Chiral N-heterocyclic carbenes as asymmetric acylation catalysts

Article abstract of DOI:10.1016/j.tet.2005.09.071

Chiral N-heterocyclic carbenes are generated from C₂-symmetric 1,3-bis(1-arylethyl)imidazolium salts and potassium tert-butoxide. These C ₂-symmetric imidazolidenyl carbenes catalyze enantioselective acylation of racemic secondary alcohols. The asymmetric acylation of 1-(1-naphthyl)ethanol was achieved in up to 68% ee of the acylated product, using (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium tetrafluoroborate as a precursor of the chiral N-heterocyclic carbene and vinyl propionate as the acyl donor.

Full text of DOI:10.1016/j.tet.2005.09.071

Tetrahedron 62 (2006) 302–310
Chiral N-heterocyclic carbenes as asymmetric acylation catalysts
*
Yumiko Suzuki, Kazuyuki Muramatsu, Kaori Yamauchi, Yasuko Morie and Masayuki Sato
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
Received 1 June 2004; revised 31 August 2005; accepted 16 September 2005
Available online 10 October 2005
Abstract—Chiral N-heterocyclic carbenes are generated from C2-symmetric 1,3-bis(1-arylethyl)imidazolium salts and potassium tert-
butoxide. These C2-symmetric imidazolidenyl carbenes catalyze enantioselective acylation of racemic secondary alcohols. The asymmetric
acylation of 1-(1-naphthyl)ethanol was achieved in up to 68% ee of the acylated product, using (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium
tetrafluoroborate as a precursor of the chiral N-heterocyclic carbene and vinyl propionate as the acyl donor.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
benzoin condensation and Stetter reaction, there have been
no reports on an asymmetric catalysis using chiral NHCs in
this type of acylation reactions.10,11
The catalytic ability of azolium salts such as thiazolium and
imidazolium for benzoin/acyloin condensation was first
reported by Ukai et al. in 1943.1 Subsequently, Breslow
proposed a mechanism of azolium-catalyzed benzoin
condensation,2 which is generally accepted at present. An
N-heterocyclic carbene (NHC), derived from an azolium
salt, nucleophilically adds to an aldehyde to form an acyl
anion equivalent I. This nucleophilic intermediate adds to
an aldehyde to produce the benzoin/acyloin. Another
important example using this type of umpolung is the
Stetter reaction.3 In this case, the acyl anion equivalent
nucleophilically adds to a Michael acceptor to produce 1,4-
dicarbonyl compounds. Both reactions are synthetically
useful and have been applied to asymmetric synthesis using
chiral thiazolium and triazolium salts.4–7
As a part of our efforts focused on the development of NHC-
catalysis,12 we envisioned that the use of chiral NHC in
acylation of racemic secondary alcohols could lead to a
kinetic resolution. The kinetic resolution of racemic
alcohols catalyzed by chiral nucleophilic acylation catalysts
is one of the most intensively studied subjects of
asymmetric organocatalysis. The organic acylation catalysts
that are currently known are tertiary amines, N-hetero-
aromatic compounds, phosphines, and small-molecule
peptides.4,13 In this paper, we report asymmetric acylation
reactions catalyzed by chiral NHCs.
The other types of catalytic actions of azolium salts/NHCs
are acylation and transesterification reactions. Inoue et al.
and Castells et al. reported a thiazolium-catalyzed ester
synthesis from aldehydes and alcohols.8 In this reaction, the
acyl anion equivalent derived from thiazolidenyl carbene
and aldehyde is oxidized to 2-acylthiazolium salt II, and the
nucleophilic attack of alcohol on this intermediate at the
carbonyl group yields esters. Recently, Nolan et al. and
Hedrick et al. reported the NHC-catalyzed transesterifica-
tion reaction in which acylazolium salts such as III are
implicated as the key intermediate.9 In contrast to the
development of the asymmetric catalysis of chiral NHCs in
2. Results and discussion
N-heterocyclic carbenes derived from imidazolium and
imidazolinium salts were reported to catalyze trans-
esterification.9 However, the latter has less catalytic ability
in the transesterification than the former.9 Thus, we
examined the use of azolium salts 1–6 in an acylation of
1-(1-naphthyl)ethanol (7).
Keywords: Asymmetric acylation; Chiral N-heterocyclic carbene; Imida-
zolium; Kinetic resolution.
N-heterocyclic carbenes were generated from imidazolium
salts and used in the reactions in situ. A mixture of catalytic
amounts of imidazolium salts (3 mol%) and potassium
*
Corresponding author. Tel./fax: C81 54 264 5755;
e-mail: suzuyumi@u-shizuoka-ken.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.071

Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
303
tert-butoxide (t-BuOK, 2.5 mol%) in ether/THF was stirred
for 30 min and was followed by the addition of vinyl acetate
and 7. The results are summarized in Table 1. Benzimida-
zolium 2, triazolium 4, and imidazolium 6 proved to be
effective as a catalyst for acylation of 7, while thiazolium 1
and pyrido[1,2-c]imidazolium 3 had less catalytic ability
under these conditions. The low yield of acylated product 8
using 5 is due to the insolubility of 5 in ether.
After obtaining these results, we selected C2-symmetric
imidazolidenyl carbenes as catalysts for asymmetric
acylation. C2-symmetric imidazolium salts can be readily
prepared from inexpensive materials in one step or in two
steps (Scheme 1).14,15 We hypothesized that C2-symmetric
intermediate IV, which is formed from NHC and vinyl
acetate, has sufficient enantio selectivity to react with the
preferred enantiomer of racemic secondary alcohols
(Scheme 2). The first choice was imidazolium salts (R,R)-
9–13, which can be synthesized from commercially
available chiral amines. Imidazolium tetrafluoroborates
were prepared from the corresponding chlorides by a
reaction with silver tetrafluoroborate.
The results of the kinetic resolution of the secondary
alcohols catalyzed by (R,R)-9–13 are summarized in
Table 2. The acylation of 7 using (R,R)-914 at room
temperature provided acetate 8 in 21% yield with 42% ee
(entry 1). The unreacted 7 was recovered in 69% yield with
21% ee. At 0 8C with (R,R)-9, the selectivity was improved
(entry 2). Under the same conditions at room temperature,
the acylation of 1-phenylethanol (19) produced acetate 22 in
29% with 31% ee, and 19 was recovered in 36% yield with
20% ee (entry 13). The reaction rate increased when
tetrafluoroborate (R,R)-12 was used in the acylation of 7
(entry 5), instead of chloride (R,R)-9. The catalysts (R,R)-
10,1411, 13 had lower selectivities than (R,R)-9, (R,R)-12
(entries 3, 4, and 7). When an N-substituent of carbene is an
(R)-1-arylethyl group, the acylation of 1-arylethanols
proceeded with R-selectivities, and in the case of an (R)-
1-cyclohexylethyl group, the reaction proceeded with
S-selectivities.
