One-pot system for reduction of epoxides using NaBH4, PdCl 2 catalyst, and moist alumina

Article abstract of DOI:10.1080/00397910903079607

Reduction of epoxides with sodium borohydride, a catalytic amount of palladium(II) chloride, and chromatographic neutral alumina preloaded with a small amount of water (moist alumina) in hexane gave alcohols in good to excellent yields and good selectivity of the desired products under mild conditions. The reaction system was operationally simple and environmentally friendly. The alumina can be recovered simply and reused a number of times without any treatment and with good activity.

Full text of DOI:10.1080/00397910903079607

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One-Pot System for Reduction of
Epoxides Using NaBH4, PdCl2 Catalyst,
and Moist Alumina
Shigetaka Yakabe a
a Nihon University, Narashino, Japan
Version of record first published: 07 Apr 2010.
To cite this article: Shigetaka Yakabe (2010): One-Pot System for Reduction of Epoxides Using NaBH4,
PdCl2 Catalyst, and Moist Alumina, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:9, 1339-1344
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Synthetic Communications1, 40: 1339–1344, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903079607
ONE-POT SYSTEM FOR REDUCTION OF
EPOXIDES USING NaBH4, PdCl2 CATALYST,
AND MOIST ALUMINA
Shigetaka Yakabe
Nihon University, Narashino, Japan
Reduction of epoxides with sodium borohydride, a catalytic amount of palladium(II)
chloride, and chromatographic neutral alumina preloaded with a small amount of water
(moist alumina) in hexane gave alcohols in good to excellent yields and good selectivity
of the desired products under mild conditions. The reaction system was operationally simple
and environmentally friendly. The alumina can be recovered simply and reused a number of
times without any treatment and with good activity.
Keywords: Epoxide; moist alumina; palladium chloride; reduction; sodium borohydride
Epoxides are widely employed as fragrance chemicals and are used in perfumes
and deodorants.[1] Epoxides can be reduced either to alcohols by ring-opening via
hydrogenolysis (Fig. 1, path A) or to alkenes by deoxygenation (Path B). Path A
enjoys an important position in organic synthesis, and therefore this process has
been the subject of extensive research.[2] It is well known that asymmetrical epoxides
afford mixtures of isomeric alcohols, the product ratios of which are strongly depen-
dent on the reducing agents employed. For example, a combination of a hydride
reagent (e.g., NaBH4 or LiAlH4) and a Lewis acid such as AlCl3,[3] zinc borohydride
supported on silica gel[4] and AlPO4,[5] and aluminumoxyhydride[6] produces the
least substituted alcohols; however, a disadvantage of these reaction methods is
the poor selectivity to the desired product. A mixture of primary and secondary
alcohols and other by-products are obtained, requiring with subsequent purification
to give the desired product in poor yields.
We have found that our system [sodium borohydride (NaBH4)=moist alumina
in hexane] is excellent for the good selective reduction of aliphatic and aromatic
carbonyl compounds to corresponding alcohols in excellent yields.[7]
Recently, this reaction system was used to develop a new one-pot reduction,
which has been applied to the synthesis of chiral alcohols, b-azidoalcohols, allylic
alcohols, 1,2-diols, and chiral lactones.[8]
Received March 25, 2009.
Address correspondence to Shigetaka Yakabe, Nihon University, Narashino 275-8575, Japan.
E-mail: shige_yakabe@yahoo.co.jp
1339

