Highly chemoselective hydrogenation with retention of the epoxide function using a heterogeneous Pd/C - Ethylenediamine catalyst and THF

Article abstract of DOI:10.1002/1521-3765(20000616)6:12<2200::AID-CHEM2200>3.0.CO;2-3

In general, palladium-carbon (Pd/C) catalyzed hydrogenation of epoxides affords the corresponding primary and secondary alcohols as a mixture. It has been found that the catalytic activity of a Pd/C - ethylenediamine complex catalyst [Pd/C(en)] in the hydrogenolysis of epoxide functions is drastically reduced. Herein we describe a mild and chemoselective method for the hydrogenation of olefin, nitro, and azide functions with retention of the epoxide function. The chemoselectivity was accomplished by using a combination of 5% Pd/C(en) and THF as solvent. A significant drop in the chemoselectivity of the hydrogenation is observed with 5% Pd/C(en) in MeOH. These results reinforce the utility of epoxides as important precursors of alcohols in synthetic chemistry.

Full text of DOI:10.1002/1521-3765(20000616)6:12<2200::AID-CHEM2200>3.0.CO;2-3

FULL PAPER
Highly Chemoselective Hydrogenation with Retention of the Epoxide
Function Using a Heterogeneous Pd/C ± Ethylenediamine Catalyst and THF
Hironao Sajiki,* Kazuyuki Hattori, and Kosaku Hirota*[a]
Abstract: In general, palladium ± car-
bon (Pd/C) catalyzed hydrogenation of
epoxides affords the corresponding pri-
mary and secondary alcohols as a mix-
ture. It has been found that the catalytic
a mild and chemoselective method for
the hydrogenation of olefin, nitro, and
azide functions with retention of the
epoxide function. The chemoselectivity
was accomplished by using a combina-
tion of 5% Pd/C(en) and THF as
solvent. A significant drop in the chemo-
selectivity of the hydrogenation is ob-
served with 5% Pd/C(en) in MeOH.
These results reinforce the utility of
epoxides as important precursors of
alcohols in synthetic chemistry.
activity of
a Pd/C ± ethylenediamine
Keywords: chemoselectivity ´ epox-
complex catalyst [Pd/C(en)] in the hy-
drogenolysis of epoxide functions is
drastically reduced. Herein we describe
ides
´ heterogeneous catalysis ´
hydrogenations
hydrogenated a variety of reducible functionalities with
retention of O-benzyl and N-Cbz protective groups and
benzyl alcohol grous under mild conditions.[8]
Introduction
Manipulation of functional groups is a fundamental process in
synthetic organic chemistry and, hence, the development of
new chemoselective transformations remains of great inter-
est.[1] The highly strained epoxy function is easily ring-opened
under reductive conditions.[2] Consequently, it is extremely
difficult to keep the epoxide function intact during synthetic
processes involving reduction steps, such as hydrogenation,
and hydride reduction, though epoxides are important and
widely used intermediates in organic synthesis as precursors
of alcohols. Among the very few examples of chemoselective
catalytic hydrogenations that distinguish the epoxide func-
tion, their functionality is intrinsically specific and applicable
to only the following functions: acetylene (Lindlar catalyst),[3]
olefin with sterically hindered epoxide (Pt),[4] epoxy conju-
gated olefin ([{(tBu2Ph)PdPtBu2}2] or [Ir(COD)(PPh3)-
(PhCN)]BF4)[5], and a,b-unsaturated ester (Mg/MeOH).[6]
We recently found that a system comprising palladium/
carbon (Pd/C) and added amine is an excellent catalyst for the
chemoselective hydrogenation of many reducible function-
alities in the presence of an O-benzyl protective group.[7] In
addition, Pd/C formed an isolable complex with ethylenedi-
amine, and its complex catalyst [Pd/C(en)] chemoselectively
Results and Discussion
During our efforts to extend the applicability of Pd/C(en), we
observed that Pd/C(en) shows very low catalytic activity
towards the hydrogenolysis of epoxides, compared with Pd/C.
The hydrogenation of epoxydecane (2b) catalyzed by 5% Pd/
C(en) resulted in very poor conversion to the alcohol (3b,
19%),[9] and 81% of the unchanged epoxide (2b) remained
even after hydrogenation in MeOH for 48 h at ordinary
pressure (balloon)(Table 1). On the other hand, the use of 5%
Pd/C as catalyst resulted in the hydrogenation of 2b to give
the corresponding alcohols (3b and 4b) within only 6 h.
Further fine-tuning of reaction conditions indicated that THF
is a highly effective solvent for 5% Pd/C(en)-catalyzed
chemoselective hydrogenation in the presence of an epoxy
function.
To explore the scope of this method, the hydrogenation of a
number of substrates (1) was investigated (Table 2). The
results shown in entries 1 ± 9 demonstrated that the chemo-
selective hydrogenation could be accomplished by employing
À
epoxy compounds with terminal and internal C C double
[a] Assoc. Prof. Dr. H. Sajiki, Prof. Dr. K. Hirota, K. Hattori
Laboratory of Medicinal Chemistry
Gifu Pharmaceutical University
bonds. The hydrogenation almost entirely tolerates epoxides.
Although the resulting products were contaminated by trace
amounts of over-reduction products (3 and 4) in some cases
(entries 1, 2, 3, and 8), the alcoholic contaminants (3 and 4)
could be removed easily by simple flash column chromatog-
raphy.[10] Nitro and azide moieties were also successfully
Mitahora-higashi, Gifu 502 ± 8585 (Japan)
Fax : (‡81)58 ± 237 ± 5979
E-mail: sajiki@gifu-pu.ac.jp
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/chemistry/ or from the author.