Table 1. The examination of the catalytic ability of various azolium saltsa
Entry
Azolium
salt
Conditions
Yield
(%)
1
2
3
4
5
6
1
2
3
4
5
6
THF, room temperature, 16 h
Ether, room temperature, 1 h
Ether, room temperature, 2 h
Ether, room temperature, 2.5 h 35
Ether, room temperature, 1 h
THF, room temperature, 1 h
19
39
13
These results led us to assume that an aromatic substituent
on the N-ethyl group of the NHC is required to be bulkier
than the 1-naphthyl group in order to achieve a better
selectivity. Hence, imidazolium salts (R,R)-14, (R,R)-15,
(R,R)-16, (R,R)-17, and (S,S)-18 that have aromatic
substituents 9-anthryl, 1-anthryl, 1-(2-methoxynaphthyl),
17
61
a THF (1.0 M) solution was used.
Scheme 1. C2-symmetric imidazolium salts.

304
Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
slow (entries 8, 10). 9-Anthryl and 1-(2-methoxynaphthyl)
groups seem to hinder the attack of alcohol on the carbonyl
carbon of the intermediate IV (Scheme 2). (R,R)-15, (R,R)-
17, and (S,S)-18 showed enantio selectivities comparable to
(R,R)-9, (R,R)-12 (entries 9, 11, and 12).
Next, we examined the effects of various vinyl esters as acyl
donors. Vinyl propionate, vinyl butyrate, and vinyl benzoate
were employed in the reaction. The results are shown in
Table 3. In the acylation of 7 using (R,R)-12 as catalysts,
vinyl propionate functioned well as an acyl donor to
increase the enantiomeric excess of produced ester up to
68% ee with s factor 6.1.
Scheme 2. Proposed mechanism for asymmetric acylation.
Very recently, Maruoka et al. have reported kinetic
resolution of secondary alcohols by chiral NHC catalysis.16
Using 5 mol% of (R,R)-12 and bulkier vinyl esters (e.g.,
1-pyrenyl, and 9-phenanthryl, were synthesized and used in
acylation reaction of 7. Contrary to our prediction, (R,R)-14,
(R,R)-16 had lower selectivities, and the reaction rates were
Table 2. Kinetic resolution of secondary alcohols
Entry
Racemic
alcohol
Azolium salt
X
Condition
Acetate
ee
Alcohol
ee
s
Yield
(%)a
Yield
(%)a
(%)b
(%)b
1
2
7
7
7
7
7
7
7
7
7
7
(R,R)-9
(R,R)-9
Cl
Cl
Cl
Cl
BF4
BF4
BF4
BF4
BF4
BF4
Room temperature, 2 days
0 8C, 2 days
Room temperature, 18 h
Room temperature, 16 h
0 8C, 1 day
K15 8C, 3 days
0 8C, 18 h
0 8C, 2 days
Room temperature, 4 days
0 8C, 2.5 days and then
room temperature, 2 h
0 8C, 12 h
8
8
8
8
8
8
8
8
8
8
21
21
15
52
33
14
43
6
42 (R)
51 (R)
19 (S)
18 (R)
45 (R)
58 (R)
14 (R)
23 (R)
50 (R)
13 (R)
69
79
83
47
56
85
47
80
83
84
21 (S)
11 (S)
1 (R)
17 (S)
22 (S)
8 (S)
14 (S)
5 (S)
—
3.0
3.4
1.5
1.7
3.3
4.1
1.5
1.7
—
3
(R,R)-10
(R,R)-11
(R,R)-12
(R,R)-12
(R,R)-13
(R,R)-14
(R,R)-15
(R,R)-16
4c
5
6
7
8
9c
10c
17
4
!1
—
11
12
13
14
15
7
7
19
20
21
(R,R)-17
(S,S)-18
(R,R)-9
(R,R)-12
(R,R)-12
BF4
BF4
Cl
BF4
BF4
8
8
22
23
24
27
37
29
44
14
49 (R)
39 (S)
31 (R)
44 (R)
9
73
60
36
49
84
20 (S)
23 (R)
20 (S)
37 (S)
2
3.5
2.8
2.3
3.6
1.2
0 8C, 18 h
Room temperature, 3 days
0 8C, 18 h
0 8C, 2 days
a Isolated yield.
b Enantioselectivities were measured by HPLC using a Chiralcel OD column or a Chiralpac AS column.
c THF (1.0 M) solution of tBuOK was used.
Table 3. Acylation with various acyl donorsa
Entry
Acyl donor
R
Ester (ee %)b
Alcohol (ee %)b
Conversion (%)
s
1
2
3
4
Vinyl acetate
Me
Et
n-Pr
Ph
48
68
66
33
16
16
11
17
25
19
14
34
3.3
6.1
5.4
2.3
Vinyl propionate
Vinyl butyrate
Vinyl benzoate
a THF (1.0 M) solution was used.
b Enantioselectivities were measured by HPLC using a Chiralcel OD column, a Chiralcel OD-H column or a Chiralpac AD-H column.

Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
305
vinyl diphenylacetylate) at K78 to K20 8C in THF,
enantioselectivities improved up to 96% ee in asymmetric
acylation of 7, 19, 20, and related secondary alcohols.
4.3. General procedure for N-heterocyclic carbene-
catalyzed acetylation of 1-(1-naphthyl)ethanol
Potassium tert-butoxide (0.25 mmol) was added to a
suspension of azolium salt (0.3 mmol) in ether or THF
(2 mL). The mixture was stirred at room temperature for
30 min. To the mixture were added vinyl acetate (1.2 mmol)
and 7 (1 mmol). The resulting mixture was stirred at room
temperature for 1–16 h (Table 2). The solvent was
evaporated and the residue was purified by silica gel
column chromatography using ethyl acetate/n-hexane as an
eluent.
3. Conclusion
We have demonstrated that chiral N-heterocyclic carbenes
catalyze the enantioselective acylation of racemic second-
ary alcohols. We used simple C2-symmetric carbenes,
which were readily synthesized from chiral amines, glyoxal,
and formaldehyde or chloromethyl ethyl ether. Further
investigations to broaden the scope of this asymmetric
acylation are ongoing in our laboratory.
4.3.1.
1,3-Bis-[(R)-1-cyclohexylethyl]imidazolium
chloride (R,R)-10. Paraformaldehyde (120 mg, 4 mmol)
with ice cooling was added to a solution of (R)-(K)-
cyclohexylethylamine (595 mL, 4 mmol) in toluene (4 mL).
