Letter
Metal-Free Direct Oxidation of Aldehydes to Esters Using TCCA
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Silvia Gaspa, Andrea Porcheddu, and Lidia De Luca*
†
Dipartimento di Chimica e Farmacia, Universita
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degli Studi di Sassari, Via Vienna 2, 07100 Sassari, Italy
Dipartimento di Scienze Chimiche e Geologiche, Universita degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy
S Supporting Information
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*
ABSTRACT: Aromatic and aliphatic aldehydes are simply converted into esters by an efficient oxidative esterification carried
out under mild conditions. The aldehydes are converted in situ into their corresponding acyl chlorides, which are then reacted
with primary and secondary aliphatic, benzylic, allylic, and propargylic alcohols and phenols. A variety of esters are obtained in
high yields.
sters are one of the most significant functional groups
encountered in organic synthesis. They are abundant in
used. In addition, catalyst cost presents an impractical aspect for
large-scale use. An interesting alternative approach to the
esterification of aldehydes, not involving the formation of
hemiacetals, is the N-heterocyclic carbene (NHC) catalyzed
oxidative esterification of aldehydes (Scheme 1, method 2).
E
various natural products, polymers, pharmaceuticals, and
1
synthetic intermediates. Classical methods for ester synthesis
are based on nucleophilic substitution of carboxylic acid
derivatives (carboxylic halides, anhydrides, and activated esters)
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Examples of both metal-free NHC-catalyzed and NHC
2
18
with alcohols. An elegant alternative approach is the oxidative
transition-metal-catalyzed esterifications were reported. How-
esterification of aldehydes with alcohols. Common methods for
oxidative esterification of the aldehydes consist of the
ever, these methods work only with either aromatic or aliphatic
aldehydes, coupled with primary alcohols when used in large
excess.
3
formation of a hemiacetal intermediate, which is subsequently
oxidized to the ester. Over the past few decades, many
transition-metal-free direct esterifications of aldehydes through
the oxidation of hemiacetals have been reported (Scheme 1,
method 1) with several organic and inorganic oxidants such as
For these reasons, we have investigated the possibility of
developing a more general method that is suitable for the
conversion of both aliphatic and aromatic aldehydes. We have
envisioned use of an alternative method bypassing the
hemiacetal formation in order to circumvent the steric
drawbacks mentioned previously. We have searched for an
alternative to organocatalyzed oxidative esterification of
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iodine, oxone, iodine and diacetoxyiodobenzene (PhI-
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(
OAc) ), N-iodosuccinimide, sodium hypochlorite, pyridi-
2
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nium hydrobromide perbromide, and hydrogen peroxide.
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aldehydes such as NHC-, cyanide-, or 3,4,5-trimethylthiazo-
However, most of the reagents outlined above suffer from
drawbacks due to steric attributes of the aldehydes and/or the
alcohols and instability of the hemiacetal intermediate. Most of
the methods provide only methyl esters or work only with
more reactive aromatic aldehydes. Oxidative esterifications of
aldehydes catalyzed by TM catalysts have also been investigated
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lium-catalyzed esterifications to avoid the use of large excess
of oxidants and alcohols. Our goal was to carry out a general
method that would be able form acyl chlorides from both
aliphatic and aromatic aldehydes, which would then react with
all classes of alcohols to subsequently provide the correspond-
ing esters (Scheme 1, method 3). Due to our interest in using
(
Scheme 1, method 1). Effective conversion of aldehydes to
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1
1
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TCCA as an oxidant and chlorinating reagent, we checked
the viability of this reagent in the conversion of aldehydes to
esters was achieved by using rhodium-, vanadium-,
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3
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palladium-, gold-, iron-, and copper-based catalysts.
The main restrictions of these procedures are related to the
limited substrate scope, the unfavorable stoichiometric ratios of
the reagents, and the harsh and sensitive reaction conditions
Received: May 29, 2015
©
XXXX American Chemical Society
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Org. Lett. XXXX, XXX, XXX−XXX