Rhodium-catalyzed carbonylative arylation of alkynes with arylboronic acids: An efficient and straightforward method in the synthesis of 5-aryl-2(5H)-furanones

Article abstract of DOI:10.1039/b604742d

5-Aryl-2(5H)-furanones can be synthesized by the Rh-catalyzed reactions of arylboronic acids with internal alkynes under a CO atmosphere. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b604742d

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Rhodium-catalyzed carbonylative arylation of alkynes with arylboronic
acids: an efficient and straightforward method in the synthesis of
5-aryl-2(5H)-furanones{
a
a
a
b
b
¨
Ozge Aks|n, Nurcan Dege, Levent Artok,* Hayati Tu¨rkmen and Bekir C¸ etinkaya
Received (in Cambridge, UK) 10th May 2006, Accepted 2nd June 2006
First published as an Advance Article on the web 19th June 2006
DOI: 10.1039/b604742d
dioxane–water (9 : 1) mixture (Table 1, entry 4). The presence of
water increased the formation of 4a, 5a and 6a products, while
formation of 3a was greatly reduced. Use of a pre-dried dioxane
solvent (dried over the molecular sieve 4A) lessened the formation
of benzaldehyde and 6a to trace amounts (Table 1, entry 5).
However, the presence of 1 g of the molecular sieve 4A in the
reaction medium appeared to be detrimental to the efficiency and
selectivity of the process (Table 1, entry 6).
5-Aryl-2(5H)-furanones can be synthesized by the Rh-catalyzed
reactions of arylboronic acids with internal alkynes under a CO
atmosphere.
Since Hayashi et al. reported the first Rh-catalyzed addition of
aryl- and alkenylboronic acids to a,b-unsaturated ketones,1 the
Rh-catalyzed addition of organoboron reagents to various
unsaturated systems has become increasingly popular as a method
of constructing C–C bonds. Organoboron reagents readily
undergo transmetallation with Rh to form arylrhodium(I) species
that are capable of inducing the nucleophilic arylation of various
electrophilic sites.1,2 It was also shown recently that the
Rh-catalyzed reaction of arylboronic acids with terminal a,b-
unsaturated ketones in a CO atmosphere yielded 1,4-diketones.3
In this paper, we present another example of the Rh-catalyzed
reaction of arylboronic acids: a reaction of arylboronic acids
with alkynes under a CO atmosphere to yield 2(5H)-furanones
(2-butenolides).
We postulate here a sequential insertion of CO–alkyne–CO
leading to the formation of 2(5H)-furanones (Scheme 2): It is
generally accepted that an arylrhodium(I) species (A) is formed by
the transmetallation of Rh(I) compounds with organoborons.2 The
arylrhodium(I) could then insert into CO to give an
aroylrhodium(I) species (B), which then undergoes a 1,2-addition
to the carbon–carbon triple bond. Insertion of the resulting b-aroyl
alkenylrhodium(I) complex (C) into CO, followed by a ring
closure, could form a s-furanoyl complex (D). Displacement of
Rh from the cyclic complex by protonation leads to a 5-aryl-
2(5H)-furanone molecule (3).4 The source of the proton should be
mainly the arylboronic acid itself and its decomposition products.
The enhanced formation of benzaldehyde and other side
products in moist dioxane could arise from a promoted hydrogen
transfer in the form of H+ or from a water-gas shift reaction.
The optimum reaction temperature was determined to be 80 uC
(Table 1, entries 7 and 8). The formation of by-products was
greatly reduced at this temperature. However, no activity was
observed at 60 uC in dioxane solvent. Decreasing the Rh
concentration to 1 mol% on the basis of alkyne reduced the
formation of 3a (Table 1, entry 9).