After stirring for 30 min, another equivalent of the amine
was added; subsequently, 3.3 N HCl (1.2 mL) was added
dropwise at 0 8C. 40% aqueous gyloxal solution (580 mL,
4 mmol) was added dropwise at room temperature. The
mixture was stirred for 20 h at 35 8C. Dichloromethane and
water were added to the reaction mixture. The organic layer
was taken, dried over MgSO4, and evaporated to yield crude
(R,R)-10 as a solid. Recrystallization from acetonitrile/ether
afforded (R,R)-10 as colorless prisms (364 mg, 29%); mp
188–190.5 8C; [a]D24C11.2 (c 1.0, CHCl3, 21.8 8C); 1H
NMR (CDCl3) d: 1.14 (8H, m), 1.57–1.83 (14H, m), 4.59
(2H, quintet, JZ7.4 Hz), 7.13 (2H, d, JZ1.7 Hz, imidazole
C4-H, C5-H), 11.32 (1H, s, imidazole C2-H); 13C NMR
(CDCl3) d: 18.5, 25.6, 25.7, 25.8, 29.2, 29.2, 29.3, 43.7,
62.1, 119.6, 137.9; HRMS (FAB) m/z calcd for C19H33N2
(MC): 289.2644, found: 289.2661.
4. Experimental
4.1. General
Melting points are determined using a Yazawa Micro
Melting Point Apparatus without correction. 1H NMR
(500 MHz) and 13C NMR (126 MHz) spectra were recorded
on a JEOL ECA-500 NMR spectrometer. IR spectra were
recorded on a JASCO FT/IR-8000 spectrometer and a
SHIMADZU IR Prestige-21. HRMS (FAB) spectra were
recorded on a JEOL MStation JMS-700 mass spectrometer
using m-nitrobenzyl alcohol as a matrix. Column chroma-
tography was performed with Merck Silica Gel 60 and
Silica Gel 60 N (spherical, neutral, Kanto Chemical Co.,
Inc.). Optical rotations were measured using a JASCO
DIP-360 or a JASCO P-1030 polarimeter.
4.2. Preparation of imidazolium chlorides: general
procedure
4.3.2. 1,3-Bis-[(R)-1-(1-naphthyl)ethyl]imidazolium
tetrafluoroborate (R,R)-12. AgBF4 (90%) in hexane
(476 mg, 2.2 mmol) was added to a solution of 1,3-bis-
[(R)-1-(1-naphthyl)ethyl]imidazolium chloride (413 mg,
1 mmol) in dichloromethane (5 mL). The mixture was
stirred for 2 h at room temperature. The resulting
precipitates were filtered. The filtrate was purified by silica
gel column chromatography using dichloromethane/
methanol as an eluent to yield (R,R)-12 (279 mg, 60%) as
4.2.1. Glyoxal-bis-[1-(1-adamantyl)ethyl]imine.
A
mixture of 40% aqueous solution of glyoxal (145 mg,
1 mmol), 1-propanol (0.16 mL), and water (0.4 mL) was
added to a solution of racemic 1-(1-adamantyl)ethylamine
(360 mg, 2 mmol) in 1-propanol (1.4 mL) at room tempera-
ture. The mixture was stirred at 70 8C for 2 h. Water was
added to the mixture, and the resulting colorless precipitates
were filtered, washed with water, and dried. The precipitates
were identified as imine (335 mg, 88%) by 1H NMR
spectroscopy, and used in the subsequent reaction without
further purification.
1
a coloreless solid; [a]D24K88.7 (c 1.0, CHCl3, 21.7 8C); H
NMR (CDCl3) d: 2.13 (6H, d, JZ6.5 Hz, CH3CH), 6.85
(2H, q, JZ6.5 Hz, CH3CH), 6.90 (2H, s), 7.41–7.54 (8H,
m), 7.83–7.84 (4H, m), 8.15 (2H, d, JZ8.5 Hz), 11.59 (1H,
s, imidazole C2-H); 13C NMR (CDCl3) d: 21.6, 56.2, 120.6,
122.4, 124.5, 125.3, 126.5, 127.8, 129.2, 130.4, 130.5,
133.0, 134.0, 137.3.
4.2.2.
chloride 6.
1,3-Bis-[1-(1-adamantyl)ethyl]imidazolium
solution of glyoxal-bis-[1-(1-
A
adamantyl)ethyl]imine (337 mg, 0.89 mmol) and one drop
of water in THF (1.9 mL) was added to a solution of
chloromethyl ethyl ether (96%, 88 mg, 0.89 mmol) and
THF (0.2 mL) in a 10 mL single-necked flask. The flask was
sealed under nitrogen with a septum and the mixture was
stirred at room temperature for 24 h, and then at 40 8C for
15 h. Water and dichloromethane were added to the reaction
mixture. The organic layer was taken, dried over MgSO4,
and evaporated. The residue was purified by silica gel
column chromatography using dichloromethane/methanol
as an eluent to afford 6 as a solid (145 mg, 39%). This
product is assumed to comprise a mixture of meso and
racemic forms.
4.4. Preparation of 1,3-bis-[(R)-1-(2-naphthyl)ethyl]-
imidazolium tetrafluoroborate (R,R)-13
4.4.1.
Glyoxal-bis-[(R)-1-(2-naphthyl)ethyl]imine.
Following the general procedure given for the glyoxal-bis-
imine, (R)-(C)-1-(2-naphthyl)ethylamine (342 mg,
2 mmol) was reacted with glyoxal for 4 h at 60 8C. The
crude imine (362 mg, 99%) was extracted with ether. The
product was used in the subsequent reaction without further
1
purification; H NMR (CDCl3) d: 1.72 (6H, d, JZ6.9 Hz,
CH3CH), 4.73 (2H, q, JZ6.9 Hz, CH3CH), 7.45–7.50 (4H,

306
Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
m), 7.53 (2H, dd, JZ8.6, 1.7 Hz), 7.82–7.86 (8H, m), 8.2
(2H, s).
4.6. Preparation of 1,3-bis-[(R)-1-(1-anthryl)ethyl]-
imidazolium tetrafluoroborate (R,R)-9
4.6.1. (R)-(C)-1-(1-anthryl)ethylamine. A solution of
1-(1-anthranyl)ethylamine18 (312 mg, 1.41 mmol) and (R)-
16-hydroxy-14-oxabicyclo[11.2.2]heptadecane-1(16),
13(17)-diene-2,15-dione19,20 (392 mg, 1.41 mmol) in ben-
zene (14 mL) was refluxed for 2 h. After evaporation of the
solvent, the residue was purified by column chromatography
on neutral silica gel by using hexane/ethyl acetate 4:1 as an
eluent to first yield (R,R)-2-[1-(1-anthranyl)ethylamino]-14-
oxabicyclo[11.2.2]heptadecane-1(2),13(17)-diene-15,16-
dione (428 mg, 33%), and then (R,S)-2-[1-(1-anthranyl)-
ethylamino]-14-oxabicyclo[11.2.2]heptadecane-1(2),
13(17)-diene-15,16-dione (147 mg, 20%).
