Intri- toluenesulfinic acid sodium salt, could undergo the
guingly, when air was used as the oxidant, it gave a desulfinative coupling efficiently (entry 10). An ali-
23% yield of 4-methoxybenzophenone (entry 13), phatic aldehyde, such as n-hexanal, could also react,
whereas the use of TBHP and T-HYDROꢂ gave less albeit giving the desired product in lower yields under
than 10% of the product (entries 11 and 12). Further- the present conditions (entry 11). However, the reac-
more, the reaction did not occur at all when carried tion did not occur when an aliphatic sulfinic sodium
out under argon without other additives (entry 14), in- salt such as n-BuSO2Na was treated with p-anisalde-
dicating that O2 may be a much better oxidant for hyde under the optimal conditions (entry 12).
this reaction. Indeed, the yield increased dramatically
To explore the reaction mechanism for the synthe-
to 90% when 1 atm O2 was employed as the oxidant sis of aryl ketones, the following control experiments
(entry 15). The effect of solvents was also investigat- were performed under the standard reaction condi-
ed. The yield decreased slightly when the reaction tions (Scheme 2). Coupling of p-anisaldehyde with
was carried out in benzene or PhCl (entries 16 and sodium benzenesulfonate gave no desired 4-methoxy-
17), while much lower yields were obtained in o- benzophenone and the result showed that the cou-
xylene, p-dioxane and mesitylene (entries 18–20). pling reaction did not involve the oxidation of arene-
However, there was no positive effect when K2CO3, sulfinic sodium salt to sodium sulfonate (Scheme 2,
Na2CO3, K3PO4 and NaHCO3 were added to the reac- reaction a). When benzenesulfinic sodium salt was
tion system (entries 21–24). The reaction afforded coupled with 4-cyanobenzaldehyde, the reaction yield
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Rhodium-Catalyzed Aerobic Coupling between Aldehydes and Arenesulfinic Acid Salts
Table 1. Optimization of the reaction conditions for the aryl ketone synthesis via the coupling of aldehyde with arenesulfinic
acid salt.[a]
Entry
Cat.
Solvent
Additive
Oxidant
Yield [%][b]
1
2
3
4
5
6
Ru3(CO)12
Rh6(CO)16
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
benzene
PhCl
o-xylene
p-dioxane
mesitylene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBP
TBHP
T-HYDROꢂ
air
–
O2
O2
O2
O2
O2
O2
O2
trace
trace
trace
trace
trace
trace
12
12
trace
22
<10
<10
23
–
90
82
80
50
trace
27
77
82
25
27
RhCl
Rh(CO)2acac
[RhCl(CO)2]2
[RhCl2Cp*]2
[RhCl(COD)]2
[RhCl(C2H4)2]2
Rh(COD)2BF4
RhCl(CO)(PPh3)2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
[RhCl(COD)]2
A
N
N
7
A
U
8[c]
9
A
U
E
10[c]
11
12
13
14[d]
15
16
17
18
19
20
21
22
23
24
25[e]
26[f]
27[g]
28[h]
G
A
U
A
U
A
U
A
U
A
U
A
U
A
U
–
–
–
–
A
U
A
U
A
U
A
U
K2CO3
Na2CO3
K3PO4
NaHCO3
–
–
H2O
–
A
U
O2
O2
O2
O2
O2
O2
O2
A
U
A
U
A
U
78
76
trace
75
A
U
A
U
A
U
[a]
Reaction conditions: anisaldehyde 1 (0.12 mmol), PhSO2Na (0.10 mmol), catalyst (10 mol%), solvent (0.50 mL), TBP
(4 equiv.) or TBHP (4 equiv.) or T-HYDROꢂ (4 equiv.) or air (1 atm) or O2 (1 atm), additive (2 equiv.), reaction tempera-
ture: 1658C, reaction time: 24 h.
[b]
[c]
[d]
[e]
[f]
1
Reported yields were based on PhSO2Na by H NMR using an internal standard.
Bis(4-methoxyphenyl)methanone was the major product.
Reaction was carried out under argon.
Reaction temperature: 1608C.
Reaction temperature: 1708C.
H2O (10 mL).
[g]
[h]
[RhClACHTUNGTRENNUNG(COD)]2 (5 mol%).
45% of the desired ketone, without any product being
According to the results above, a tentative mecha-
detected via the reaction of benzenesulfinic sodium nism for the aryl ketone formation was proposed
salt with the cyano group (Scheme 2, reactions b and (Scheme 3). Initially, the coordination of aldehyde 1
À
c). Furthermore, the reaction of acetophenone with to generated Rh(I) complex 3, followed by C H in-
benzenesulfinic sodium salt under the optimal condi- sertion of the aldehyde to get the Rh
N
tions yielded no 1,1-diphenylethanol (Scheme 2, reac- species 4,[22] and the oxidation of 4 by O2 may give
tion d). These results suggested that the reaction pro- the Rh
AHCTUNGTRENNUNG
cess most probably did not involve 1,2-addition of ar- plex 5 with arenesulfinic acid sodium salt effects the
ylrhodium species with aldehyde followed by libera- release of NaHSO4 (see Supporting Information),
tion of the product via a b-H elimination.
generating complex 6, which was followed by the re-
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Table 2. Scope of rhodium-catalyzed coupling between alde-
Table 2. (Continued)
Entry Aldehyde 1
hydes and arenesulfinic acid salts.[a]
Product 2
Yield
[%][b]
7
2g
2h
2i
77
50
43
79
23
0
Entry Aldehyde 1
Product 2
Yield
[%][b]
8
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
82
90
80
67
45
63
9
10
11
2c
2j
12
2k
[a]
Reaction conditions: aldehyde 1 (0.12 mmol), ArSO2Na
(0.10 mmol), catalyst (10 mol%), toluene (0.50 mL), O2
(1 atm), reaction time: 24 h, reaction temperature:
1658C.
[b]
Reported yields were based on ArSO2Na by 1H NMR
using an internal standard.
Scheme 2. Investigation of the reaction mechanism for the ketone synthesis.
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Rhodium-Catalyzed Aerobic Coupling between Aldehydes and Arenesulfinic Acid Salts
fied by silica gel column with n-hexane/ethyl acetate (40:1)
as the eluent to give the analytically pure 4-methoxybenzo-
phenone.
Acknowledgements
We are grateful to the Canada Research Chair Foundation
(to C.J. L.), the CFI, FQRNT (Center for Green Chemistry
and Catalysis), NSERC, and McGill University for support
of our research.
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In summary, we have developed a novel rhodium-
catalyzed coupling between aldehdyes and arenesul-
finic acid sodium salts, generating a new protocol for
aryl ketone synthesis. Most importantly, this desulfi-
native coupling reaction uses O2 as the oxidant and
releases NaHSO4 from the reaction system; further-
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An oven-dried reaction vessel was charged with
A
N
finic acid sodium salt (0.10 mmol, 17 mg), and 4-methoxy-
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filled with O2, dry toluene (0.5 mL) was added by syringe
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for 5 min. Then the vessel was sealed, placed into an oil
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