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Chem. Eur. J. 2000, 6, No. 12

2200±2204
Table 1. Influence of catalysts and solvents.[a]
Although purification of gly-
cidyl 4-aminobenzoate (2k),
3-aminobenzyl glycidyl ether
(2l), and 4-aminophenyl gly-
cidyl ether (2m) from the re-
action mixture has proved to be
difficult by column chromatog-
raphy because of their lability
on silica gel (entries 11 ± 13),
the selectivity (93 ± 95%) of
the formation of the desired
amino epoxides (2k ± m) is suf-
ficiently high for the direct use
of the crude products in the
Relative yield [%][b]
Catalyst
Solvent
t [h]
2b
3b
4b
5% Pd/C
5% Pd/C(en)
5% Pd/C(en)
MeOH
MeOH
THF
6
48
48
0
81
100
82
19
0
18
0
0
[a] The hydrogenation was carried out using 1 mmol of the substrate in MeOH (1 mL) or THF (1 mL) with
catalyst (10% of the weight of the substrate). [b] Determined by H NMR spectroscopy.
1
transformed into an amino group without ring cleavage of the
epoxy function under these conditions (entries 10 ± 14).
following reactions. The catalyst could be recovered almost
quantitatively after simple filtration and it could be reused.
Table 2. 5% Pd/C(en)-THF catalyzed hydrogenation.[a]
Entry
Substrate 1
t [h]
Major product 2
Yield of 2 [%]
Product ratio
2
3
4
[b]
1
2
3
1a
1b
1c
3
96
97
98
0
0
2
4
3
0
3
85
[b]
2.5
4
5
1d
1e
3
3
92
94
100
100
0
0
0
0
6
1 f
3
98
100
0
0
0
7
8
1g
1h
9
87
93
100
97
0
24[c]
(3)
9
1i
1j
12[c]
18
86
100
100
0
0
0
0
10
100
11
1k
8
99[d]
96
4
0
12
13
1l
14
3
100[d]
94[d]
93
95
7
5
0
0
1m
14
1n
19
97
100
0
0
[a] Unless otherwise specified, the reaction was carried out using 0.5 mmol of the substrate in THF (1 mL) with 5% Pd/C(en) (10% of the weight of the
substrate) under a hydrogen atmosphere (balloon) for the given reaction time. [b] Because of the low boiling point of the products, the quantitative
conversion was observed by NMR spectroscopy in [D8]THF. [c] Reaction was performed under 5 atm of hydrogen using Ishii medium-pressure hydrogenator
CHA-E. [d] The yield was indicated as a crude mixture since the isolation of the product (2k, 2l, or 2m) from the reaction mixture by column
chromatography was difficult because of their lability on silica gel.
Chem. Eur. J. 2000, 6, No. 12
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2201

H. Sajiki, K. Hirota, and K. Hattori
FULL PAPER
distilled from sodium benzophenone ketyl immediately prior to use.
Medium-pressure (5 atm) hydrogenation was performed using an Ishii
hydrogenator CHA-E. 1,2-Epoxy-7-octene (1a), 1,2-epoxy-9-decene (1b),
allyl glycidyl ether (1c), glycidyl methacryrate (1e), 9,10-epoxy-1,5-cyclo-
dodecadiene (1h), and 1,2-epoxy-3-(4-nitrophenoxy)propane (1m) were
purchased from Tokyo Kasei Kogyo Co. (TCI), Kanto Chemical Co., Wako
Pure Chemical Industries or Acros Organics and used without further
purification. 2,3-Epoxygeraniol (1i) was prepared according to the
previously outlined procedure.[14]
The recovered 5% Pd/C(en) was also effective in the second
and third reactions, and the yields and selectivity of the second
and third runs were comparable to those of the first run. A
limitation of this methodology is that epoxides derived from
styrene derivatives would be easily converted into primary
alcohols with the ring-cleavage of the epoxide (e. g., phe-
nethyl alcohol).[11]
At present, detailed mechanistic studies have not been
undertaken and the exact process that leads to the chemo-
selectivity is unclear. It is likely that a large excess of THF
oxygen atoms occupies the surface of the palladium of 5% Pd/
C(en) instead of the epoxide oxygen atoms. This process
results in a blocking of the hydrogenolysis of epoxides. It may
be noted that the hydrogenation of the unsaturated terminal
epoxide 1a or 1b gave a small amount of a saturated primary
alcohol (4a or 4b) as a by-product together with the desired
saturated epoxide (2a or 2b) (Table 1, entries 1 and 2), while
the hydrogenolysis of the saturated terminal epoxide 2b using
5% Pd/C(en) in MeOH only gave the corresponding secon-
dary alcohol (2-decanol, 3b) together with unchanged 2b
(Table 1).[9] These observations would be explained by the
continuous isomerization of the olefin moiety during the
catalysis [Eq. (1), see also Supporting Information].[12, 13] The
competition between the hydrogenation and the isomeriza-
Glycidyl 5-hexenyl ether (1d): 5-Hexene-1-ol (1.00 g, 10.00 mmol) was
added to a solution of epichlorohydrin (5 mL) and tetrabutylammmonium
hydrogensulfate (0.34 g, 1.00 mmol) in 50% NaOH aqueous solution
(5 mL). The mixture was stirred at room temperature (RT) for 9 h. The
reaction mixture was poured into water (15 mL) and extracted with Et2O
(15 mL). The ethereal layer was washed with water (15 mL) and brine
(15 mL) and dried over anhydrous magnesium sulfate. The solvent was
evaporated to dryness. Flash column chromatography (hexane/ Et2O 50:1)
yielded 1d (1.18 g, 75%) as a colorless oil. 1H NMR (400 MHz, RT,
CDCl3): d ˆ 1.42 ± 1.64 (m, 4H), 2.07 (q, J ˆ 7.2 Hz, 2H), 2.61 (dd, J ˆ 2.9
and 4.6 Hz, 1H), 2.79 (t, J ˆ 4.6 Hz, 1H), 3.12 ± 3.16 (m, 1H), 3.38 (dd, J ˆ
5.6 and 11.6 Hz, 1H), 3.44 ± 3.55 (m, 2H), 3.70 (dd, J ˆ 2.9 and 11.6 Hz, 1H),
4.94 ± 5.03 (m, 1H), 5.76 ± 5.86 (m, 1H); 13C NMR (100 MHz, RT, CDCl3):
d ˆ 25.25, 28.99, 33.35, 44.08, 50.72, 71.28, 71.31, 114.38, 138.50; elemental
analysis calcd (%) for C9H16O2 ´ 1/5H2O: C 67.63, H 10.34; found: C 67.59,
H 10.05. The existence of water in this product was confirmed by 1H NMR
analysis.