4.4.2. 1,3-Bis-[(R)-1-(2-naphthyl)ethyl]imidazolium
chloride. Following the general procedure given for 6,
glyoxal-bis-[(R)-1-(2-naphthyl)ethyl]imine
(362 mg,
0.995 mmol) was reacted with chloromethyl ethyl ether at
40 8C for 18 h to afford imidazolium chloride (122 mg,
30%) as a yellow amorphous solid; [a]2D4C49.9 (c 1.0,
1
CHCl3, 22.8 8C); H NMR (CDCl3) d: 2.03 (6H, d, JZ
6.9 Hz, CH3CH), 6.16 (2H, q, JZ6.9 Hz, CH3CH), 7.22
(2H, d, JZ1.2 Hz), 7.40–7.45 (4H, m), 7.48 (2H, dd, JZ
8.5, 1.9 Hz), 7.71–7.78 (6H, m), 7.90 (2H, s), 11.32 (1H, s,
imidazole C2-H); 13C NMR (CDCl3) d: 21.2, 60.0, 120.7,
124.2, 126.6, 126.9, 127.1, 127.8, 128.3, 129.6, 133.1,
133.4, 135.3, 136.6; C27H25N2 (MC): 377.2018, found:
477.2056.
(R,R)-2-[1-(1-anthranyl)ethylamino]-14-oxabicyclo[11.2.2]
heptadecane-1(2),13(17)-diene-15,16-dione. Colorless
needles (dichloromethane/ether); mp 199–202 8C; [a]2D4K
327.9 (c 1.0, CHCl3, 21.6 8C); 1H NMR (CDCl3) d:
1.11–1.34 (10H, m), 1.44–1.52 (2H, m), 1.61–1.72 (3H,
m), 1.78–1.90 (4H, m), 2.18–2.24 (2H, m), 2.60 (1H, dt, JZ
14.3, 4.5 Hz), 4.05 (1H, br), 5.82–5.86 (2H, m), 7.42–7.45
(2H, m), 7.50–7.54 (2H, m), 7.96–7.98 (1H, m), 8.02–8.08
(2H, m), 8.49 (1H, s), 8.51 (1H, s), 14.37 (1H, br, NH);
HRMS (FAB) m/z calcd for C32H36NO3 (MC1): 437.2229,
found: 437.2230.
4.4.3. 1,3-Bis-[(R)-1-(2-naphthyl)ethyl]imidazolium
tetrafluoroborate (R,R)-13. Following the procedure
given for (R,R)-12, 1,3-bis-[(R)-1-(2-naphthyl)ethyl]imida-
zolium chloride was treated with AgBF4 to yield (R,R)-13
(70%) as a yellow amorphous solid. This compound was
used in the acylation reaction without further purification.
4.5. Preparation of 1,3-bis-[(R)-1-(9-anthryl)ethyl]-
imidazolium tetrafluoroborate (R,R)-14
(R,S)-2-[1-(1-anthranyl)ethylamino]-14-oxabicyclo[11.2.2]
heptadecane-1(2),13(17)-diene-15,16-dione. Colorless
prisms (ether); mp 146–149 8C; [a]2D4C677.6 (c 1.0,
4.5.1.
Glyoxal-bis-[(R)-1-(9-anthryl)ethyl]imine.
Following the general procedure given for glyoxal-bis-
imine, (R)-(C)-1-(9-anthryl)ethylamine17 (221 mg,
1 mmol), was reacted with glyoxal for 2 h at 60 8C. The
crude imine (202 mg, 87%) was extracted with dichloro-
methane. The product was used in the subsequent reaction
without further purification; 1H NMR (CDCl3) d: 1.97 (6H,
d, JZ7.4 Hz, CH3CH), 6.08 (2H, d, JZ7.4 Hz, CH3CH),
7.38–7.40 (8H, m), 7.94–7.96 (4H, m), 8.08 (2H, s), 8.34
(2H, s), 8.42 (4H, br).
1
CHCl3, 22.1 8C); H NMR (CDCl3) d: 0.62–1.03 (7H, m),
1.08–1.23 (5H, m), 1.26–1.34 (1H, m), 1.42–1.49 (1H, m),
1.58–1.67 (1H, m), 1.72–1.82 (1H, m), 1.85 (3H, d, JZ
6.5 Hz), 2.16–2.22 (1H, m), 2.59 (1H, dt, JZ13.6, 4.5 Hz),
2.72 (1H, br), 4.35 (1H, br), 5.83 (1H, s), 5.95–6.01 (1H, m),
7.44 (1H, dd, JZ7.8, 7.1 Hz), 7.49–7.56 (3H, m), 7.94 (1H,
d, JZ8.4 Hz), 8.00 (1H, d, JZ7.8 Hz), 8.08 (1H, d, JZ
7.8 Hz), 8.47 (1H, s), 8.52 (1H, s), 14.50 (1H, br, NH); 13C
NMR (CDCl3) d: 23.9, 26.1, 26.6, 26.8, 28.5, 28.6, 33.9,
51.4, 98.7, 108.8, 120.6, 122.4, 125.0, 126.1, 126.2, 128.0,
128.1, 128.5, 128.9, 131.6, 132.0, 137.6, 164.6, 166.1,
178.0, 183.7; HRMS (FAB) m/z calcd for C32H36NO3 (MC
1): 437.2229, found: 437.2230.
4.5.2.
chloride. Following the general procedure given for 6,
glyoxal-bis-[(R)-1-(9-anthryl)ethyl]imine (223 mg,
1,3-Bis-[(R)-1-(9-anthryl)ethyl]imidazolium
0.48 mmol) was reacted with chloromethyl ethyl ether at
40 8C for 64 h. The addition of water to the reaction mixture
afforded precipitates of imidazolium chloride (224 mg,
91%). Slight brown granules (dichloromethane/ether); mp
161–162.5 8C; [a]D24K88.7 (c 1.0, CHCl3, 21.7 8C); 1H
NMR (CDCl3) d: 2.51 (6H, d, JZ6.9 Hz, CH3CH), 6.75
(2H, d, JZ1.7 Hz), 7.29 (2H, q, JZ6.9 Hz, CH3CH), 7.46–
7.52 (8H, m), 8.03–8.11 (8H, m), 8.53 (2H, s), 10.10 (1H, s);
13C NMR (CDCl3) d: 21.3, 56.4, 120.8, 122.5, 123.1, 123.6,
126.2, 127.2, 127.3, 127.8, 128.1, 128.9, 129.3, 130.5,
130.7, 130.9, 131.2, 136.6; HRMS (FAB) m/z calcd for
C35H29N2 (MC): 477.2331, found: 477.2310.
A
solution
of
(R,R)-2-[1-(anthranyl)amino]-14-
oxabicyclo[11.2.2]heptadecane-1(2),13(17)-diene-15,16-
dione (384 mg, 0.8 mmol) and KOH (179 mg, 3.2 mmol) in
THF (10 mL)/H2O (10 mL) was stirred for 20 h at room
temperature. The mixture was alkalized with 10% aqueous
KOH solution and extracted with dichloromethane. The
organic layer was washed with brine, dried over K2CO3, and
concentrated to give (R)-amine (176 mg, 99%). Colorless
needles (ether); mp 62–64 8C; [a]2D4C4.8 (c 0.6, CHCl3,
21.2 8C).
4.6.2.
