Rhodium-catalyzed synthesis of esters from aryl iodides and alcohols: use of alcohols with/without the assistance of aldehydes as carbon monoxide and nucleophile sources

Article abstract of DOI:10.1039/c6ra25723b

A CO-gas-free rhodium-catalyzed alkoxycarbonylation of aryl iodide with alcohols has been developed. Alcohols, with/without the aid of an aldehyde, were used as a carbon monoxide and nucleophile source. The former synthesis afforded better yields of the alkoxycarbonylated products. Moreover, phenols also afforded phenoxycarbonylation products with high yields.

Full text of DOI:10.1039/c6ra25723b

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Rhodium-catalyzed synthesis of esters from aryl
iodides and alcohols: use of alcohols with/without
the assistance of aldehydes as carbon monoxide
and nucleophile sources†
Cite this: RSC Adv., 2017, 7, 190
*
Ju Hyun Kim, Hawon Park and Young Keun Chung
Received 24th October 2016
Accepted 1st November 2016
A CO-gas-free rhodium-catalyzed alkoxycarbonylation of aryl iodide with alcohols has been developed.
Alcohols, with/without the aid of an aldehyde, were used as a carbon monoxide and nucleophile source.
The former synthesis afforded better yields of the alkoxycarbonylated products. Moreover, phenols also
afforded phenoxycarbonylation products with high yields.
DOI: 10.1039/c6ra25723b
www.rsc.org/advances
Since the rst report by Heck et al. on the palladium-catalyzed
We studied the alkoxycarbonylation of an aryl iodide with an
reaction of carbon monoxide with aryl halides and alcohols or alcohol in the presence of a base and a rhodium catalyst. This
amines,1 transition metal catalyzed cross-coupling reactions led to the discovery of a rhodium-catalyzed, CO-gas-free alkox-
have been developed as a valuable method for creating carbon– ycarbonylation reaction of aryl iodide. The reaction occurred in
carbon bonds.2 In particular, rhodium-catalyzed carbonylation the presence of an alcohol with/without an aldehyde. The
with a variety of substrates has been studied.3 These reactions alcohol acted as both a CO and nucleophile source to afford an
require the addition of CO to the substrate, and are typically alkoxycarbonylated product. We herein report our preliminary
carried out with carbon monoxide gas. However, the use of results.
carbon monoxide is not recommended due to its toxicity and
The reaction of 4-iodoansiole (1a) with 1-octanol (2a) in the
difficulty in handling. Thus, the use of CO-releasing reagents, presence of [Rh(COD)Cl]2 (2 mol%) and DPEPhos [DPEPhos ¼
such as formic acid derivatives,4 oxiranes,5 and aldehydes6 has (oxydi-2,1-phenylene)bis(diphenylphosphine)] (4 mol%) at
been studied. Recently, Jun et al. reported7 the Pd/C-catalyzed 70 ꢀC was chosen as the synthetic model. This afforded the
carbonylative esterication of a primary alcohol with aryl alkoxycarbonylation product, octyl 4-methoxybenzoate (3aa).
chlorides in the presence of NaF. Previously, we reported the use
A yield of 50% was achieved with TMP (2,2,6,6-tetrame-
of an alcohol as a CO source in the rhodium-catalyzed Pauson– thylpiperidine) and DPEPhos as the base and ligand, respectively
Khand reaction of enynes8 and as a source of hydrogen in the (reaction conditions: [Rh(COD)Cl]2 catalyst in toluene at 120 C
ꢀ
Rh-catalyzed reductive cyclization of enynes.9 Thus, in the for 6 h). We next screened different bases and ligands (Table 1
presence of a rhodium catalyst, an alcohol can be used as a CO and ESI†). The use of DIPEA (N,N-diisopropylethylamine) or
or hydrogen source as well as a reaction medium. We therefore xantphos
(4,5-bis(diphenylphosphino)-9,9-dimethylxanthene)
decided to explore the use of an alcohol as a CO and nucleophile did not aid the yield of the reaction (entries 2 and 3). In addi-
source, in a reaction with aryl iodides, during the synthesis of tion, dehalogenated anisole was observed as a by-product in
esters (Scheme 1).
various yields depending on the reaction conditions. We attrib-
uted the formation of anisole to the presence of an Rh-hydride
intermediate (ESI or Fig. 1†). Thus, a variety of hydrogen
acceptor and oxidant were screened (entry 4 and see ESI†).
However, no noticeable enhancement in yield was observed.
Other rhodium precatalysts, such as RhCl3 and Rh(OAc)2, had no
effect on the product yield (entry 5 and ESI†). The addition of an
aldehyde enhanced the reaction, resulting in a large increase in
yield (entry 6). This was highly dependent upon the aldehyde
used (ESI†). The compound 4-chlorobenzaldehyde afforded the
Scheme 1 Proposed catalytic process in esterification.