Cinnamyl glycidyl ether (1 f): Preparation of 1 f was performed analogously
to the procedure described for 1d with cinnamyl alcohol (3.83 mL,
29.60 mmol). Yield: 84% (4.75 g);
1H NMR (400 MHz, RT, CDCl3): d ˆ
2.64 (dd, J ˆ 2.7 and 4.8 Hz, 1H), 2.82
(t, J ˆ 4.8 Hz, 1H), 3.18 ± 3.22 (m, 1H),
3.45 (dd, J ˆ 5.9 and 11.6 Hz, 1H), 3.78
(dd, J ˆ 3.2 and 11.6 Hz, 1H) 4.17 ±
4.27 (m, 2H), 6.26 ± 6.33 (m, 1H),
6.62 (d, J ˆ 16.1 Hz, 1H), 7.23 ± 7.41
(m, 5H); 13C NMR (100 MHz, RT,
tion characterizes the product ratio. In addition, by replacing
a methylene moiety between the epoxide and olefin functions
of 1a or 1b with an oxygen atom to inhibit the isomerization,
the formation of the corresponding saturated primary alcohol
(4) as a by-product was not observed under the same
conditions (Table 1, entries 3, 4, 6 and 7).
CDCl3): d ˆ 44.23, 50.74, 70.67, 71.79, 125.54, 126.41, 127.66, 128.46, 132.69,
‡
136.51; HRMS (EI) calcd for C12H14O2 [M ] 190.0994, found 190.0998.
1-(Glycidoxymethyl)-3-cyclohexene (1g): Preparation of 1g was per-
formed analogously to the procedure described for 1d with 3-cyclo-
1
hexene-1-methanol (2.00 mL, 17.00 mmol). Yield: 53% (1.50 g); H NMR
(400 MHz, RT, CDCl3): d ˆ 1.23 ± 1.33 (m, 1H), 1.69 ± 1.84 (m, 2H), 1.88 ±
1.96 (m, 1H), 2.04 ± 2.14 (m, 3H), 2.61 (dd, J ˆ 2.9 and 4.4 Hz, 1H), 2.79
(dd, J ˆ 4.4 and 5.1 Hz, 1H), 3.13 ± 3.17 (m, 1H), 3.35 ± 3.44 (m, 3H), 3.72
(dd, J ˆ 1.5 and 3.2 Hz, 1H), 5.63 ± 5.70 (m, 2H); 13C NMR (100 MHz, RT,
CDCl3): d ˆ 24.24, 25.26, 28.13, 33.64, 43.68, 43.79, 50.50, 50.56, 71.37, 76.07,
76.10, 125.61, 126.69; elemental analysis calcd (%) for C10H16O2 ´ 1/10H2O:
C 70.64, H 9.60; found: C 70.68, H 9.65. The existence of water in this
Conclusion
1
product was confirmed by H NMR analysis.
We have developed a mild and chemoselective hydrogenation
method using a 5% Pd/C(en)-THF system, which is widely
applicable to the selective hydrogenation of a variety of
olefins and nitro and azide groups leaving intact the epoxide
functions. These findings reinforce the utility of epoxides as
important precursors of alcohols.
Glycidyl 3-nitrobenzyl ether (1l): Preparation of 1l was performed
analogously to the procedure described for 1d with 3-nitrobenzyl alcohol
(0.77 g, 5.00 mmol). Yield: 90% (0.94 g); 1H NMR (270 MHz, RT, CDCl3):
d ˆ 2.65 (dd, J ˆ 2.5 and 4.8 Hz, 1H), 2.84 (t, J ˆ 4.8 Hz, 1H), 3.20 ± 3.26 (m,
1H), 3.46 (dd, J ˆ 6.1 and 11.5 Hz, 1H), 3.90 (dd, J ˆ 2.7 and 11.5 Hz, 1H),
4.65 and 4.72 (d, J ˆ 12.5 Hz, each 1H), 7.53 (t, J ˆ 8.1 Hz, 1H), 7.69 (d, J ˆ
8.1 Hz, 1H), 8.16 (d, J ˆ 8.1 Hz, 1H), 8.23 (s, 1H); 13C NMR (100 MHz, RT,
CDCl3): d ˆ 43.31, 50.10, 70.97, 71.13, 121.37, 121.79, 128.79, 132.80, 139.98,
‡
147.67; MS (FAB: NBA): m/z (%): 210 (5) [M ‡H].