Carbonylation of a phenylboronic acid and diphenyl acetylene
mixture (in the ratio 3 : 1) in the presence of [RhCl(COD)]2 (3%
Rh) in dioxane solvent under 20 atm CO pressure at 120 uC for
16 h yielded 3,4,5-triphenylfuran-2(5H)-one (3a) as the major
product, in addition to small amounts of 2,3-diphenyl-1H-inden-1-
one (4a), 2,3-dihydro-2,3-diphenylinden-1-one (5a), and the Z- and
E-stereoisomers of 1,2,3-triphenylprop-2-ene-1-one (6a) carbonyla-
tion products (Scheme 1) (Table 1, entry 1).{
A direct carbonylation product of phenylboronic acid, benzal-
dehyde, was also produced by the reaction in significant amounts
(45 mol% on the basis of the initial phenylboronic acid quantity).
Addition of PPh3 ligand or NEt3 base to the reaction medium
significantly reduced the formation of 3a product (Table 1, entries
2 and 3). The reaction was observed to proceed less selectively in a
The reaction was more efficient for the formation of 3a when
performed in dry toluene and the formation of other side products
were minimized (Table 1, entry 10). Compared to dioxane, the
smaller moisture content of toluene and its water immiscible
nature is probably a significant factor in the diminution of the side
reactions. The reaction also proceeded successfully in the case of a
lower Rh concentration of 1% (Table 1, entry 11). Furthermore,
the catalyst loading could also be lowered to 0.3% Rh with only a
small sacrifice in the product formation (Table 1, entry 12). In
contrast to the reaction in dioxane, performing the reaction at
60 uC afforded a moderate 3a yield (Table 1, entry 13). The
method does not require large excesses of boronic acids, since the
reaction was also remarkably effective at a phenylboronic acid :
diphenyl acetylene ratio of 1.2 (Table 1, entry 14).
Scheme 1 Rhodium(I)-catalyzed carbonylative addition of phenylboro-
nic acid to diphenylacetylene.
aDepartment of Chemistry, Faculty of Science, Izmir Institute of
Technology, Urla 35430, Izmir, Turkey. E-mail: leventartok@iyte.edu.tr;
Fax: +90 232 7507509; Tel: +90 232 7507529
bDepartment of Chemistry, Faculty of Science, Ege University,
Bornova 35100, Izmir, Turkey
The synthesis of furan-2(5H)-ones (2-butenolides) are of great
interest since some derivatives of these compounds occur naturally
and possess significant biological activity.5 Numerous transition
{ Electronic supplementary information (ESI) available: Description and
NMR spectra of samples.
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Chem. Commun., 2006, 3187–3189 | 3187

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Table 1 Rhodium(I)-catalyzed reaction of phenylboronic acid and diphenyl acetylene under CO pressurea
Entry
Solvent
Rh (%)
2a : 1a
T/uC
Conversion (%)
3a (%)b
4a(%)b
5a(%)b
6a(%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Dioxane
Dioxanec
3
3
3
3
3
3
3
3
1
3
1
0.3
1
1
3
3
3
3
3
3
3
3
3
3
3
3
3
1.2
120
120
120
120
120
120
100
80
80
80
80
80
.99
.99
.99
.99
.99
.99
.99
.99
88
.99
.99
95
63
.99
70
44
39
39
74
43
80
86
63
90
85
81
43
89 (78)
5
15
7
11
4
9
2
2
2
,1
1
2
,1
2
15
15
7
24
9
16
5
3
11
,1
,1
20
,1
,1
,1
1
Dioxaned
Dioxane–H2O (9 : 1)
Dioxanee
Dioxanee,,f
Dioxanee
Dioxanee
Dioxanee
4
1
Toluenee
,1
,1
1
,1
1
,1
,1
,1
,1
,1
Toluenee
Toluenee
Toluenee
60
80
Toluenee
a
b
c
Reaction conditions: 1 mmol 1a, 10 mL solvent, 20 atm CO, 16 h. GC yield, isolated yield is given within parentheses. In the presence of
d
0.06 equiv. PPh3. In the presence of 2 mmol NEt3. Dried over molecular sieve 4A. In the presence of 1 g of molecular sieve 4A.
e
f
metal-catalyzed methods have been exploited for the synthesis of
multi-functional lactones. These methods usually involve carbo-
nylative or non-carbonylative cyclization of unsaturated reagents
functionalized by hydroxyl or carboxyl groups and the cyclo-
carbonylation of acetylenes.6 The former methods usually suffer
from the scarcity of the starting organic reagents, which require
complicated synthetic routes. In contrast, alkynes are more readily
available reagents.
via carbonylation of Z-b-iodoenones in the presence of
PdCl2(PPh3)2 catalyst and Et3N base at 100–140 uC, whereas a
more direct method, the Pd-catalyzed carbonylative addition of
aryl iodides to internal alkynes, proceeded less effectively, giving
fair-to-moderate yields.