1340
S. YAKABE
Figure 1. Epoxides reduction process (Path A: ring-opening via hydrogenolysis produce alcohols, Path B:
deoxygenation produce alkene).
This reaction system was able to utilize the reduction of only various carbonyl
compounds, so we developed a new system for the reduction of alkenes that required
slightly modified reaction conditions compared with carbonyl compound reduction
conditions to produce hydrogenation products in the presence of catalytic amounts
of metal salts.[9]
In the course of our recent investigation into the synthetic utility of NaBH4
under solid–solution biphasic conditions, we found that epoxides were reduced to
alcohols by simply adding a catalytic amount of palladium(II) chloride (PdCl2) to
a heterogeneous mixture of NaBH4 and moist alumina (vide infra) in hexane. We
now report the reaction of epoxides with the NaBH4=metal catalyst=moist alumina
system because it gives a new, simple reduction of epoxides under mild conditions.
The reaction of styrene oxide (1a) with NaBH4 and moist alumina in the
presence of a variety of metal chlorides gave 2-phenylethanol (2a), along with styr-
ene (4a) and ethylbenzene (5a) in varying amounts (Fig. 2, Table 1). It should be
noted that no 1-phenylethanol (3a) was formed in any case, suggesting that regio-
selective ring opening occurred leading to the primary alcohol 2a. Of the metal
salts examined (NiCl2, CoCl2, PdCl2, BiCl3, CuCl2, CrCl2, and ZnCl2), PdCl2
may be the catalyst of choice for the present reaction in terms of the conversion
of 1a and the yield of 2a. In addition, it is frequently observed that the efficiency
of the solid–solution biphasic reactions is dependent on the solid supports
employed.[10] Therefore, another comparative study was performed using various
solid supports. Reduction activity and selectivity of products using zeolites, which
have a larger surface area and a microporous structure; clays, which have a layered
structure; montmorillonite K-10, which has strong acidity; and hydrotalcite, which
has strong basicity, are remarkably less than those of neutral alumina. Neutral
alumina was superior to the others as a support.
Reduction of typical aryl, aliphatic, and alicyclic epoxides was carried out
with the NaBH4=PdCl2 catalyst=moist alumina system in hexane (Fig. 3). Table 2
Figure 2. Styrene oxidation reduction.

ONE-POT SYSTEM FOR REDUCTION OF EPOXIDES
1341
Table 1. Effect of metal salts on the reduction of styrene oxidea
GC yield (%)
Entry
Metal salt
1ab
2a
3a
4a
5a
1
2
3
4
5
6
7
8
NiCl2 Á 6H2O
CoCl2 Á 6H2O
PdCl2
38
80
54
11
69
11
14
2
0
0
0
0
0
0
0
0
trace
6
trace
24
1
9
0
0
63
BiCl3
8
CuCl2 Á 2H2O
CrCl2
ZnCl2
56
85
27
0
3
0
87
>99
2
0
0
—
0
0
0
aAt 40 ꢀC for 3 h; 1a (1 mmol), NaBH4 (2 mmol), moist alumina (H2O content, 19
wt.%, 2 g), metal salt (0.1 mmol), and hexane (10 ml) were used.
bRecovered substrate in mol%.
summarizes the optimized yields of alcohols, in which only alcoholic products (2 and
3) are presented, because alkenes were (if any) formed in negligible or only minor
amounts. Aryl epoxides (entries 1–7) underwent smooth reduction to give exclusively
the alcohols 2. Reductive dechlorination accompanied the reaction of p-chlorostyr-
ene oxide (1e), giving 2-phenylethanol in 20% yield. Chloro-substituted aromatic and
aliphatic compounds converted to dechlorination compounds using the
palladium-supported catalyst; therefore cleavage of the C-Cl bond also occurred
in this reaction system.[11]
In the case of p-nitrostyrene oxide (1f), the nitro-moiety was susceptible to the
reduction and afforded 2-(4-aminophenyl)ethanol and 4-aminophenylethane in 54%
and 5%, respectively. Aliphatic (entries 8–10) and alicyclic (entries 11 and 12)
epoxides were less reactive toward the present reducing system than the aromatic
Figure 3. Epoxides reduction and structure of epoxides.