1,2-Epoxypentyl 4-nitrobenzoate (1j): 4-Nitrobenzoyl chloride (1.85 g,
10.00 mmol) was added to a solution of 4-penten-1-ol (1.03 g, 12.00 mmol),
triethylamine (2.09 mL, 15.00 mmol), and 4-(dimethylamino)pyridine
(DMAP) (0.12 g, 1.00 mmol) in THF (10 mL). The mixture was stirred at
room temperature for 3 h. The reaction mixture was poured into water
(50 mL) and extracted with ethyl acetate (50 mL). The organic layer was
washed with water (30 mL), saturated aqueous NaHCO3 (30 mL), water
(30 mL), 10% NaHSO4 solution (30 mL), water (30 mL), and brine
(30 mL), and dried over anhydrous magnesium sulfate. The solvents were
evaporated to dryness. Flash column chromatography (hexane/Et2O 100:1)
yielded 4-pentenyl 4-nitrobenzoate (1.09 g, 47%) as a yellow oil. 1H NMR
Experimental Section
General: H NMR and 13C NMR spectroscopy: JEOL JNM GX-270 and
1
JEOL JNM EX-400 (1H NMR: 270 MHz and 400 MHz; 13C NMR:
100 MHz); MS: JMS-SX 102A; TLC (thin-layer chromatography):
0.25 mm silica gel 60 F254 plates (Art 5715, Merck) using UV light as a
visualizing agent and 7% ethanolic phosphomolybdic acid or p-anisalde-
hyde solution, and heat as developing agent; column chromatography:
silica gel 60 (230 ± 400 mesh, Merck). Melting points were determined on a
Yanagimoto melting point apparatus and were uncorrected. THF was
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Chemoselective Hydrogenation
2200±2204
(270 MHz, RT, CDCl3): d ˆ 1.91 (p, J ˆ 6.2 Hz, 2H), 2.24 (q, J ˆ 6.2 Hz,
2H), 4.40 (t, J ˆ 6.2 Hz, 2H), 5.02 ± 5.13 (m, 2H), 5.78 ± 5.93 (m, 1H);
13C NMR (100 MHz, RT, CDCl3): d ˆ 27.70, 30.00, 65.26, 115.49, 123.45,
130.58, 135.70, 137.09, 150.46, 164.60; HRMS (FAB) calcd for C12H14O4N
4.9 Hz, 1H), 2.87 ± 2.94 (m, 1H), 3.26 (t, J ˆ 6.8 Hz, 2H); 13C NMR
(100 MHz, RT, CDCl3): d ˆ 25.65, 26.40, 28.56, 28.76, 29.03, 29.09, 32.18,
‡
46.64, 51.16, 51.93; HRMS (FAB) calcd for C10H20ON3 [M ‡H] 198.1606,
found 198.1611.
‡
[M ‡H] 236.0923, found 236.0918.
General procedure for 5% Pd/C(en)-THF catalyzed hydrogenation
(Table 2): Unless otherwise specified, the reaction was carried out as
follows. After two vacuum/H2 cycles to remove air from the reaction tube,
the stirred mixture of the substrate 1 (0.5 mmol) and 5% Pd/C(en) (10% of
the weight of 1) in THF (1 mL) was hydrogenated at ambient pressure
(balloon) and temperature (ca. 208C) for the appropriate time (see
Table 2). The reaction mixture was filtered by using a celite cake or a
membrane filter (Millipore Dimex-13, 0.22 mm) and the filtrate was
concentrated in vacuo. The quantitative conversion of 1 and the product
4-Pentenyl 4-nitrobenzoate (1.00 g, 4.25 mmol) in CH2Cl2 (20 mL) was
added to a solution of 70% m-chloroperbenzoic acid (1.15 g, 4.68 mmol) in
CH2Cl2 (30 mL) at such a rate as to keep the temperature about 258C for
10 min. The mixture was stirred at room temperature for 7 h. The reaction
mixture was poured into water (50 mL) and extracted with CHCl3
(100 mL). The organic layer was washed with water (30 mL) and brine
(30 mL) and dried over anhydrous magnesium sulfate. The solvents were
evaporated to dryness. Flash column chromatography (hexane/Et2O 2:1)
1
1
ratio of 2, 3, and 4 were confirmed by H NMR spectroscopy of the crude
yielded 1j (0.91 g, 86%) as a yellow oil. H NMR (270 MHz, RT, CDCl3):
mixture in CDCl3. The crude mixture was purified by flash silica gel column
chromatography, if necessary.
d ˆ 1.62 ± 1.77 (m, 1H), 1.78 ± 1.86 (m, 1H), 1.86 ± 2.07 (m, 2H), 2.53 (dd,
J ˆ 2.7 and 4.8 Hz, 1H), 2.80 (t, J ˆ 4.8 Hz, 1H), 2.97 ± 3.03 (m, 1H), 4.44 (t,
J ˆ 6.3 Hz, 2H), 8.21 and 8.30 (each d, J ˆ 9.3 Hz, 2H); 13C NMR
(100 MHz, RT, CDCl3): d ˆ 24.62, 28.45, 46.11, 50.94, 64.82, 122.85,
1,2-Epoxyoctane (2a) and 1-octanol (4a): Because of the low boiling point
of the products(2a and 4a), the reaction was carried out using [D8]THFas a
solvent and the quantitative conversion of 1a and the ratio of 2a and 4a
‡
130.00, 135.05, 149.86, 163.81; HRMS (FAB) calcd for C12H14O5N [M ‡H]
1
252.0872, found 252.0866.
(96:4) were confirmed by H NMR spectroscopy of the reaction mixture.
The products (2a and 4a) were identical with the samples commercially
purchased (TCI).
