Palladium-catalysed oxidative cross-esterification between two alcohols

Article abstract of DOI:10.1039/c5ob00677e

A simple palladium-catalysed oxidative cross-coupling between two different alcohols was developed. Various benzylic alcohols could couple with aliphatic alcohols in excellent yields. The use of benzyl chloride as the oxidant and the amount of aliphatic alcohol were both important for achieving the reaction selectivity.

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Palladium-catalysed oxidative cross-esterification
between two alcohols†
Cite this: DOI: 10.1039/x0xx00000x
Jianhui Xia,a Ailong Shaoa, Shan Tang,b Xinlong Gao,b Meng Gaoa,* and Aiwen Leia,b*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
the Palladium-catalysed aerobic oxidative esterification of benzylic
alcohols with aliphatic alcohols.6c, 6d It is the first time that various
aliphatic alcohols were able to be applied in oxidative cross-
esterification reactions. While in the work of Beller, a bulky mono-
phosphine ligand was used for achieving this goal.6c In our previous
work, the challenging oxidative esterification of benzylic alcohols
with long-chain aliphatic alcohols were achieved by using a special P-
olefin ligand.6c All these reactions required the use of special ligands,
which is of disadvantage for its practical application. Thus, oxidation
systems without the use of special ligands need to be developed.
Furthermore, understanding the factors that controlling the
esterification selectivity is important for future improvement of the
alcohol/alcohol oxidative cross-esterification protocol. Herein, we
would like to communicate our progress on using simple PdCl2(PPh3)2
as the catalyst for the oxidative cross-esterification between benzylic
alcohols and aliphatic alcohols (Scheme 1).
A
simple palladium-catalysed oxidative cross-coupling
between two different alcohols was developed. Various
benzylic alcohols could couple with aliphatic alcohols in
excellent yields. The use of benzyl chloride as the oxidant and
the amount of aliphatic alcohol were both important for
achieving the reaction selectivity.
Oxidative cross-coupling between two nucleophiles has now become
an important strategy for the construction of organic molecular.1 Over
the past few years, direct utilization of readily available materials such
as hydrocarbons, alcohols and amines in constructing complex
moleculars through oxidative cross-coupling has become a hot topic.2
Esters are among the most important compounds in organic chemistry.
Traditional esterification methods are based on the nucleophilic
substitution of carboxylic acid derivatives with alcohols.3 As a result,
multiple steps will be involved with production of toxic irremovable
byproduct, which is incongruent with the current demand of
environmentally-benign processes. Thus, direct oxidative
esterification between readily available aldehydes and alcohols has
been increasingly explored over the past decades.4 As aldehydes were
generally synthesized from the oxidation of corresponding alcohols,
oxidative cross-coupling between two alcohols represent the ideal
way for the synthesis of esters.5 However, this oxidative cross-
esterification approach was challenging since both of the alcohols can
be oxidized under oxidative conditions. In most cases, a poor
selectivity was observed for the oxidative coupling between two
different alcohols. Finding suitable catalytic systems for controlling
the reaction selectivity is important for the oxidative cross-
esterification reactions. Over the past decade, increasing attention has
been paid to this transformation and a few reaction systems has been
developed.6 Until now, the reaction systems for oxidative cross-
esterification between two alcohols is still limited. Developing more
reaction systems is still required for leading the esterification process
becoming much more abundant.7
Scheme 1 PdCl2(PPh3)2-catalysed oxidative cross-esterification between
benzylic alcohols and aliphatic alcohols.
It has been shown that electron-rich carbon ligands were quite
efficient for promoting transition metal catalysed selective oxidative
esterification reactions.9 Recently, our group have demonstrated that
benzyl chloride could act both as a carbon ligand and an oxidant in
the palladium catalysed selective oxidation of primary alcohols.10
With an interest in the special reactivity of benzyl chloride, we tried
to apply it in the oxidative cross-esterification reactions. When equal
amount of 4-methylbenzyl alcohol (1a) and methanol (2a) was used
by using PdCl2(PPh3)2 as the catalyst and benzyl chloride as the
oxidant, the cross-esterification product 3a and self-esterification
product 5a were both observed and obtained in similar amount. Small
amount of p-tolualdehyde (4a) could also be observed (eqn. (1)).
When we raise the amount of methanol, the yield of methyl ester
increased (Table 1, entries 1-4). An excellent selectivity was obtained
when 10 equiv of methanol was used. After obtaining good results,
Palladium catalysis has been widely used in the oxidative
transformation of alcohols.8 In 2011, Beller and our group reported
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we tried to decrease the amount of palladium catalyst. A similar yield be an effective alternative choice for the aerobic oxidative cross-
was still obtained with 5.0 mol% catalyst (Table 1, entry 5). However, esterification systems.