Following the general procedure given for glyoxal-bis-
imine, (R)-(C)-1-(1-anthryl)ethylamine (177 mg,
0.8 mmol) was reacted with glyoxal for 2 h at 70 8C. The
crude imine (202 mg, 87%) was extracted with ethyl
acetate. This product was used in the subsequent reaction
without further purification; 1H NMR (CDCl3) d: 1.79 (6H,
Glyoxal-bis-[(R)-1-(1-anthryl)ethyl]imine.
4.5.3. 1,3-Bis-[(R)-1-(9-anthryl)ethyl]imidazolium tetra-
fluoroborate (R,R)-14. Following the procedure given for
(R,R)-12, 1,3-bis-[(R)-1-(9-anthryl)ethyl]imidazolium
chloride was treated with AgBF4 to yield (R,R)-14 (61%)
as a slight brown solid. This compound was used in the
acylation reaction without further purification.

Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
307
d, JZ6.3 Hz, CH3CH), 5.56 (2H, q, JZ6.3 Hz, CH3CH),
7.41–7.48 (6H, m), 7.62 (2H, d, JZ6.9 Hz), 7.91 (2H, d, JZ
8.6 Hz), 7.97–8.03 (4H, m), 8.22 (2H, s), 8.43 (2H, s), 8.65
(2H, s).
solution, and extracted with ether. The organic layer was
washed with brine, dried over K2CO3, and evaporated to
yield the amine (424 mg, 70%). Colorless prisms (ether);
mp 49–51 8C; 1H NMR (CDCl3) d: 1.59 (3H, d, JZ6.9 Hz,
CH3CH), 2.11 (2H, br, NH2), 3.95 (3H, s, CH3O), 4.97 (1H,
q, JZ6.9 Hz, CH3CH), 7.26 (1H, d, JZ9.2 Hz), 7.33 (1H, t,
JZ7.4 Hz), 7.47 (1H, dd, JZ8.6, 7.4 Hz), 7.73 (1H, d, JZ
9.2 Hz), 7.78 (1H, d, JZ8.0 Hz), 8.16 (1H, d, JZ8.6 Hz);
13C NMR (CDCl3) d: 23.2, 45.5, 56.2, 114.0, 122.9, 123.4,
126.5, 128.0, 128.5, 128.8, 129.5, 131.7, 155.1; HRMS
(FAB) m/z calcd for C13H16NO (MC1): 202.1232, found:
202.1228.
4.6.3.
1,3-Bis-[(R)-1-(1-anthryl)ethyl]imidazolium
chloride. Following the general procedure given for 1,3-
bis-[1-(1-adamantyl)ethyl]imidazolium chloride, glyoxal-
bis-[(R)-1-(1-anthryl)ethyl]imine (171 mg, 0.37 mmol)
was reacted with chloromethyl ethyl ether at 40 8C for
15 h. After addition of THF (2 mL), the mixture was
refluxed for 8 h to afford imidazolium chloride (112 mg,
60%) as a yellow solid; mp 162–166 8C (dichloromethane/
1
ether); [a]2D4K298.6 (c 0.26, CHCl3, 21.7 8C); H NMR
4.7.2. (R)-(+)-1-[1-(2-methoxynaphthyl)]ethylamine.
Following the procedure given for (R)-(C)-1-(1-anthryl)
ethylamine, racemic 1-(2-methoxynaphthyl)ethylamine was
resoluted. The (R,R)- and (R,S)-diastereomers were purified
by column chromatography on neutral silica gel by using
dichloromethane/hexane/ether 10:5:1 as an eluent.
(DMSO-d6) 2.09 (6H, d, JZ6.9 Hz, CH3CH), 6.73 (2H, q,
JZ6.9 Hz, CH3CH), 7.37 (2H, d, JZ8.0 Hz), 7.41–7.45
(4H, m), 7.51 (2H, t, JZ7.5 Hz), 7.83–7.84 (2H, m), 8.05
(2H, d, JZ8.6 Hz), 8.09 (2H, d, JZ8.0 Hz), 8.61 (2H, s),
8.65 (2H, s), 9.89 (1H, s); 13C NMR (CDCl3) d: 21.4, 56.3,
120.0, 121.5, 124.0, 124.0, 126.2, 126.3, 127.4, 127.5,
128.2, 129.0, 130.6, 131.5, 131.6, 132.4, 132.7, 137.8;
HRMS (FAB) m/z calcd for C35H29N2 (MC): 477.2331,
found: 477.2310.
(R,R)-2-{1-[1-(2-methoxynaphthyl)]ethylamino}-14-oxabi-
cyclo[11.2.2]heptadecane-1(2),13(17)-diene-15,16-dione.
Yield 32%; colorless needles (dichloromethane/ether); mp
149–150 8C; [a]2D4K271.4 (c 1.0, CHCl3, 21.7 8C); 1H NMR
(CDCl3) d: 0.97–1.42 (12H, m), 1.48–1.55 (3H, m), 1.62–
1.86 (4H, m), 2.05 (1H, t, JZ12.0 Hz), 2.30–2.46 (2H, m),
3.93 (3H, d, JZ2.9 Hz), 4.00 (1H, br), 5.65 (1H, s), 5.79
(1H, br), 7.20 (1H, dd, JZ9.2, 2.9 Hz), 7.28 (1H, t, JZ
6.9 Hz), 7.45 (1H, t, JZ6.9 Hz), 7.72–7.75 (2H, m), 7.84
(1H, d, JZ8.0 Hz), 14.1 (1H, br, NH); 13C NMR (CDCl3) d:
20.6, 24.0, 25.48, 26.5, 27.1, 27.2, 27.5, 28.2, 28.6, 28.8,
33.9, 47.9, 56.4, 98.0, 109.0, 113.6, 121.3, 123.7, 127.8,
129.4, 130.5, 131.0, 164.9, 165.1, 165.4, 183.3; HRMS
(FAB) m/z calcd for C29H36NO4 (MC1): 462.2644, found:
462.2655.
4.6.4. 1,3-Bis-[(R)-1-(1-anthryl)ethyl]imidazolium tetra-
fluoroborate (R,R)-15. Following the procedure given for
1,3-bis-[(R)-1-(1-naphthyl)ethyl]imidazolium tetrafluoro-
borate (R,R)-12, 1,3-bis-[(R)-1-(1-anthryl)ethyl]imidazo-
lium chloride was treated with AgBF4 to give (R,R)-15
(80%) as a slight brown solid. This compound was used in
the acylation reaction without further purification.
