Pd/C(en)-catalyzed regioselective hydrogenolysis of terminal epoxides to secondary alcohols

Article abstract of DOI:10.1039/a902213i

Various terminal epoxides, such as 1,2-epoxyalkanes, glycidyl ethers and glycidol, were hydrogenolyzed to give secondary alcohols with high regioselectivity using a 10% Pd/C-ethylenediamine complex as a catalyst under entirely neutral conditions.

Full text of DOI:10.1039/a902213i

Pd/C(en)-catalyzed regioselective hydrogenolysis of terminal epoxides to
secondary alcohols
Hironao Sajiki, Kazuyuki Hattori and Kosaku Hirota*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan.
E-mail: hirota@gifu-pu.ac.jp
Received (in Cambridge, UK) 19th March 1999, Accepted 28th April 1999
Various terminal epoxides, such as 1,2-epoxyalkanes, glyci-
dyl ethers and glycidol, were hydrogenolyzed to give
secondary alcohols with high regioselectivity using a 10%
Pd/C–ethylenediamine complex as a catalyst under entirely
neutral conditions.
or nucleophilic conditions (NaOH or ammonia provided from
ammonium formate) often restrict their use.7 Thus, there is a
need for the development of novel hydrogenation catalysts that
can provide high yields and selectivity as entirely heteroge-
neous catalysts under neutral conditions without any nucleo-
philic additives. We now disclose a very practical method that
overcomes these serious problems.
The reductive ring-opening reaction of epoxides, in particular
terminal epoxides, to the corresponding alcohols is a trans-
formation of considerable importance in organic synthesis1 in
connection with the recent progress in the development of
practical and efficient methods for epoxidation of terminal
olefins.2 This important transformation has mainly been
accomplished by stoichiometric metal hydride or dissolving
metal reagents,3 and such reductive cleavage with most
reducing agents generally produces a large quantity of metal
sludge. Industry in particular requires high yield, high selectiv-
ity, sufficient productivity, low cost, safety, operational sim-
plicity, and environmental consciousness among other technical
factors.2a In this context, the general advantages associated with
heterogeneous catalysts for hydrogenolysis are convenient use
and easy separation, production of no sludge and low cost. From
investigation of the hydrogenolyses of 1,2-epoxyalkanes, it was
found that while the primary alcohol is formed in greater
quantity with a Ni catalyst, the secondary alcohol is pre-
dominant with a Pd catalyst.4,5 However, the Pd catalysts have
not been practically applicable since a substantial ratio of the
reverse opening primary alcohol is obtained (ca. 35–15%) in
most cases.4,6 Some improvements were demonstrated by the
combination of Pd/C with NaOH4,7 or ammonium formate.6
Although these few reports provide successful results, the basic
Recently, we introduced a carbon-supported Pd–ethylenedi-
amine complex [Pd/C(en)] as a catalyst of choice for general
chemoselective hydrogenation of reducible functionalities such
as olefin, acetylene, nitro, azide, aromatic bromine or benzyl
ester moieties, in the presence of O-Bn or N-Z protective
groups.8 During the course of our studies aimed at developing
the Pd/C(en) complexes9 as catalysts for selective hydro-
genation,8,10 we found that 10% Pd/C(en), without any
nucleophilic additives, promotes the regioselective reductive
ring-opening of terminal epoxides to afford the corresponding
secondary alcohols with high yields and selectivity.
Hydrogenolysis of a variety of terminal epoxides in the
presence of 10% Pd/C(en) (10% of the weight of the substrate,
ca. 2 mol% as Pd metal) as catalyst in MeOH at room
temperature was carried out and the results are summarized in
Table 1. For example, 1,2-epoxydecane was hydrogenolyzed
using 10% Pd/C(en) under 5 atm of hydrogen pressure to afford
decan-2-ol as the sole product in 81% yield, whereas employ-
ment of 10% Pd/C (Aldrich) under 1 or 5 atm hydrogen pressure
resulted in the formation of a mixture of decan-2-ol and decan-
1-ol (82:18 or 84:16, Table 1, entries 1–3). The 10% Pd/C(en)-
catalyzed hydrogenolysis proceeded with complete regiose-
lectivity, although the completion of the reaction required
Table 1 Regioselective hydrogenolysis of terminal epoxides using 10% Pd/C(en) catalysta
A 10% Pd/C
B 10% Pd/C(en)
OH
O
OH
+
R
R
H2 (1–5 atm)
R
MeOH
1
2
3
Relative yield (%)c
Yield
(%)b
Entry
Substrate
Catalyst PH2/atm t/h
2
3
1
2
3
4
5
6
7
8
9
1a R = C8H17
1a R = C8H17
1a R = C8H17
1b R = Bu
1c R = HO(CH2)8
1d R = PhCH2CH2
1e R = PhOCH2
1f R = XCH2OCH2
1g R = CyCH2OCH2
1h R = HOCH2
Ad
Ad
B
B
B
B
B
B
B
1
6
3
70
72
81
75
94
95
95
99
79
89
89
82
84
18
5e
5e
5e
5e
5e
1
16
24
24
32
24
24
24
66
22
24
100
> 95
> 95
> 95
100
100
100
100
100j
NDf
g
—
g
—
g
—
NDf
NDf
NDf
NDf
NDf,j
h
1
1
1
1
10
11i
B
B
1g R = 4-ClC6H4OCH2
a Unless otherwise specified, the reaction was carried out using 0.5 mmol of the substrate in methanol (1 ml) with 10% Pd/C(en) (10% of the weight of the
substrate) under hydrogen atmosphere (1–5 atm) for the given reaction time. b Isolated yield. c Determined by 1H NMR. d 10% Pd/C was purchased from
e
f
g
h
Aldrich Co. Reaction was performed using Ishii Medium Pressure Hydrogenator CHA-E. Not detectable. Trace (less than 5%). X = 2,3-dihydro-
i
j
1,4-benzodioxan-2-yl. Reaction was performed in the presence of Et3N (1.2 equiv. vs. substrate) to neutralize the resulting HCl. Dechlorinated
product.
Chem. Commun., 1999, 1041–1042
1041

