DOI: 10.1002/chem.201406176
Communication
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Hydrosilylation
Highly Efficient and Chemoselective Zinc-Catalyzed
Hydrosilylation of Esters under Mild Conditions
Oleksandr O. Kovalenko and Hans Adolfsson*[a]
high hazard and the formation of significant amounts of
waste.[1] The use of catalytic pathways are much more attrac-
tive from a safety and environmental point of view, and cata-
lytic hydrogenation would be the ideal reduction method.
Nevertheless, this method suffers from a number of drawbacks
and it generally requires harsh reaction conditions, which
sometimes leads to low functional-group tolerance.[2]
Abstract: A mild and highly efficient catalytic hydrosilyla-
tion protocol for room-temperature ester reductions has
been developed using diethylzinc as the catalyst. The
methodology is operationally simple, displays high func-
tional group tolerance and provides for a facile access to
a broad range of different alcohols in excellent yields.
An attractive alternative method for ester reduction is metal-
catalyzed hydrosilylation. It allows for milder reaction condi-
tions, and improved chemoselectivity has been demonstrated
in some cases.[3] Catalytic ester hydrosilylation protocols were
developed based on a range of different transition metals,
such as Ti,[4] Mn,[5] Fe,[6] Mo,[7] V,[7a] Pd,[8] Ru,[9] Rh,[10] Ir,[11] In,[12]
B[13] and Zn.[14] Nevertheless, some of these reported catalytic
systems display drawbacks in terms of requiring highly toxic
and expensive silanes, or show limitations in terms of a narrow
substrate scope. The development of an efficient, inexpensive,
highly selective, and environmentally benign system is still de-
sirable.[15]
Functionalized alcohols play an important role as building
blocks in modern organic synthesis, and are therefore fre-
quently employed in academia, the pharmaceutical industry,
and in the production of fine chemicals. A significant number
of alcohol-containing compounds demonstrate high biological
activity, whereby the hydroxy group often plays a significant
role for the action of the specific compound. Hence, function-
alized alcohols occur frequently in top-selling drugs in the cur-
rent market (Figure 1).
The chemoselective reduction of esters is a straightforward
route towards the formation of functionalized alcohols. Tradi-
tional moisture-sensitive aluminum and boron hydride re-
agents are still widely applied in ester reductions, despite the
Zinc is vital for many biological functions in humans, ani-
mals, and plants, and plays a crucial role in more than 300 en-
zymes; thus zinc is classified as a biometal.[16] The high abun-
dance of zinc, its low toxicity and moderate price make it
a very attractive metal precursor for applications in catalysis.[17]
To our knowledge, there are only two reports describing Zn-
catalyzed hydrosilylation of esters.[14] These procedures re-
quired high reaction temperatures, as well as either catalyst
pretreatment or the use of an expensive silane. We have previ-
ously reported on efficient Fe-catalyzed hydrosilylations of al-
dehydes, ketones,[18] and amides.[19] More recently we also
demonstrated an organocatalytic method for the reduction of
amides to the corresponding enamines, based on tBuOK and
(MeO)3SiH.[20] In an attempt to expand these methodologies to
include hydrosilylation of esters, we screened a number of
first-row transition metal complexes for this purpose and
found that diethylzinc displayed interesting catalytic properties
for this transformation. Herein we present an efficient, mild,
and chemoselective catalytic protocol for the reduction of
esters to alcohols, using the inexpensive and shelf-stable poly-
methylhydrosiloxane (PMHS) as the hydride source.[21]
Figure 1. Top selling drugs containing hydroxyl groups.
The initial experiments revealed that a series of different
zinc organometallic derivatives displayed high catalytic activity
for the hydrosilylation of esters. Due to the commercial avail-
ability and low cost of diethylzinc (1.0m solution in hexanes), it
was selected for further screening. Isopropyl 2-phenylacetate
was chosen as a model substrate for the optimization of the
reaction, which was conducted in a 0.5m THF solution using
[a] Dr. O. O. Kovalenko, Prof. Dr. H. Adolfsson
Department of Organic Chemistry, Stockholm University
The Arrhenius Laboratory, SE-106 91 Stockholm (Sweden)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201406176.
Chem. Eur. J. 2014, 20, 1 – 5
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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