4.7. Preparation of 1,3-bis-{(R)-1-[1-(2-methoxy-
naphthyl)]ethyl}imidazolium tetrafluoroborate (R,R)-10
4.7.1. 1-[1-(2-Methoxynaphthyl)]ethylamine. Diethyl
azodicarboxylate (40% in toluene, 2 mL) at room tempera-
ture was added to a solution of 1-[1-(2-methoxynaphthyl)]
ethanol21 (727 mg, 3.6 mmol), phthalimide (573 mg,
4 mmol), and triphenylphosphine (1.05 g, 4 mmol) in dry
THF (20 mL). The mixture was stirred overnight at room
temperature. The solvent was evaporated and the residue
was purified by silica gel column chromatography using
hexane/ethyl acetate 2:1 as an eluent to yield N-1-[1-(2-
methoxynaphthyl)]ethylphthalimide (989 mg, 83%). Color-
less needles (ethyl acetate/hexane); mp 144–145 8C; 1H
NMR (CDCl3) d: 2.12 (3H, d, JZ7.4 Hz, CH3CH), 3.95
(3H, s, CH3O), 6.31 (1H, q, JZ7.4 Hz, CH3CH), 7.27 (1H,
d, JZ8.6 Hz), 7.31–7.34 (1H, m), 7.51 (1H, t, JZ7.4 Hz),
7.63–7.64 (2H, m), 7.75–7.79 (4H, m), 8.25 (1H, d, JZ
9.2 Hz); 13C NMR (CDCl3) d: 18.5, 46.9, 56.8, 114.4, 121.5,
122.6, 123.0, 123.5, 27.1, 129.0, 129.4, 130.0, 132.1, 132.2,
133.8, 155.9, 168.9; HRMS (FAB) m/z calcd for C21H17NO3
(MC): 331.1208, found: 331.1203.
(R,S)-2-{1-[1-(2-methoxynaphthyl)]ethylamino}-14-oxabi-
cyclo[11.2.2]heptadecane-1(2),13(17)-diene-15,16-dione.
Yield 24%; colorless powder (ether); mp 127–128 8C;
[a]2D4C206.9 (c 1.0, CHCl3, 21.2 8C); 1H NMR (CDCl3) d:
0.74–1.17 (12H, m), 1.34–1.44 (1H, br), 1.50–1.63 (2H, m),
1.68–1.80 (4H, m), 2.08–2.14 (1H, m), 2.55 (1H, dt, JZ
13.6, 4.5 Hz), 2.72 (1H, br), 4.08 (3H, s, CH3O), 4.20 (1H,
br), 5.69 (1H, s), 5.92–5.94 (1H, m), 7.31 (1H, d, JZ
9.1 Hz), 7.36 (1H, t, JZ7.1 Hz), 7.53–7.57 (1H, m), 7.81–
7.84 (2H, m), 7.97 (1H, d, JZ9.1 Hz), 14.2 (1H, br, NH);
HRMS (FAB) m/z calcd for C29H36NO4 (MC1): 462.2644,
found: 462.2655.
(R)-(C)-1-[1-(2-methoxynaphthyl)]ethylamine. [a]2D4C
30.7 (c 1.0, CHCl3, 24.4 8C).
4.7.3. Glyoxal-bis-{(R)-1-[1-(2-methoxynaphthyl)]ethyl}-
imine. Following the general procedure given for glyoxal-
bis-imine, (R)-(C)-1-[1-(2-methoxynaphthyl)]ethylamine
was reacted with glyoxal for 2 h at 60 8C. The crude
imine (brown oil, 98%) was extracted with dichloro-
methane. This product was used in the subsequent reaction
without further purification; 1H NMR (CDCl3) d: 1.80 (6H,
d, JZ6.9 Hz, CH3CH), 3.86 (6H, s, CH3O), 5.73 (2H, q, JZ
6.9 Hz, CH3CH), 7.21 (2H, dd, JZ9.2, 1.7 Hz), 7.29 (2H, t,
JZ6.9 Hz), 7.37 (2H, dd, JZ8.6, 6.9 Hz), 7.72–7.75 (4H,
m), 8.03 (2H, s), 8.21 (2H, d, JZ8.6 Hz).
A solution of N-1-[1-(2-methoxynaphthyl)]ethylphthal-
imide (993 mg, 3 mmol) and hydrazine monohydrate
(0.3 mL) in THF (30 mL) was refluxed for 3.5 h. Ether
was added to the reaction mixture and the resulting
precipitates were filtered. The filtrate was alkalized with
KOH aqueous solution to pH 11. The organic layer was
taken and extracted with 10% aqueous solution. The
aqueous layer was taken, alkalized with NaOH aqueous

308
Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
4.7.4. 1,3-Bis-{(R)-1-[1-(2-methoxynaphthyl)]ethyl}-
imidazolium chloride. Following the general procedure
given for 6, glyoxal-bis-{(R)-1-[1-(2-methoxynaphthyl)]-
ethyl}imine (212 mg, 0.5 mmol) was reacted with chloro-
methy ethyl ether at 40 8C for 20 h. After addition of THF
(2 mL), the mixture was refluxed for 24 h to afford
imidazolium chloride (104 mg, 44%) as a brown amorphous
solid; [a]2D4K96.6 (c 0.54, CHCl3, 20.8 8C); 1H NMR
(CDCl3) d: 2.19 (6H, d, JZ6.3 Hz, CH3CH), 3.69 (6H, s,
CH3O), 6.74 (2H, q, JZ6.3 Hz, CH3CH), 7.09 (2H, s), 7.18
(2H, d, JZ9.2 Hz), 7.31 (2H, dd, JZ8.0, 6.9 Hz), 7.50 (2H,
t, JZ6.9 Hz), 7.75 (2H, d, JZ8.0 Hz), 7.82 (2H, d, JZ
8.6 Hz), 8.16 (2H, br), 10.47 (1H, s, imidazole C2-H); 13C
NMR (CDCl3) d: 19.4, 53.6, 56.2, 113.3, 118.2, 120.9,
122.0, 124.2, 128.3, 129.1, 129.3, 131.69, 131.8, 136.7,
155.8; HRMS (FAB) m/z calcd for C29H29N2O2 (MC):
437.2229, found: 437.2230.
(R,R)-12, 1,3-bis-[(R)-1-(1-pyrenyl)ethyl]imidazolium
chloride was treated with AgBF4 to give (R,R)-17 (60%)
as a slight brown solid. This compound was used in the
acylation reaction without further purification.
4.9. Preparation of 1,3-bis-[(S)-1-(9-phenanthryl)ethyl]
imidazolium tetrafluoroborate (S,S)-18
4.9.1. Glyoxal-bis-[(S)-1-(9-phenanthryl)ethyl]imine.
Following the general procedure given for glyoxal-bis-
imine, (S)-(K)-1-(9-phenanthryl)ethylamine23 (69 mg,
0.8 mmol) was reacted with glyoxal for 30 min at room
temperature, and then for 2 h at 60 8C. The imine was
quantitively obtained by extraction with dichloromethane
and used in the subsequent reaction without further
1
purification; H NMR (CDCl3) d: 1.80 (6H, d, JZ6.9 Hz,
CH3CH), 5.45 (2H, q, JZ6.9 Hz, CH3CH), 7.56–7.69 (8H,
m), 7.88 (2H, d, JZ8.0 Hz), 7.95 (2H, s), 8.17 (2H, d, JZ
9.2 Hz), 8.27 (2H,s), 8.64 (2H, d, JZ8.0 Hz), 8.74 (2H, d,
JZ9.2 Hz).