higher hydrogen pressure (5 atm). 1,2-Epoxyhexane,
1,2-epoxydecan-10-ol and 1,2-epoxy-4-phenylbutane were
similarly hydrogenolyzed (5 atm) with 10% Pd/C(en) to give
the corresponding secondary alcohols in high yields (entries
4–6). The hydrogenolysis of glycidyl ethers and glycidol gave
the corresponding secondary alcohols in high yields even under
1 atm hydrogen pressure without the formation of any
detectable by-products, such as primary alcohols (entries 7–11).
In the case of 4-chlorophenyl glycidyl ether, non-nucleophilic
Et3N (1.2 equiv.) was added to the reaction mixture as a base,
which traps HCl generated during the reaction (entry 11). In this
reaction the dechlorinated product, 1-phenoxypropan-2-ol, was
obtained in 89% yield as the sole product.
The 10% Pd/C(en) catalyst is stable and retains high
efficiency during consecutive catalytic cycles. The catalyst
could be recovered almost quantitatively following simple
filtration of the catalyst, washing with MeOH and Et2O and
drying, and it could be reused at least three times without any
decrease in the yield and regioselectivity of the hydrogenolyzed
product. One drawback of this method is the inapplicability
encountered in the hydrogenolysis of styrene oxide (1 R = Ph).
Styrene oxide was converted to a 14:86 mixture of phenethyl
alcohol (3 R = Ph) and 1-phenylethylene glycol monomethyl
ether 4, which may be formed via Pd/C(en)-catalyzed re-
gioselective solvolysis with MeOH.11
method for regioselective synthesis of secondary alcohols under
entirely neutral and heterogeneous reaction conditions.
Notes and references
1 F. A. Carey and R. J. Sundberg, Advanced Organic Chemistry, Part B,
Plenum, New York, 1977; M. Bartok and K. L. Lang, The Chemistry of
Heterocyclic Compounds—Small Ring Heterocycles, Part 3, ed. A.
Weissberger and E. C. Taylor, Wiley, New York, 1985, p. 1 and
references therein; R. Sreekumar, R. Padmakumar and P. Rugmini,
Tetrahedron Lett., 1998, 39, 5151 and references therein.
2 (a) K. Sato, M. Aoki, M. Ogawa, T. Hashimoto and R. Noyori, J. Org.
Chem., 1996, 61, 8310; (b) C. Coperet, H. Adolfsson and K. B.
Sharpless, Chem. Commun., 1997, 1565 and references therein.
3 Selected reviews: R. C. Larock, Comprehensive Organic Transforma-
tions, VCH, New York, 1989, p. 505; M. Hudlicky, Reductions in
Organic Chemistry, 2nd edn., ACS, Washington, DC, 1996, p. 113.
4 For examples: M. S. Newman, G. Underwood and M. Renoll, J. Am.
Chem. Soc., 1949, 71, 3362; P. N. Rylander, Catalytic Hydrogenation in
Organic Synthesis, Academic Press, New York, 1979, p. 260; P. N.
Rylander, Hydrogenation Methods, Academic Press, New York, 1985,
p. 137.
5 Besides the catalyst, the substrate also exerts a considerable effect on the
regioselectivity (ref. 1 and 4), see also S. Torii, H. Okuno, S. Nakayasu
and T. Kotani, Chem. Lett., 1989, 1975.
6 P. S. Dragovic, T. J. Prins and R. Zhou, J. Org. Chem.,1995, 66,
4922.
7 L. M. Schultze, H. H. Chapman, N. S. Louie, M. J. Postich, E. J. Prisbe,
J. C. Rohloff and R. H. Yu, Tetrahedron Lett., 1998, 39, 1853.
8 H. Sajiki, K. Hattori and K. Hirota, J. Org. Chem., 1998, 63, 7990.
9 The preparation of 10% Pd/C(en) catalyst: (ref. 8): A suspension of 10%
Pd/C (1.50 g, 1.40 mmol as Pd metal) and ethylenediamine (6.8 ml,
100.80 mmol) in MeOH (60 ml) under a rigorous argon atmosphere was
stirred for 48 h at ambient temperature. The solid was filtered, washed
vigorously with MeOH (20 ml 3 5) and Et2O (20 ml 3 2), and dried
under a vacuum pump at room temperature for 48 h to give the 10% Pd/
C(en) ( Found: C, 74.10; H, 2.64; N, 3.01%).
OMe
OH
Ph
4
The exact role of the ethylenediamine of the 10% Pd/C(en)
complex catalyst in facilitating the regioselective hydro-
genolysis of terminal epoxides remains unclear. The catalytic
activity of 10% Pd/C(en) to the reductive ring-opening reaction
of terminal epoxides was lower than that of 10% Pd/C. It should
be noted that higher regioselectivity was observed with the less
active catalyst.
10 H. Sajiki, K. Hattori and K. Hirota, J. Chem. Soc., Perkin Trans. 1, 1998,
4043.
11 By use of EtOH instead of MeOH as a solvent, styrene oxide could also
be converted to an 87:13 mixture of phenethyl alcohol (3 R = Ph) and
1-phenylethylene glycol monoethyl ether.
As described, the present 10% Pd/C(en)-catalyzed hydro-
genolysis of terminal epoxides would provide a new catalytic
Communication 9/02213I
1042
Chem. Commun., 1999, 1041–1042