Angewandte
Chemie
DOI: 10.1002/anie.201205154
Homogeneous Catalysis
Efficient Reduction of Esters to Aldehydes through Iridium-Catalyzed
Hydrosilylation**
Chen Cheng and Maurice Brookhart*
Reduction of esters to aldehydes is challenging since the
aldehyde products are often more reactive toward nucleo-
philic hydride reducing agents than the starting esters.[1]
Hence, bulky reducing agents such as diisobutylaluminum
hydride (DIBALH) or lithium tri-tert-butoxyaluminum hy-
dride have been developed for this transformation.[2] How-
ever, these reagents are usually toxic, air- and moisture-
sensitive, require exigent reaction conditions, and are not
compatible with many functional groups. In addition, even
these reagents often result in over-reduction of substrates.
Alternatively, reduction of carbonyl derivatives can be
achieved through catalytic hydrosilylation followed by
hydrolysis of the silyl group.[3] For example, hydrosilylation
of ketones and aldehydes followed by acidic or basic workup
affords secondary and primary alcohols.[3e,f] This strategy has
also been widely applied to the reduction of esters to alcohols
or ethers (Scheme 1).[4] In contrast, there have been very few
with Ph3SiH, although the reactions were accompanied with
substantial over-reduction to silyl ethers and alkanes.[5c] Here
we report a simple and highly efficient method for reduction
of esters to aldehydes via silyl acetal intermediates generated
by iridium-catalyzed hydrosilylation. The catalyst, [{Ir-
(coe)2Cl}2], (coe = cyclooctene) can be easily prepared and
is commercially available, and this reduction system exhibits
high conversion at low catalyst loading (down to 0.1 mol%)
and good functional group compatibility.
Previously we showed that the binuclear iridium complex
[{Ir(coe)2Cl}2] is an efficient catalyst for reduction of secon-
dary amides to secondary amines through hydrosilylation
using diethylsilane.[6] For reduction of ethyl benzoate we
screened several silanes, including diethylsilane, in C6D6 at
room temperature (Table 1). Consistent with previous results
concerning amide reduction, diethylsilane proved most effec-
Table 1: Screening experiment for hydrosilylation of esters.[a]
Entry
Silane
t [h]
Conversion [%]
1
2
3
4
5
6
7
8
Et2SiH2
Et3SiH
2
12
12
12
12
12
24
5
>99
0
TMDS[b]
PMHS[c]
EtMe2SiH
(EtO)3SiH
Ph2SiH2
PhMeSiH2
0
0
0
0
23
96
Scheme 1. Reduction of esters through catalytic hydrosilylation.
examples of controlled reduction of esters to silyl acetals,
which upon hydrolysis give aldehydes.[5] One such example
employed a ruthenium carbonyl complex at high temperature
(1008C) and demonstrated limited substrate scope.[5a]
Another method requires using 2-pyridinyl esters as substrate
and cannot be applied to “simple” esters.[5b] Finally, B(C6F5)3
has been used to catalyze reduction of esters to silyl acetals
[a] Reaction conditions: ethyl benzoate (0.1 mmol) with [{Ir(coe)2Cl}2]
(0.15 mmol) and silane (1.5 equiv) in C6D6 (0.35 mL). Reactions were run
at room temperature. Conversions were determined by 1H NMR
spectroscopy. [b] 1,1,3,3-Tetramethyldisiloxane (1.5 equiv, 3 equiv SiH
functionality). [c] Polymethylhydrosiloxane (5 equiv), assuming MW=60
for each SiH functionality.
[*] C. Cheng, Prof. Dr. M. Brookhart
Department of Chemistry
tive, and hydrosilylation of the carbonyl double bond took
place rapidly at room temperature to afford the diethylsilyl
acetal (Table 1, entry 1). Several tertiary silanes screened
proved to be ineffective (Table 1, entries 2–6), whereas
bulkier secondary silanes react more slowly than diethylsilane
(entries 7 and 8).
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599-3290 (USA)
E-mail: mbrookhart@unc.edu
[**] We gratefully acknowledge the financial support of the NSF as part
of the Center for Enabling New Technologies through Catalysis
(CENTC, Grant No. CHE-0650456). We thank Thomas Lyons for
useful comments. A provisional patent on this work has been
submitted.
À
In ester reductions studied here, cleavage of the C O
bond of the acetal intermediates by diethylsilane to give silyl
ethers occurs much more slowly than the initial hydrosilyla-
tion and generally requires higher temperatures.[7] Hence,
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 1 – 4
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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