Department of Chemistry, College of Natural Sciences, Seoul National University, best results. For example, 1 equiv. 4-chlorobenzaldehyde and 1
Seoul 08826, Korea. E-mail: ykchung@snu.ac.kr; Fax: +82-2-889-0310; Tel: +82-2-
equiv. 1-octanol afforded the ester and the anisole products in
90% and 6% yields, respectively (Table 1, entry 6). In the case of
880-6662
† Electronic supplementary information (ESI) available. See DOI:
the dodecyl aldehyde, the ester and anisole were isolated in 73%
10.1039/c6ra25723b
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Table 1 Screening the reaction conditionsa
Table
2
Yield dependence upon the ratio of 1-octanol to 4-
chlorobenzaldehydea
Entry
Variation from initial conditions
Yieldb
Entry
Alcohol (x eq.)
Aldehyde (y eq.)
Yieldb
1
2
3
4
5
6
7
8
None
50
3
13
Trace
40
90
Trace
N.R.
1
2
3
4
5
6
7
8
9
1
2
3
0
1
1
1
1.3
2
0
0
0
1
0.7
1
1.3
1.3
2
28
44
44
N.R.
56
76
72
82
80
DIPEA instead of TMP
Xantphos instead of DPEPhos
With benzoquinone
RhCl3 instead of [Rh(COD)Cl]2
With p-chlorobenzaldehyde
Without [Rh(COD)Cl]2
Without alcohol
a
Reaction conditions: 0.5 mmol of 1a, 2 mol% of [Rh(COD)Cl]2, 4 mol%
of DPEPhos, 1 equiv. of TMP (tetramethylpiperidine), 3 equiv. of 2a and
b
a
1.5 mL of toluene. GC yield using 1,3,5-trimethylbenzene as an
internal standard.
Reaction conditions: 0.5 mmol of 1a, 2 mol% of [Rh(COD)Cl]2, 4 mol%
of DPEPhos, 1 equiv. of TMP, x equiv. of 2a, y equiv. of 3a and 1.5 mL of
toluene. b Isolated yield.
and 19% yields, respectively (eqn (1)). We therefore concluded
that the addition of an aldehyde aided the formation of rhodium-
carbonyl intermediate, and increased the rate of the reaction
between the intermediate and the alkoxide to afford the ester. No
product was formed in the absence of the alcohol or the rhodium
catalyst (entries 7 and 8).
Table 3 Esters from aryl iodides and 1-octanola,b
(1)
Initially, we expected the aldehyde to act as a carbon
monoxide surrogate. To examine the role of the aldehyde in the
alkoxycarbonylation of the aryl iodide more closely, we studied
the relation between the yield of the reaction and the ratio of
octanol to 4-chlorobenzaldehyde (Table 2).
In the presence of 1 equiv. octanol, the expected ester was
isolated in 28% yield (entry 1). As the amount of octanol was
increased to 2 equiv., the yield also increased to 44% (entry 2).
Following this, an additional increase in octanol did not lead
to a further increase in yield (entry 3). As expected, no reaction
was observed in the absence of octanol (entry 4). When 1.0
equiv. octanol and 0.7 equiv. 4-chlorobenzaldehyde were used,
the yield increased to 56% (entry 5). When equal amounts (1.0
equiv.) of octanol and 4-chlorobenzaldehyde were employed,
the yield increased to 76% (entry 6). A further increase in
aldehyde to 1.2 equiv., with 1.0 equiv. octanol, led to a slight
decrease in yield (entry 7, 72%). The highest yield (82%) was
observed when 1.3 equiv. of both octanol and 4-chlor-
obenzaldehyde were used (entry 8). When 2.0 equiv. of both
octanol and 4-chlorobenzaldehyde were employed, the yield
decreased slightly to 80% (entry 9). This observation suggests
that the presence of an aldehyde aids the alkoxycarbonation
reaction of the aryl iodide in the presence of an alcohol. From
a
Reaction conditions: 0.5 mmol of 1, 2 mol% of [Rh(COD)Cl]2, 4 mol%
of DPEPhos, 1 equiv. of TMP, 1.3 equiv. of 2a, 1.3 equiv. of 3a and 1.5 mL
of toluene. Isolated yield. p-Tolualdehyde used instead of p-
chlorobenzaldehyde.
bis(diphenylphosphino)propane) as a ligand.
b
c
d
e
Some octyl ester impurities.
dppp (1,3-
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these results, the optimum conditions were established as
Aryl halides with an electron-donating group were found to
follows: 0.5 mmol of aryl iodide, 2 mol% of [Rh(cod)Cl]2, 4 be good substrates (4ba–4ha). The highest yield (94%) was
mol% of DPEPhos, 1.3 equiv. 4-chlorobenzaldehyde, 1.3 equiv. observed for the substrate with an ether group. In the cases of
ꢀ
octanol, 1 equiv. TMP, and 1.5 mL of toluene, at 130 C, for substrates having an electron-accepting group (4ka and 4la), the
18 h.
yields were rather low, and in some cases no reaction was
With the optimum reaction conditions in hands, the observed. An aryl halide bearing a chloro group afforded the
substrate scope was studied next (Table 3).
corresponding product in <50% (4ka). Moreover, <60% of the
Table 4 Esters from aryl iodides and various alcoholsa,b
a
Reaction conditions: 0.5 mmol of 1a, 2 mol% of [Rh(COD)Cl]2, 4 mol% of DPEPhos, 1 equiv. of TMP, 1.3 equiv. of 2, 1.3 eq. of 3a and 1.5 mL of
toluene. b Isolated yield.