4.7.5. 1,3-Bis-{(R)-1-[1-(2-methoxynaphthyl)]ethyl}-
imidazolium tetrafluoroborate (R,R)-16. Following the
procedure given for (R,R)-12, 1,3-bis-{(R)-1-[1-(2-
methoxynaphthyl)]ethyl}imidazolium chloride was treated
with AgBF4 to give (R,R)-16 (77%) as a solid. This
compound was used in the acylation reaction without further
purification.
4.9.2. 1,3-Bis-[(S)-1-(9-phenanthryl)ethyl]imidazolium
chloride. Following the general procedure given for 6,
glyoxal-bis-[(S)-1-(9-phenanthryl)ethyl]imine (186 mg,
0.4 mmol) was reacted with chloromethyl ethyl ether at
40 8C for 20 h to afford the imidazolium chloride (104 mg,
60%) as a solid. Slight yellow powder (dichloromethane/
ether); mp 177–180 8C; [a]2D4K69.6 (c 1.0, CHCl3, 23.0 8C);
1H NMR (CDCl3) d: 2.09 (6H, d, JZ6.8 Hz, CH3CH), 6.72
(2H, q, JZ6.8 Hz, CH3CH), 6.87 (2H, s), 7.51–7.61 (8H,
m), 7.63 (2H, s), 7.75 (2H, d, JZ8.0 Hz), 8.01 (2H, d, JZ
7.9 Hz), 8.50 (2H, d, JZ8.6 Hz), 8.58 (2H, d, JZ8.0 Hz),
10.83 (1H, s); 13C NMR (CDCl3) d: 21.5, 56.3, 120.7, 122.5,
123.3, 123.6, 126.1, 127.2, 127.2, 127.8, 128.0, 128.9,
129.3, 130.5, 130.7, 130.9, 131.4, 137.3.
4.8. Preparation of 1,3-bis-(R)-1-1-pyrenylimidazolium
tetrafluoroborate (R,R)-11
4.8.1. Glyoxal-bis-[(R)-1-(1-pyrenyl)ethyl]imine. Follow-
ing the general procedure given for glyoxal-bis-imine, (R)-
(C)-1-(1-pyrenyl)ethylamine22 (245 mg, 2 mmol) was
reacted with glyoxal at 60 8C for 3 h. The extraction with
dichloromethane yielded the crude imine quantitively as a
slight brown solid. The product was used in the subsequent
1
reaction without further purification; H NMR (CDCl3) d:
1.85 (6H, d, JZ6.9 Hz, CH3CH), 5.71 (2H, q, JZ6.9 Hz,
CH3CH), 7.97 (2H, t, JZ7.4 Hz), 8.00 (4H, s), 8.08 (2H, d,
JZ9.2 Hz), 8.13–8.15 (6H, m), 8.21 (2H, d, JZ8.0 Hz),
8.27 (2H, s), 8.33 (2H, d, JZ9.2 Hz).
4.9.3. 1,3-Bis-[(S)-1-(9-phenanthryl)ethyl]imidazolium
tetrafluoroborate (S,S)-18. Following the procedure
given for (R,R)-12, 1,3-bis-[(S)-1-(9-phenanthryl)ethyl]-
imidazolium chloride was treated with AgBF4 to give
(R,R)-18 (61%) as a slight brown solid. This compound was
used in the acylation reaction without further purification.
4.8.2.
chloride. Following the general procedure given for 6,
glyoxal-bis-[(R)-1-(1-pyrenyl)ethyl]imine (492 mg,
1,3-Bis-[(R)-1-(1-pyrenyl)ethyl]imidazolium
4.10. General procedure for N-heterocyclic carbene-
catalyzed asymmetric aclation of secondary alcohols
0.96 mmol) was reacted with chloromethyl ethyl ether at
room temperature for 1 h, and then for 16 h at 40 8C. The
resulting precipitates were collected by filtration and
dissolved in dichloromethane/methanol. The solution was
treated by an activated carbon and evaporated to afford the
chloride (351 mg, 65%). Slight yellow granules (methanol/
ether); mp 240–245 8C (decomp); [a]2D4K32.5 (c 0.16,
EtOH, 23.3 8C); 1H NMR (CDCl3) d: 2.29 (6H, d, JZ
6.7 Hz, CH3CH), 7.10 (2H, q, JZ6.7 Hz, CH3CH), 6.65
(2H, s), 7.93 (2H, d, JZ8.0 Hz), 7.96 (2H, d, JZ9.2 Hz),
8.00 (2H, t, JZ7.4 Hz), 8.05 (2H, d, JZ8.6 Hz), 8.07 (2H,
d, JZ8.0 Hz), 8.13–8.19 (6H, m), 8.41 (2H, d, JZ9.2 Hz),
11.76 (1H, s); 13C NMR (CDCl3) d: 20.2, 47.5, 121.0, 122.1,
124.3, 124.7, 125.1, 125.4, 125.7, 126.3, 126.9, 127.9,
128.0, 128.6, 130.6, 131.3, 131.4, 131.6; HRMS (FAB) m/z
calcd for C39H29N2 (MC): 525.2331, found: 525.2340.
Potassium tert-butoxide (0.25 mmol) was added to a
suspension of azolium salt (0.3 mmol) in ether (2 mL).
The mixture was stirred at room temperature for 30 min.
Vinyl acetate (1.2 mmol) and alcohol (1 mmol) were added
at the indicated temperature to the mixture. The resulting
mixture was stirred for the indicated time. The solvent was
evaporated and the residue was purified by silica gel column
chromatography by using ethyl acetate/hexane.
The results summarized in Table 3 were obtained by taking
5 mL of the sample from the reaction mixture, filtering it
through a short silica gel column, and then subjecting to
chiral HPLC analysis.
4.10.1. 1-(1-Naphthyl)ethanol 7. Analytical chiral HPLC:
Chiralcel OD column, 0.46!25 cm, hexane/2-propanol 9:1,
0.5 mL minK1; S, 19.8 min, R, 29.4 min. Chiralcel OD-H
4.8.3. 1,3-Bis-[(R)-1-(1-pyrenyl)ethyl]imidazolium tetra-
fluoroborate (R,R)-17. Following the procedure given for

Y. Suzuki et al. / Tetrahedron 62 (2006) 302–310
309
column, 0.46!15 cm, hexane/2-propanol 9:1, 1 mL minK1
S, 6.2 min, R, 9.7 min.
;
1974, 39, 1196–1199. (c) Takagi, W.; Tamura, Y.; Yano, Y.
Bull. Chem. Soc. Jpn. 1980, 53, 478–480. (d) Zhao, C.; Chen,
S.; Wu, P.; Wen, Z. Huaxue Xuebao 1988, 46, 784–790. (e)
Marti, J.; Castells, J.; Lopez-Calahorra, F. Tetrahedron Lett.
1993, 34, 521–524. (f) Enders, D.; Breuer, K. Helv. Chim. Acta
1996, 79, 1217–1221. (g) Knight, R. L.; Leeper, F. J.