1342
S. YAKABE
Table 2. Reduction of epoxidesa
Alcohold
2
Entry Epoxide NaBH4 (mmol) Al2O3 (g) PdCl2 (mmol) Temp. (ꢀC) Time (h) 1c
3
b
1e
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
0.5
0.5
2.0
0.5
1.0
2.0
0.5
4.0
4.0
5.0
4.0
4.0
0.5
0.5
2.0
0.5
1.5
2.0
0.5
4.0
3.0
4.0
3.0
4.0
0.1
0.1
0.2
0.1
0.1
0.2
0.1
0.4
0.3
0.4
0.3
0.3
30
30
60
30
30
60
30
60
60
60
60
60
1
1
3
1
1
3
2
6
4
3
4
4
0
0
84
93
0
0
0
33 65
0
>99
0
0
0
70f
54g
84
2
0
0
1g
1h
1i
0
0
91
25
25
89
90
2
75
3
10
1j
53 13
11
12
1k
1l
8
4
aEpoxide (1 mmol) and hexane (10 ml) were used.
bMoist alumina (H2O content, 19 wt.%) was used.
cIsolated yield (mol%).
dRecovered epoxide in mol%.
eEthylbenzene (14%) was formed.
f2-Phenylethanol (20%) was formed.
g2-(4-Amino-phenyl)ethanol; 4-aminophenylethane (5%) was also formed (see text).
epoxides, and appreciable amounts of the starting materials were recovered. The
observed high reactivity of the aromatic substrates as well as the exclusive formation
of the alcohols 2 could be responsible for the stability of the intermediate benzylic
cations, because in the case of asymmetrical epoxides it is generally accepted that
reducing agents preferentially attack carbons, generating more stabilized cations
en route to the major products.[12] However, allylbenzene oxide (1c) and 1-decene
oxide (1i) gave the secondary alcohols 3c and 3i, respectively, in preference to the
corresponding primary alcohols 2. These results cannot reasonably be explained only
by the relative stabilities of the intermediate carbocations.[13] Alternative factors such
as geometry of the substrates and=or intermediates (i.e., restriction or steric control)
on the alumina surface may play a role in determining the observed product distribu-
tions. In the absence of moist alumina, no appreciable conversion of 1a, for example,
was observed; therefore, the present reaction certainly took place on the alumina
surface. Thus, further studies of the detailed mechanism is currently under way in
our laboratory.
The alumina can be recovered by simple filtration (see the Experimental
section) and reused a few times with good activity and without any treatment. The
alumina might be reused a number of times based on the yield and selectivity of
the desired product.
In summary, the reduction of various epoxides with the NaBH4=PdCl2 catalyst=
moist alumina system in hexane gave the least substituted alcohols in good to excel-
lent yields under mild conditions. This system requires no preparation of the reducing
agents, which introduces an additional stage. We are now looking for an alternative
synthetic target using the NaBH4-based heterogeneous system.

ONE-POT SYSTEM FOR REDUCTION OF EPOXIDES
1343
EXPERIMENTAL
A typical experiment was carried out as follows: deionized water (0.095 g) was
added to chromatographic neutral alumina (ICN Biomedical, Alumina N, Super I;
0.41 g) in several portions, followed by vigorous shaking of the mixture on every
addition for a few minutes until a free-flowing powder was obtained, to afford moist
alumina (H2O content, 19 wt.%), which was immediately used for the reduction.
Styrene oxide 1a (0.12 g, 1 mmol), hexane (10 mL), PdCl2 (Wako; 0.017 g, 0.1 mmol),
freshly prepared moist alumina (0.50 g), and NaBH4 (Wako; 0.019 g, 0.5 mmol) were
placed into a 30-mL round-bottom flask, and the resultant heterogeneous mixture
was magnetically stirred at 30 ꢀC. After 1 h, the reaction mixture was filtered, and
the filter cake was washed thoroughly with portions of dry ether (in total, ca.
60 mL). The yield of 2a was determined by gas chromatography (GC) using anisole
as an internal standard. The alcohols listed in Table 2 were isolated.
Alcohols thus obtained were identified spectroscopically (1H NMR, IR,
GC-MS) via comparisons with the authentic samples.
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