Glycidyl 4-nitrobenzoate (1k): 4-Nitrobenzoyl chloride (1.85 g,
10.00 mmol) was added to a solution of glycidol (0.80 mL, 12.00 mmol),
triethylamine (2.09 mL, 15.00 mmol), and 4-(dimethylamino)pyridine
(0.12 g, 1.00 mmol) in THF (10 mL). The mixture was stirred at room
temperature for 15 h. The reaction mixture was poured into water (50 mL)
and extracted with ethyl acetate (50 mL). The organic layer was washed
with water (30 mL), saturated aqueous NaHCO3 (30 mL), water (30 mL),
10% NaHSO4 solution (30 mL), water (30 mL), and brine (30 mL) and
dried over anhydrous magnesium sulfate. After filtration, the solvents were
evaporated to afford 1k (423 mg, 19%) as a white solid. M. p. 55 ± 568C;
1H NMR (400 MHz, RT, CDCl3): d ˆ 2.75 (dd, J ˆ 2.4 and 4.4 Hz, 1H), 2.93
(t, J ˆ 4.4 Hz, 1H), 3.36 ± 3.39 (m, 1H), 4.20 (dd, J ˆ 6.8 and 12.2 Hz, 1H),
4.74 (dd, J ˆ 2.9 and 12.2 Hz, 1H), 8.25 and 8.31 (each d, J ˆ 9.3 Hz, 2H);
13C NMR (100 MHz, RT, CDCl3): d ˆ 44.67, 49.17, 66.43, 123.60, 130.90,
1,2-Epoxydecane (2b) and 1-decanol (4b): The products (2b and 4b) were
obtained from 1b as a crude mixture (2b:4b ˆ 97:3), which were identical
with the samples commercially purchased (TCI). The product 2b was
isolated by flash silica gel column chromatography (hexane/Et2O 5:1) in
85% yield as a colorless oil.
Glycidyl propyl ether (2c)[15] and 1-propoxy-2-propanol (3c): Because of
the low boiling point of the products, the reaction was carried out using
[D8]THF as a solvent, and the quantitative conversion of 1c was confirmed
by 1H NMR spectroscopy of the reaction mixture. The product ratio of 2c
and 3c (98:2) was determined on the basis of the integration ratio of the
epoxide-ring protons of 2c (d ˆ 2.63, 2.81 and 3.15 ± 3.19) and the methyl
proton (3-position) of 3c (d ˆ 1.22, d. J ˆ 6.4 Hz). The product 3c was
identical with the sample commercially purchased (Aldrich). 2c: 1H NMR
(400 MHz, RT, [D8]THF): d ˆ 1.09 (t, J ˆ 7.3 Hz, 3H), 1.73 (m, 2H), 2.63
(dd, J ˆ 2.4 and 5.4 Hz, 1H), 2.81 (dd, J ˆ 3.9 and 5.4 Hz, 1H), 3.15 ± 3.19
(m, 1H), 3.46 (dd, J ˆ 5.8 and 11.6 Hz, 1H), 3.52 ± 3.63 (m, 2H), 3.78 (dd,
J ˆ 3.2 and 11.6 Hz, 1H); 13C NMR (100 MHz, RT, CDCl3): d ˆ 10.45, 22.87,
44.32, 50.89, 71.40, 73.27.
‡
135.03, 150.76, 164.40; MS (FAB: NBA) m/z (%) 224 (40) [M ‡H];
elemental analysis calcd (%) for C10H9O5N: C 53.82, H 4.06, N 6.28; found:
C 53.72, H 4.03, N 6.36.
1-Azido-9,10-epoxydecane (1n): Methanesulfonyl chloride (0.85 mL,
11.00 mmol) was added dropwise to
a
cooled (À108C) solution of
9-decen-1-ol (1.56 g, 20.00 mmol) and triethylamine (1.50 mL, 11.00 mmol)
in CH2Cl2 (50 mL) under an Ar atmosphere. The reaction mixture was
stirred at room temperature for 12 h and quenched with ice water (30 mL).
The organic layer was washed with 5% KHSO4 solution (30 mL), water
(30 mL), 5% Na2CO3 solution (30 mL), and brine (30 mL), then dried over
anhydrous magnesium sulfate. After filtration, the solvent was evaporated
to afford a pale yellow oil that was used in the next reaction without further
purification (1.98 g, 85%). 1H NMR (270 MHz, RT, CDCl3): d ˆ 1.31 ± 1.43
(m, 10H), 1.75 (pen, J ˆ 6.6 Hz, 2H), 2.04 (q, J ˆ 7.0 Hz, 2H), 2.96 (s, 3H),
4.22 (t, J ˆ 6.6 Hz, 2H), 4.91 ± 5.03 (m, 2H), 5.73 ± 5.88 (m, 1H); MS (FAB:
Glycidyl hexyl ether (2d): The product 2d was afforded as the sole product
1
in 92% yield from 1d as a colorless oil. H NMR (400 MHz, RT, CDCl3):
d ˆ 0.89 (t, J ˆ 6.8 Hz, 3H), 1.29 ± 1.36 (m, 4H), 1.55 ± 1.60 (m,4H), 2.61 (dd,
J ˆ 2.7 and 4.8 Hz, 1H), 2.80 (t, J ˆ 4.8 Hz, 1H), 3.13 ± 3.17 (m, 1H), 3.38
(dd, J ˆ 5.9 and 11.4 Hz, 1H), 3.43 ± 3.54 (m, 2H), 3.70 (dd, J ˆ 3.2 and
11.4 Hz, 1H); 13C NMR (100 MHz, RT, CDCl3): d ˆ 14.02, 22.59, 25.74,
29.65, 31.66, 44.34, 50.90, 71.46, 71.73; elemental analysis calcd (%) for
C9H18O2 ´ 1/4H2O: C 66.42, H 11.46; found: C 66.30, H 11.23(volatile). The
existence of water in this product was confirmed by 1H NMR analysis.
‡
NBA): m/z (%): 235 (32%) [M ‡H].
Glycidyl isobutyrate (2e): The product 2e was afforded as the sole product
in 94% yield from 1e as a colorless oil . 1H NMR (270 MHz, RT, CDCl3):
d ˆ 1.19 (d, J ˆ 6.8 Hz, 6H), 2.61 (m, 1H), 2.65 (dd, J ˆ 2.7 and 4.8 Hz, 1H),
2.84 (t, J ˆ 4.8 Hz, 1H), 3.18 ± 3.24 (m, 1H), 3.93 (dd, J ˆ 6.3 and 12.4 Hz,
1H), 4.41 (dd, J ˆ 3.2 and 12.4 Hz, 1H); 13C NMR (100 MHz, RT, CDCl3):
d ˆ 18.83, 33.77, 44.45, 49.31, 64.58, 176.69; elemental analysis calcd (%) for
C7H12O3 ´ 1/2H2O: C 54.89, H 8.55; found: C 55.07, H 8.12(volatile). The
existence of water in this product was confirmed by 1H NMR analysis.