Tetrahedron Lett. 1997, 38, 3611–3614. (h) Gerhards, A. U.;
Leeper, F. J. Tetrahedron Lett. 1997, 38, 3615–3618. (i)
Dvorak, C. A.; Rawal, V. H. Tetrahedron Lett. 1998, 39,
2925–2928. (j) Knight, R. L.; Leeper, F. J. J. Chem. Soc.,
Perkin Trans. 1 1998, 1891–1893. (k) Enders, D.; Kallfass, U.
Angew. Chem., Int. Ed. 2002, 41, 1743–1745.
4.10.2. 1-(1-Naphthyl)ethyl acetate 8. Analytical chiral
HPLC: Chiralcel OD column, 0.46!25 cm, hexane/
2-propanol 9:1, 1 mL minK1; R, 5.3 min, S, 6.4 min.
4.10.3. 1-(1-Phenyl)ethanol 19. Analytical chiral HPLC:
Chiralcel OD column, 0.46!25 cm, hexane/2-propanol
95:5, 0.5 mL minK1; S, 16.5 min, R, 19.7 min.
4.10.4. 1-(1-Phenyl)ethyl acetate 22. Analytical chiral
HPLC: Chiralpac AS column, 0.46!25 cm, hexane/
2-propanol 100:0.1, 0.5 mL minK1; R, 15.8 min, S,
19.8 min.
7. (a) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. Helv. Chim.
Acta 1996, 79, 1899–1902. (b) Kerr, M. S.; Read de Alaniz, J.;
Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298–10299. (c) Kerr,
M. S.; Rovis, T. Synlett 2003, 1934–1936.
8. (a) Inoue, H.; Higashiura, K. J. Chem. Soc., Chem. Commun.
´
1980, 549–550. (b) Castells, J.; Pujol, F.; Llitjos, H.;
4.10.5. 1-(2-Naphthyl)ethanol 20. Analytical chiral HPLC:
Chiralpac AS column, 0.46!25 cm, hexane/2-propanol
97.5:2.5, 0.5 mL minK1; S, 30.1 min, R, 35.1 min.
Moreno-Man˜as, M. Tetrahedron 1982, 38, 337–346.
9. (a) Grasa, G. A.; Kissling, R. M.; Nolan, S. P. Org. Lett. 2002,
4, 3583–3586. (b) Nyce, G. W.; Lamboy, J. A.; Connor, E. F.;
Waymouth, R. M.; Hedrick, J. L. Org. Lett. 2002, 4,
3587–3590. (c) Grasa, G. A.; Gu¨veli, T.; Singh, R.; Nolan,
S. P. J. Org. Chem. 2003, 68, 2812–2819. (d) Singh, R.;
Kissling, R. M.; Letellier, M.-A.; Nolan, S. P. J. Org. Chem.
2004, 69, 209–212.
4.10.6. 1-(2-Naphthyl)ethyl acetate 23. Analytical chiral
HPLC: Chiralpac AS column, 0.46!25 cm, hexane/
2-propanol 99:1, 0.5 mL minK1; R, 13.5 min, S, 16.3 min.
4.10.7. 1,2,3,4-Tetrahydro-1-naphtol 21. Analytical chiral
HPLC: Chiralpac AS column, 0.46!25 cm, hexane/
2-propanol 97.5:2.5, 0.5 mL minK1; 20.6 min, 26.6 min.
10. A preliminary communication of this work was published:
Suzuki, Y.; Yamauchi, K.; Muramatsu, K.; Sato, M. Chem.
Commun. 2004, 2770–2771.
4.10.8. 1,2,3,4-Tetrahydro-1-naphthyl acetate 24.
Analytical chiral HPLC: Chiralpac AS column, 0.46!
11. Related reactions using chiral NHCs were recently reported:
(a) Reynolds, N. T.; Read de Alaniz, J.; Rovis, T. J. Am. Chem.
Soc. 2004, 126, 9518–9519. (b) Chan, A.; Scheidt, K. A. Org.
Lett. 2005, 5, 905–908.
25 cm, hexane/2-propanol 97.5:2.5, 0.5 mL minK1
12.2 min, 15.7 min.
;
12. (a) Miyashita, A.; Matsuda, H.; Suzuki, Y.; Iwamoto, K.;
Higashino, T. Chem. Pharm. Bull. 1994, 42, 2017–2022. (b)
Miyashita, A.; Suzuki, Y.; Iwamoto, K.; Higashino, T. Chem.
Pharm. Bull. 1994, 42, 2633–2635. (c) Miyashita, A.; Suzuki,
Y.; Okumura, Y.; Higashino, T. Chem. Pharm. Bull. 1996, 44,
252–254. (d) Miyashita, A.; Suzuki, Y.; Kobayashi, M.;
Kuriyama, N.; Higashino, T. Heterocycles 1996, 43, 509–512.
(e) Miyashita, A.; Suzuki, Y.; Nagasaki, I.; Ishiguro, C.;
Iwamoto, K.; Higashino, T. Chem. Pharm. Bull. 1997, 45,
1254–1258. (f) Miyashita, A.; Obae, K.; Suzuki, Y.; Iwamoto,
K.; Oishi, E.; Higashino, T. Hetrocycles 1997, 45, 2159–2173.
(g) Miyashita, A.; Suzuki, Y.; Okumura, Y.; Iwamoto, K.;
Higashino, T. Chem. Pharm. Bull. 1998, 46, 6–11. (h)
Miyashita, A.; Suzuki, Y.; Iwamoto, K.; Higashino, T.
Chem. Pharm. Bull. 1998, 46, 390–399. (i) Miyashita, A.;
Suzuki, Y.; Iwamoto, K.; Oishi, E.; Higashino, T. Hetrocycles
1998, 49, 405–413. (j) Suzuki, Y.; Toyota, T.; Imada, F.; Sato,
M.; Miyashita, A. Chem. Commun. 2003, 1314–1315.
13. For general reviews, see: (a) Spivey, A. C.; Maddaford, A.;
Redgrave, A. J. Org. Prep. Proced. Int. 2000, 331, 333–365.
(b) Robinson, D. E. J. E.; Bull, S. D. Tetrahedron: Asymmetry
2003, 14, 1407–1446.
4.10.9. 1-(1-Naphthyl)ethyl propionate. Analytical chiral
HPLC: Chiralcel OD column, 0.46!25 cm, hexane/
2-propanol 9:1, 0.5 mL minK1; R, 9.7 min, S, 11.3 min.
4.10.10. 1-(1-Naphthyl)ethyl butyrate. Analytical chiral
HPLC: Chiralcel OD–H column, 0.46!15 cm, hexane/
2-propanol 98:2, 1 mL minK1; R, 3.4 min, S, 4.2 min.
4.10.11. 1-(1-Naphthyl)ethyl benzoate. Analytical chiral
HPLC: Chiralpac AD-H column, 0.46!15 cm, hexane/
2-propanol 98:2, 1 mL minK1; R, 5.6 min, S, 7.0 min.
References and notes
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20. Resolution of racemic amines using a chiral cyclophane will
be published later.