a decrease of yield was observed with 2.0 mol% catalyst (Table 1,
Table 2 Palladium-catalysed oxidative cross esterification between
entry 6). Thus, 5 mol% PdCl2(PPh3)2, 10 equivalent methanol were
the optimized combination for achieving this selective oxidative cross
esterification reaction.
benzylic alcohols with methanol.a
Table 1 Effect of reaction parameters for the oxidative esterification between
benzylic alcohol and methanol
aReaction conditions: 1a (0.5 mmol), 2, PdCl2(PPh3)2 (5 mol%), K2CO3 (0.5
mmol), BnCl (0.5 mmol) in THF (2 mL) at 60 oC for 20 h. bIsolated yield.
The optimized conditions were then used for the synthesis of
methyl esters from different substituted benzylic alcohols. Good
to excellent results were obtained in most cases (Table 2). Simple
benzyl alcohol showed a similar reactivity with the p-Methyl
benzyl alcohol (Table 2, entries 1-2). It is worthy of noting that
C-Cl bond was tolerated under the standard condition. The
reaction chemoselectively afforded the desired methyl ester in
excellent yield (Table 2, entry 3). In the cases of electron
deficient benzyl alcohols, decreased yield was obtained but still
with a good reaction selectivity (Table 2, entries 4-5). Some of
the benzylic alcohol substrates were left unreacted. This might
be due to the reason that electron-deficient benzylic alcohol were
harder to accomplish β-hydride elimination in the oxidation
step.6d As was expected, benzylic alcohol substituted with the
strongly
electron-donating
group
p-OMe
furnished
corresponding methyl ester in excellent yields (Table 2, entry 6).
Benzylic alcohols with methyl and methoxy groups at the metal
position all demonstrated good reactivity in this oxidative
esterification reaction. More importantly, steric hindered
benzylic alcohols such as o-tolylmethanol and 1-
naphthalenemethanol were still suitable in this transformation
with a good efficiency. Despite benzylic alcohols, cinnamyl
alcohol was also applied as the substrate in this transformation.
The desired ester could be isolated in 78% yield (Table 2, entry
12). For all reactions in Table 2, no benzaldehydes were
observed.
Since good results were obtained in the synthesis of methyl
esters, we decided to explore the oxidative esterification between
benzylic alcohols with other aliphatic alcohols (Table 3).
Preliminary results showed that this Pd-catalysed oxidation
strategy could also applied to aliphatic alcohols such as n-
propanol and isobutanol (Table 3, entries 1-2). Good yields were
obtained with both electron-deficient and electron-rich benzylic
alcohols (Table 3, entries 3-4). Thus, this reaction strategy can
a Reaction conditions: 1 (0.50 mmol), 2a (5.0 mmol), PdCl2(PPh3)2 (5.0 mol%),
K2CO3 (1.0 mmol), BnCl (1.0 mmol) in THF (2 mL) at 65 OC for 20 h. b Isolated
yield.
Based on the previous reports,4d, 10 a tentative mechanism was
brought out to understand this oxidative esterification reaction.
First, the oxidative addition of BnCl to Pd(0) generates
intermediate I-1 (BnPdCl(PPh3)2). In the next step, both benzylic
and aliphatic alcohol could undergo alcoholysis of I-1 leads to
the formation of corresponding alkoxy palladium intermediate
s
(
I-2 and I-2ʹ). Since benzylic alcohol is easier to be oxidized, a
β-hydride elimination step might take place to generate an aryl
aldehyde for I-2. Then, in situ generated aldehyde can undergo
insertion to Pd-O bond of both I-2 and I-2ʹ. In our reaction, the
2 | J. Name., 2012, 00, 1-3
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a
National Research Center for Carbohydrate Synthesis, Jiangxi Normal
University, Nanchang 330022, Jiangxi P. R. China. E-mail:
drmenggao@163.com; aiwenlei@whu.edu.cn.
substrate ratio between benzylic alcohol and aliphatic alcohol is
10 to 1. Thus, the concentration of I-2ʹ should be higher than that
of I-2. The aryl aldehyde would selectively inserts to I-2ʹ to
generate intermediate I-3, which is a hemiacetal palladium
complex. Intermediate I-3 occurs β-hydride elimination to
furnish the final ester and a palladium hydride species I-4. The
reductive elimination of I-4 releases simple toluene and
regenerates Pd(0) species.
b College of Chemistry and Molecular Sciences, the Institute for Advanced
Studies (IAS), Wuhan University, Wuhan, Hubei 430072, P. R. China.
† Electronic Supplementary Information (ESI) available: See DOI:
10.1039/c000000x/
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a Reaction conditions: 1 (0.50 mmol), 2a (5.0 mmol), PdCl2(PPh3)2 (5.0 mol%),
K2CO3 (1.0 mmol), BnCl (1.0 mmol) in THF (2 mL) at 65 oC for 20 h. b Isolated
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In conclusion, we have achieved the oxidative cross-
esterification between benzylic alcohol and aliphatic alcohols by
using PdCl2(PPh3)2 as the sole catalyst and benzyl chloride as the
oxidant. Various benzylic alcohols can selectively couple with
methanol in excellent yields. This reaction system is also suitable
for the oxidative cross-esterification with other aliphatic alcohols.
According to the proposed mechanism, the oxidant benzyl
chloride and the use of excess amount of aliphatic alcohol is
important for the selectivity of this reaction.
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This work was financially supported by the National Natural
Science Foundation of China (Nos. 21262018 and 20862007)
and the Natural Science Foundation of Jiangxi Province
(2010GZH0070).
Notes and references
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