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expected product was isolated when 4-iodo-1,10-biphenyl was
used (4la). No reaction was observed for aryl iodides having an
ester or formyl group. Aryl iodides bearing a hydroxy or amine
group did not afford expected product, presumably due to
a reaction the rhodium catalyst. However, when the functional
groups were blocked, the expected products were isolated in
reasonable yields (4ia and 4ja). Steric effects were observed in
some cases; when a methyl group was located at the meta- or
para-position, the corresponding ester was isolated in high
yields (4ca and 4da). However, in the case of 1-iodo-2-
methylbenzene, no reaction was observed. Similarly, 1-iodo-
naphthalene did not afford any products in the presence of the
ligand DPEPhos. However, when this ligand was substituted
with dppp, 67% of the expected product was isolated (4ma).
Next, we examined the reaction of the aryl iodide with other
alcohols (Table 4). Primary alcohols were studied rst. Benzyl
alcohols bearing electron-donating (Me, OMe, NMe2) or
electron-withdrawing (F, Cl, Br, NO2) functional groups were
found to be good substrates (4ab–4ai), and high yields (60–82%)
were observed. Lengthening the chain between the phenyl and
hydroxyl groups to three carbons did not have any inuence on
the yield (4aj). An internal double bond survived during the
reaction (4ak and 4al). When (E)-3-phenylpropanol or (E)-oct-5-
en-1-ol were used as an alcohol, the expected product was iso-
lated in 68% and 74% yields, respectively. In the case of (E)-oct-
5-en-1-ol, the product was a mixture of regioisomers. Unfortu-
nately, these could not be separated by conventional separation
methods. The ether group retained its position during the
reaction (4am). For secondary alcohols, including 4-phenyl-
butanol and cyclohexanol, high yields (76% and 80%, respec-
tively) were observed (4an and 4ao, respectively). However, the
tertiary alcohol 4-hydroxy-4-methylpentan-2-one afforded a poor
yield (24%) (4ap).
When the alcohol used was 4-(hydroxymethyl)phenol,
a phenol that bears two kinds of hydroxyl groups, the product (4-
formylphenyl 4-methoxybenzoate)10 was isolated in 18% yield
(4aq). The phenyl hydroxyl group was more reactive than the
benzyl hydroxyl group. In the phenoxycarbonylation reaction, the
aldehyde acted as the sole source of carbon monoxide. This
observation prompted us to study the phenoxycarbonylation of
other phenols under the same reaction conditions. Seven more
phenols were tested as substrates (4ar–4ax). The corresponding
products were isolated in the reasonable to high yields (42–88%).
Electron-decient phenols are more reactive than electron-rich
phenols. Thus, phenols, that are less reactive in the carbonyla-
tion reaction,11 are suitable reaction partners in the catalytic
reaction. Phenyl esters could therefore serve as useful acylating
reagents for the production of other carboxylate derivatives.12
On the basis of the experimental results, together with
previously studies,8,9,13 a plausible reaction mechanism can be
drawn for the alkoxycarbonylation of an aryl halide, in the
presence of a rhodium compound, with an alcohol and alde-
hyde (Scheme 2 and see ESI†). Two catalytic cycles may be
operated under our reaction conditions, namely, a reduction
path via a rhodium-hydride intermediate, and an alkox-
ycarbonylation through a rhodium-carbonyl intermediate. The
rhodium-carbonyl intermediate reacts with the aryl iodide in
Scheme 2 Proposed reaction mechanism.
the presence of an alkoxide, leading to the formation of an ester.
The rhodium-hydride intermediate reacts with the aryl halide to
afford the reduced product as a minor pathway. We predict that
the addition of an aldehyde would aid the formation of the
rhodium-carbonyl intermediate, and increase the rate of the
reaction.
Conclusions
In conclusion, we have developed
a CO-gas-free alkox-
ycarbonylation of aryl iodide in the presence of an [Rh(COD)
Cl]2/DPEPhos catalytic system and an alcohol with/without an
aldehyde. Without the aldehyde, the alcohol acted as both a CO
and a nucleophile source to afford the alkoxycarbonylated
product in moderate yield. In the presence of both the alcohol
and aldehyde, high yields of the alkoxycarbonylated product
were isolated. This occurred because the aldehyde assisted the
carbonylation reaction. When phenols were used instead of
alcohols, phenoxycarbonylation products were also isolated in
high yields. Thus, simple aldehydes and primary alcohols could
be converted to a useful CO source without any additives.
Further mechanistic studies and optimization of the reaction
conditions are in progress.
Acknowledgements
This work was supported by a National Research Foundation of
Korea (NRF) grant funded by the Korean government
(2014R1A5A1011165 and 2007-0093864). JHK and HP are
recipients of BK21 plus Fellowship.
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