DOI: 10.1002/chem.201100800
Zinc-Catalyzed Chemoselective Reduction of Esters to Alcohols
[
a]
Shoubhik Das, Konstanze Mçller, Kathrin Junge, and Matthias Beller*
Functionalized alcohols are of importance for the manu-
facture of pharmaceuticals, agrochemicals, dyes, and numer-
ous bioactive compounds (see below for selected examples
of bioactive alcohols). Regarding their synthesis, the reduc-
tion of esters to the corresponding alcohols provides a
effective for this reduction. Nevertheless, the development
of a cost-effective, efficient, and highly selective catalyst for
this transformation is still desirable because most of the
known protocols either require expensive silanes or have
limited functional group tolerance.
[1]
straightforward access. Notably, for special products and
on a laboratory scale, traditional boron and aluminium hy-
The abundant availability, low toxicity and biomimetic
[17]
nature of zinc makes it a highly attractive candidate for
catalysis. Based on our recent study on the zinc-catalyzed re-
[2]
dride-mediated reductions still prevail. Compared to these
stoichiometric reactions, catalytic methods offer more versa-
[18]
duction of amides,
herein we report a general and im-
proved catalytic hydrosilylation of esters to generate alco-
hols. Notably, excellent chemoselectivity is achieved in the
presence of other reducible functional groups.
Initially, the reaction of methyl phenylacetate 1a with
(
EtO) MeSiH in THF was investigated as a model system to
2
identify and optimize the critical reaction parameters
Table 1). As expected, no reaction occurred in the absence
of any catalyst (Table 1, entry 1). In contrast, 10 mol% of in-
expensive Zn(OAc) was an excellent catalyst and gave 2-
(
AHCTUNGTRENNUNG
2
phenylethanol 1b in 90% yield, after hydrolysis with 25%
KOH in methanol (Table 1, entry 2). However, after apply-
ing lower catalyst loadings of 7.5 and 5 mol% the yield de-
creased to 70 and 45%, respectively (Table 1, entries 3 and
4
). Surprisingly, other zinc sources such as ZnF , ZnBr ,
2 2
[3]
tile strategies and might allow for improved selectivity.
ZnI , Zn
A
H
N
T
E
U
(ClO ) ·6H O, and Zn
A
H
N
T
N
U
(NO ) ·6H O were inactive
2
4
2
2
3
2
2
Evidently, catalytic hydrogenation represents an ideal
method for the reduction of esters, but sometimes low func-
tional group tolerance and the necessity to use high pressure
and only Zn(2-ethyl hexanoate) and ZnCl showed a little
2 2
activity (Table 1, entries 13–19). Other metal acetates (such
as Cu and Fe) were also inactive (Table 1, entries 11–12). To
exclude the influence of potential precious metal contami-
nants in the catalyst precursor we also used zinc acetate
from different suppliers (ABCR, Sigma Aldrich, and
Acros). In all cases similar yields of the product were ob-
tained in the model reaction.
[4]
autoclaves impair its general use. Although heterogeneous
hydrogenation of fatty esters is performed in industry on
[5]
bulk scale, it needs high temperatures (200–3008C) along
with high hydrogen pressures (200–300 atm). On the other
hand, homogeneously catalyzed hydrogenations have been
[6]
only scarcely investigated until recently.
Next, we started to investigate the influence of different
Relative to hydrogenations, catalytic hydrosilylations are
a well-accepted tool, which are operationally simple to per-
form and often allow for improved chemoselectivity and re-
silanes on the reaction. In addition to (EtO) MeSiH, several
2
silanes such as PhSiH , PhSiH , and (EtO) SiH were also
3
2
3
active (Table 1, entries 5–7). However, disilanes like tetra-
methyldisiloxane (TMDS) or polysilanes like polymethylhy-
drosiloxane (PMHS) were completely inactive under our re-
action conditions and only the starting ester was recovered
after the reaction. It should be noted that the observed dif-
ferences in reactivity of silanes combined with the possibility
to use different catalysts allows for a tuning of chemoselec-
tivity of multiple substituted substrates. This is not possible
with classic organometallic hydrides or in reactions with hy-
drogen. Scale up of the model reaction to 20 mmol resulted
in no problems and produced phenylethanol (1b) in 90%
yield after concomitant hydrolysis.
[7]
gioselectivity under mild conditions. Hence, during the last
decade metal-catalyzed hydrosilylations of esters have re-
ceived considerable interest. To date, various catalyst sys-
[
8]
[9]
[10]
[11]
[12]
[13]
[14]
tems including Rh, Ru, Mo, Ti, In, Mn, Pd,
[15]
[16]
organo zinc, and boron compounds have proven to be
[
a] S. Das, K. Mçller, Dr. K. Junge, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Str. 29a
1
8059 Rostock (Germany)
Fax : (+49)381-1281-51113
E-mail: matthias.beller@catalysis.de
7414
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 7414 – 7417
Das, Shoubhik