To a solution of the above mesylate (2.27 g, 9.70 mmol) in anhydrous DMF
(15 mL) was added NaN3 (0.95 g, 14.55 mmol). The reaction mixture was
stirred at 508C for 22 h. The solvent was evaporated and the residue was
partitioned between ethyl acetate (50 mL) and water (50 mL). The organic
layer was washed with water (50 mL) and brine (50 mL) and dried over
anhydrous magnesium sulfate. After filtration, the solvent was evaporated
to afford 1-azido-9-decene as a colorless oil, which was used in the next
reaction without further purification (1.60 g, 91%). 1H NMR (270 MHz,
RT, CDCl3): d ˆ 1.31 ± 1.52 (m, 10H), 1.52 ± 1.65 (m, 2H), 2.04 (q, J ˆ
7.0 Hz, 2H), 3.26 (t, J ˆ 6.8 Hz, 2H), 4.91 ± 5.04 (m, 2H), 5.74 ± 5.89 (m,
1H).
1-Glycidoxy-3-phenylpropane (2 f): The product 2 f was afforded as the
1
sole product in 98% yield from 1 f as a colorless oil. H NMR (400 MHz,
RT, CDCl3): d ˆ 1.88 ± 1.95 (m, 2H), 2.61 (dd, J ˆ 2.7 and 5.1 Hz, 1H), 2.70
(t, J ˆ 7.8 Hz, 2H), 2.80 (dd, J ˆ 4.2 and 5.1 Hz, 1H), 3.13 ± 3.17 (m, 1H),
3.38 (dd, J ˆ 5.9 and 11.4 Hz, 1H), 3.45 ± 3.56 (m, 2H), 3.71 (dd, J ˆ 3.2 and
11.4 Hz, 1H), 7.16 ± 7.20 (m, 3H), 7.25 ± 7.30 (m, 2H); 13C NMR (100 MHz,
RT, CDCl3): d ˆ 31.21, 32.21, 44.28, 50.83, 70.64, 71.48, 125.76, 128.30,
1-Azido-9-decene (0.91 g, 5.00 mmol) in CH2Cl2 (10 mL) was added to a
solution of 70% m-chloroperbenzoic acid (1.36 g, 5.50 mmol) in CH2Cl2
(10 mL) at such a rate as to keep the temperature at about 258C for 10 min.
The mixture was stirred at RT for 7 h. The reaction mixture was poured into
water (20 mL) and extracted with CHCl3 (50 mL). The organic layer was
washed with water (20 mL) and brine (20 mL) and dried over anhydrous
magnesium sulfate. After filtration, the solvent was evaporated to afford 1n
(0.96 g, 98%) as a pale yellow oil. 1H NMR (270 MHz, RT, CDCl3): d ˆ
1.33 ± 1.63 (m, 14H), 2.46 (dd, J ˆ 2.9 and 4.9 Hz, 1H), 2.74 (dd, J ˆ 3.9 and
‡
128.43, 141.83; MS (FAB: NBA): m/z (%): 193 (10) [M ‡H]; elemental
analysis calcd for C12H16O2 ´ 1/12H2O: C 74.39, H 8.41; found: C 74.38, H
8.45. The existence of water in this product was confirmed by 1H NMR
analysis.
Cyclohexylmethyl glycidyl ether (2g): The product 2g was afforded as the
1
sole product in 87% yield from 1g as a colorless oil. H NMR (400 MHz,
Chem. Eur. J. 2000, 6, No. 12
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2203

H. Sajiki, K. Hirota, and K. Hattori
FULL PAPER
RT, CDCl3): d ˆ 0.89 ± 0.98 (m, 2H), 1.11 ± 1.29 (m, 2H), 1.55 ± 1.63 (m,
1H), 1.66 ± 1.77 (m, 6H), 2.60 (dd, J ˆ 2.9 and 4.6 Hz, 1H), 2.79 (t, J ˆ
4.6 Hz, 1H), 3.12 ± 3.16 (m, 1H), 3.25 ± 3.33 (m, 2H), 3.38 (dd, J ˆ 5.6 and
11.5 Hz, 1H), 3.69 (dd, J ˆ 3.1 and 11.5 Hz, 1H); 13C NMR (100 MHz, RT,
CDCl3): d ˆ 25.81, 26.58, 29.98, 38.05, 44.26, 50.92, 71.59, 77.46; MS (FAB:
mixture. The product ratio of 2m and 3m (95:5) was determined on the
basis of the integration ratio of the epoxide-ring protons of 2m (d ˆ 2.72,
2.87, and 3.29 ± 3.33) and the methyl proton of 3m (d ˆ 1.25, d, J ˆ 6.4 Hz).
1H NMR (400 MHz, RT, CDCl3): d ˆ 2.72 (dd, J ˆ 2.4 and 4.5 Hz, 1H), 2.87
(t, J ˆ 4.5 Hz, 1H), 3.29 ± 3.33 (m, 1H), 3.40 (brs, 2H), 3.88 (dd, J ˆ 5.9 and
11.1 Hz, 1H), 4.12 (dd, J ˆ 3.1 and 11.1 Hz, 1H), 6.62 and 6.75 (each d, J ˆ
8.8 Hz, 2H); 13C NMR (100 MHz, RT, CDCl3): d ˆ 44.67, 50.25, 69.58,
‡
NBA) m/z (%) 171 (80) [M ‡ H]; elemental analysis calcd (%) for
C10H18O2 ´ 1/4H2O: C 68.73, H 10.67; found: C 68.60, H 10.40. The existence
1
‡
of water in this product was confirmed by H NMR analysis.