Our methodology was well applicable to para-substituted
arylboronic acids (Table 2, entries 2–5) under the optimized
conditions given above. Electron rich arylboronic acids were
sufficiently reactive with diphenyl acetylene (Table 2, entries 2 and
3). Modest furanone product was recovered with an electron
deficient arylboronic acid, 4-(trifluoromethyl)phenylboronic acid,
at a Rh concentration of 1% (Table 2, entry 4), probably due to its
poor ability to insert carbon monoxide. However, a higher yield
for the corresponding furanone product succeeded at a Rh
concentration of 3% (Table 2, entry 5).
There are only a few reports on the carbonylative synthesis of
5-aryl-substituted furanones in the literature. The Pd(II)-catalyzed
cyclocarbonylation of 3-aryl-1-propynes and iodoarenes or acyl
chlorides, in the presence of Pd(OAc)2 (5 mol%), PPh3 ligand and
Et3N base under y20–80 atm CO pressure, led to fair-to-good
yields of E-3-arylbutenolides.7 The Rh-catalyzed cyclohydrocar-
bonylation of a-keto alkynes4c and Ru-catalyzed cyclocarbonyla-
tion of allenyl alcohols8 yielded related multi-functional lactones.
Negishi et al. employed two carbonylative methods in the
synthesis of 5-arylated furanones.9 Good yields were obtained
ortho-Tolylboronic acid failed in the carbonylative addition to
diphenyl acetylene, probably owing to steric reasons. The alkyne
conversion was about 50% with ortho-tolylboronic acid, and the
reaction yielded 1-methyl-2-((E)-1,2-diphenylvinyl)benzene as the
primary arylation product. It seems that although arylrhodium(I)
species are capable of insertion into alkynes, the ortho-substituted
aroylrhodium(I) intermediate was not reactive enough for the
1,2-addition to the carbon–carbon triple bond.
As an alkyl-substituted acetylene, 4-octyne also displayed high
activity, providing a high furanone yield (Table 2, entry 6).
Table 2 Rhodium(I)-catalyzed reaction of arylboronic acid and
alkynes under CO pressure
Entry
R1
R2
Isolated yield (%)
1
2
3
4
5
6
Ph
Ph
Ph
Ph
Ph
n-C3H7
H
CH3
OCH3
CF3
CF3
H
78 (3a)
77 (3b)
82 (3c)
40, 47 (3d)
93a (3d)
80 (3e)
Scheme 2 Proposed mechanism for the carbonylative addition of
a
With 3 mol% Rh, GC yield.
boronic acids to alkynes.
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In summary, the methodology established in this study proposes
a relatively mild and simple way for the synthesis of 5-aryl
substituted 2(5H)-furanones (2-butenolides). The application of
the process to a variety of alkyne and organoboron reagents for
the selective formation of other products, given in Scheme 1, and
for other unsaturated systems, is under way to expand the scope of
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Notes and references
{ Representative conditions for the synthesis of 3a (conditions of Table 1,
entry 14): A mixture of alkyne (1 mmol), arylboronic acid (1 mmol),
[RhCl(COD)]2 (0.005 mmol, 1 mol% Rh) and 10 mL toluene (pre-dried)
was added into a 50 mL stainless steel autoclave with a glass insert tube.
The sealed autoclave was then evacuated and purged twice successively
with 10 atm CO. Subsequently, the reactor was pressurized to 20 atm with
CO and the mixture stirred magnetically in a pre-heated oil bath. After
cooling, the reaction mixture was recovered with ethyl acetate and extracted
with a brine solution. The products were analyzed by GC and GC-MS and
isolated by column chromatography.
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Chem. Commun., 2006, 3187–3189 | 3189