115.92, 116.25, 140.53, 151.60; HRMS (FAB) calcd for C9H12O2N [M ‡H]:
166.0868, found: 166.0874.
1,2-Epoxycyclododecane (2h): The products (2h and 3h (ˆ 4h)) were
afforded from 1h as a crude mixture (2h:3h ˆ 97:3), which were identical
with the samples commercially purchased (TCI). The product 2h was
isolated by flash silica gel column chromatography (hexane/ether 5:1) in
93% yield as a colorless oil.
1-Amino-9,10-epoxydecane (2n): The product 2n was obtained in 97%
yield from 1n as a pale yellow oil. 1H NMR (400 MHz, RT, CDCl3): d ˆ
1.23 ± 1.58 (m, 14H), 2.46 (dd, J ˆ 2.7 and 4.8 Hz, 1H), 2.68 (t, J ˆ 7.1 Hz,
2H), 2.74 (t, J ˆ 4.8 Hz, 1H), 2.88 ± 2.95 (m, 1H); 13C NMR (100 MHz, RT,
CDCl3): d ˆ 25.90, 26.80, 29.32, 29.40, 29.45, 32.43, 33.64, 42.13, 47.04, 52.33;
2,3-Epoxy-3,7-dimethyl-1-octanol (2i): The product 2i was afforded as the
‡
1
HRMS (FAB) calcd. for C10H22ON [M ‡H]: 172.1701, found: 172.1705.
sole product in 86% yield from 1i as a colorless oil. H NMR (270 MHz,
RT, CDCl3): d ˆ 0.86 and 0.89 (each s, 3H), 1.16 ± 1.69 (m, 7H), 1.29 (s, 3H)
2.97 (dd, J ˆ 4.4 and 6.3 Hz, 1H), 3.69 (dd, J ˆ 6.3 and 12.3 Hz, 1H), 3.85
‡
[1] Selected review: R. C. Larock, Comprehensive Organic Transforma-
tions, VCH, New York, 1989.
(dd, J ˆ 4.4 and 12.3 Hz, 1H); HRMS (FAB) calcd for C10H21O2 [M ‡H]:
173.1541, found: 173.1555.
[2] a) F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Part B,
Plenum Press, New York, 1977; b) M. Bartok, K. L. Lang, The
Chemistry of Heterocyclic Compounds-Small Ring Heterocycles, Part 3
(Eds.: A. Weissberger, E. C. Taylor), Wiley, New York, 1985, pp. 1 ±
196 and references therein; c) P. N. Rylander, Hydrogenation Meth-
ods, Academic Press, New York, 1985, pp. 137 ± 139; d) M. Hudlicky,
Reductions in Organic Chemistry, 2nd ed., American Chemical
Society, Washington, DC, 1996, pp. 113 ± 115.
[3] a) S. W. Russell, H. J. J. Pabon, J. Chem. Soc. Perkin Trans. 1 1982,
545 ± 551; b) N. Cohen, B. L. Banner, R. J. Lopresti, F. Wong, M.
Rosenberger, Y.-Y. Liu, E. Thom, A. A. Liebman, J. Am. Chem. Soc.
1983, 105, 3661 ± 3672.
[4] D. S. Tarbell, R. M. Carman, D. D. Chapman, S. E. Cremer, A. D.
Cross, K. R. Huffman, M. Kunstmann, N. J. McCorkindale, J. G.
McNally, Jr., A. Rosowsky, F. H. L. Varina, R. L. West, J. Am. Chem.
Soc. 1961, 83, 3096 ± 3113.
[5] I. S. Cho, B. Lee, H. Alper, Tetrahedron Lett. 1995, 34, 6009 ± 6012.
[6] T. Hudlicky, G.-S. Zingde, M. G. Matchus, Tetrahedron Lett. 1987, 28,
5287 ± 5290.
[7] a) H. Sajiki, Tetrahedron Lett. 1995, 36, 3465 ± 3468; b) H. Sajiki, K. Y.
Ong, S. T. Nadler, H. E. Weges, T. J. McMurry, Synth. Commun. 1996,
26, 2511 ± 2522; c) H. Sajiki, H. Kuno, K. Hirota, Tetrahedron Lett.
1997, 38, 399 ± 402; d) H. Sajiki, H. Kuno, K. Hirota, Tetrahedron Lett.
1998, 39, 7127 ± 7130; e) H. Sajiki, K. Hirota, Tetrahedron 1998, 54,
13981 ± 13996.
[8] a) H. Sajiki, K. Hattori, K. Hirota, J. Org. Chem. 1998, 63, 7990 ±
7992; b) H. Sajiki, K. Hattori, K. Hirota, J. Chem. Soc. Perkin Trans. 1
1998, 4043 ± 4044.
[9] As shown in Table 1, 1,2-epoxydecane (2b) was hydrogenated by using
5% Pd/C(en) in MeOH to afford 2-decanol (3b) as a sole product
(19%) together with unchanged 2b (81%), whereas use of 5% Pd/C
(Aldrich) resulted in the formation of a mixture of 2-decanol (3b) and
1-decanol (4b) (82:18). These findings resulted in the development of
a new regioselective hydrogenolysis method for terminal epoxides to
secondary alcohols. See: H. Sajiki, K. Hattori, K. Hirota, Chem.
Commun. 1999, 1041 ± 1042.
1,2-Epoxypentyl 4-aminobenzoate (2j): The product 2j was afforded as the
sole product in 100% yield from 1j as a pale yellow oil. 1H NMR
(400 MHz, RT, CDCl3): d ˆ 1.66 ± 1.74 (m, 2H), 1.87 ± 1.94 (m, 2H), 2.51
(dd, J ˆ 2.9 and 4.5 Hz, 1H), 2.77 (t, J ˆ 4.5 Hz, 1H), 2.96 ± 2.99 (m, 1H),
4.05 (brs, 2H), 4.30 ± 4.33 (m, 2H), 6.64 and 7.85 (each d, J ˆ 8.6 Hz, 2H);
13C NMR (100 MHz, RT, CDCl3): d ˆ 25.36, 29.20, 47.04, 51.80, 63.76,
113.76, 119.79, 131.57, 150.85, 166.58; HRMS (FAB) calcd. for C12H16O3N
‡
[M ‡H]: 222.1130, found: 222.1120.
Glycidyl 4-aminobenzoate (2k) and 2-hydroxypropyl 4-aminobenzoate
(3k): The products (2k and 3k) were otained from 1k as a crude mixture (a
pale yellow oily solid, 99% yield as a mixture), since the isolation of 2k
from the mixture by column chromatography was difficult because of the
lability of the components of the mixture on silica gel. The quantitative
conversion of 1k was confirmed by 1H NMR spectroscopy of the crude
mixture. The product ratio of 2k and 3k (96:4) was determined on the basis
of the integration ratio of the epoxide-ring protons of 2k (d ˆ 2.72, 2.88,
and 3.31 ± 3.33) and the methyl proton of 3k (d ˆ 1.27, d, J ˆ 6.4 Hz). The
mixture was triturated with diethyl ether (5 mL) to give a small amount of
the pure 2k as a pale yellow powder. M. p. 83 ± 848C; 1H NMR (400 MHz,
RT, CDCl3): d ˆ 2.72 (dd, J ˆ 2.4 and 4.8 Hz, 1H), 2.88 (t, J ˆ 4.8 Hz, 1H),
3.31 ± 3.33 (m, 1H), 4.08 (brs, 2H), 4.12 (dd, J ˆ 6.4 and 12.3 Hz, 1H), 4.31
(dd, J ˆ 3.2 and 12.3 Hz, 1H), 6.64 and 7.88 (each d, J ˆ 8.8 Hz, 2H);
13C NMR (100 MHz, RT, CDCl3): d ˆ 44.72, 49.70, 64.78, 113.76, 119.12,
‡
131.83, 151.09, 166.25; MS (FAB: NBA): m/z 194 (%): (40) [M ‡H];
elemental analysis calcd (%) for C10H11O3N: C 62.17, H 5.74, N 7.25; found:
C 61.89, H 5.74, N, 7.20.
3-Aminobenzyl glycidyl ether (2l) and 3-aminobenzyl 2-hydroxypropyl
ether (3l): The products (2l and 3l) were obtained from 1l as a crude
mixture (a pale yellow oil, 100% yield as a mixture), since the isolation of
2l from the mixture by column chromatography was difficult because of the
lability of the components of the mixture on silica gel. The quantitative
conversion of 1l was confirmed by 1H NMR spectroscopy of the crude
mixture. The product ratio of 2l and 3l (93:7) was determined on the basis
of the integration ratio of the epoxide-ring protons of 2l (d ˆ 2.62, 2.80, and
3.16 ± 3.20) and the methyl and methine protons of 3l (d ˆ 1.13, d, J ˆ
6.4 Hz and d ˆ 3.96 ± 4.03, m, respectively). 1H NMR (400 MHz, RT,
CDCl3): d ˆ 2.62 (dd, J ˆ 2.7 and 4.8 Hz, 1H), 2.80 (t, J ˆ 4.8 Hz, 1H),
3.16 ± 3.20 (m, 1H), 3.43 (dd, J ˆ 5.9 and 11.5 Hz, 1H), 3.67 (brs, 2H), 3.75
(dd, J ˆ 2.9 and 11.5 Hz, 1H), 4.47 and 4.53 (each d, J ˆ 12.0 Hz, 1H), 6.61
(d, J ˆ 7.8 Hz, 1H), 6.70 (s, 1H), 6.72 (d, J ˆ 7.8 Hz, 1H), 7.12 (t, J ˆ 7.8 Hz,
1H); 13C NMR (100 MHz, RT, CDCl3): d ˆ 44.32, 50.89, 70.73, 73.31,
114.29, 114.51, 117.95, 129.36, 139.14, 146.59; HRMS (FAB) calcd. for
[10] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923 ± 2925.
[11] P. S. Dragovich, T. J. Prins, R. Zhou, J. Org. Chem. 1995, 60, 4922 ±
4924.
[12] a) S. Nishimura, H. Sakamoto, T. Ozawa, Chem. Lett. 1973, 855 ± 858;
b) L. Ploense, M. Salazar, B. Gurau, E. S. Smotkin, J. Am. Chem. Soc.
1997, 119, 11550 ± 11551.
[13] Direct evidence for the continuous isomerization is provided by
1H NMR spectroscopy (CDCl3) during the hydrogenation of 1a in the
presence of 5% Pd/C(en) in THF (see, Supporting Information).
[14] T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5976 ± 5978.
[15] S. Baskaran, M. H. A. Baig, S. Banerjee, C. Baskaran, K. Bhanu, S. P.
Deshpande, G. K. Trivedi, Tetrahedron 1996, 52, 6437 ± 6452.
‡
C10H14O2N [M ‡H]: 180.1025, found: 180.1018.
4-Aminophenyl glycidyl ether (2m) and 4-aminophenyl 2-hydroxypropyl
ether (3m): The products (2m and 3m) were afforded from 1m as a crude
mixture (a pale yellow oil, 94% yield as a mixture), since the isolation of
2m from the mixture by column chromatography was difficult because of
the lability of the components of the mixture on silica gel. The quantitative
conversion of 1m was confirmed by 1H NMR spectroscopy of the crude
Received: January 20, 2000 [F2247]
2204
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0947-6539/00/0612-2204 $ 17.50+.50/0
Chem. Eur. J. 2000, 6, No. 12