Kinetic resolution of racemic alcohols catalyzed by minimal artificial acylases derived from l-histidine

Article abstract of DOI:10.1016/j.tet.2007.02.020

The artificial acylases, tert-butyldiphenylsilyl ether and tris(trimethylsilyl)silyl ether of N(π)-methyl-N(α)-(2,4,6-triisopropylbenzenesulfonyl)-l-histidinol, are simple and small molecules, which contain only one chiral carbon center that originates from natural l-histidine. Asymmetric acylation of racemic secondary alcohols with isobutyric anhydride induced by these artificial acylases gave optically active isobutyrates and optically active alcohols with an S(k_{fast-reacting enantiomer}/k_{slow-reacting enantiomer}) value of up to 132. One hydrogen bonding interaction between a sulfonamidyl group of the catalysts and a substrate should be essential for inducing the high level of kinetic resolution through catalytic asymmetric acylation. Furthermore, a reusable polystyrene-bound artificial acylase was developed to examine its practicality.

Full text of DOI:10.1016/j.tet.2007.02.020

Tetrahedron 63 (2007) 6191–6203
Kinetic resolution of racemic alcohols catalyzed by minimal
artificial acylases derived from L-histidine
Yuji Kosugi,a Matsujiro Akakurab and Kazuaki Ishiharaa,
*
aGraduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan
bDepartment of Chemistry, Aichi University of Education, Igaya-cho, Kariya, 448-8542, Japan
Received 29 December 2006; accepted 6 February 2007
Available online 9 February 2007
Abstract—The artificial acylases, tert-butyldiphenylsilyl ether and tris(trimethylsilyl)silyl ether of N(p)-methyl-N(a)-(2,4,6-triisopropyl-
benzenesulfonyl)-L-histidinol, are simple and small molecules, which contain only one chiral carbon center that originates from natural L-his-
tidine. Asymmetric acylation of racemic secondary alcohols with isobutyric anhydride induced by these artificial acylases gave optically
active isobutyrates and optically active alcohols with an S(kfast-reacting enantiomer/kslow-reacting enantiomer) value of up to 132. One hydrogen bond-
ing interaction between a sulfonamidyl group of the catalysts and a substrate should be essential for inducing the high level of kinetic reso-
lution through catalytic asymmetric acylation. Furthermore, a reusable polystyrene-bound artificial acylase was developed to examine its
practicality.
Ó 2007 Elsevier Ltd. All rights reserved.
i-Pr
i-Pr
i-Pr
1. Introduction
O2
S
O2
S
i-Pr
i-Pr
N
N
N
N
NH
NH
The kinetic resolution of racemic secondary alcohols
through catalytic asymmetric acylation is a convenient and
powerful method for obtaining optically active alcohols,
which are useful as chiral building blocks for the synthesis
of pharmaceutical and natural compounds.1 Enzymatic
kinetic resolution has been established as one of the most
effective methods.2 Several impressive examples of the non-
enzymatic kinetic resolution of racemic alcohols with achi-
ral anhydrides have been reported using nucleophilic chiral
analogues of trialkylphosphine,3 4-(dimethylamino)pyridine
(DMAP),4 1-alkylimidazole (1-alkyl-IMD),5 and bicyclic
amidines and bicyclic isothioureas.6 In particular, Miller’s
biomimetic approach5 to the identification of artificial
acylases based on b-turn peptide fragments with defined sec-
ondary structures that contain 1-alkyl-IMD residues promp-
ted our present study. Very recently, we reported the rational
design of an L-histidine-derived minimal artificial acylases
1c and 3 (Fig. 1).7 The artificial acylase 1c is a simple and
small molecule (molecular weight¼660) that contains only
one chiral carbon center that originates from natural L-histi-
dine. Furthermore, reusable polystyrene-bound catalyst 3
has been developed to evaluate the practicality of 1c. In
this paper, we describe the details of the rational design
of L-histidine-derived sulfonamide catalysts for asymmetric
i-Pr
Me
Me
t-Bu
O
Me3Si
O
Si
Si
Me3Si SiMe3
Ph Ph
2a
1c
i-Pr
O2
i-Pr
S
N
N
NH
i-Pr
Me
O
Si
i-Pr i-Pr
3
Figure 1. Homo- and heterogeneous artificial acylases 1c, 2a, and 3.
acylation of racemic alcohols. In addition, we report that a
more bulky tris(trimethylsilyl)silyl [(Me3Si)3Si] ether (2a)
of N(p)-methyl-N-(2,4,6-triisopropylbenzenesulfonyl)-
L-histidinol is superior than 1c for the asymmetric induction.
2. Results and discussion
Initially, the catalytic activity of dimethylimidazole
(Me2-IMD) in the acetylation of L-menthol with acetic
anhydride was investigated (Table 1). 1,5-Me2-IMD was nu-
cleophilically the most active catalyst among 1,2-, 1,4-, and
1,5-Me2-IMD and 1-Me-IMD, although it was less active
Keywords: Asymmetric acylation; Organocatalyst; Histidine; Nucleophilic
catalyst; Kinetic resolution.
* Corresponding author. Tel.: +81 52 789 3331; fax: +81 52 789 3222;
e-mail: ishihara@cc.nagoya-u.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.020

6192
Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
Brønsted acid
Table 1. Comparison of the catalytic activities of bases for the acetylation of
L-menthol with acetic anhydridea
nucleophilic
Lewis base
O2
S
N
4
N
5
Ar
H
(x mol%)
N
N
N
two steps
NH2
N
OH
Ac2O
OAc
N
Me
i-Pr2NEt, MeCN, rt
i-Pr
i-Pr
Me
OH
O
R3Si
µx
4
N
N
µ
µy
Time (h) Yield (%) [m]b (D) [mx]b (D)
1a: Ar = C6H5, R3Si = t-BuPh2Si
1b: Ar = p-(CF3)C6H4, R3Si = t-BuPh2Si
1c: Ar = 2,4,6-i-Pr3C6H2, R3Si = t-BuPh2Si
2a: Ar = 2,4,6-i-Pr3C6H2, R3Si = (Me3Si)3Si
2b: Ar = 2,6-Ph2C6H3, R3Si = (Me3Si)3Si
2c: Ar = 3,5-(CF3)2C6H3, R3Si = (Me3Si)3Si
2d: Ar = 2,4,6-(CF3)3C6H2, R3Si = (Me3Si)3Si
Catalyst
DMAP
1,5-Me2-IMD
1,5-Me2-IMD
1-Me-IMD
X
5
5
5
0.5
0.5
3.0
100
47
100
73
29
23
4.84
4.46
4.46
4.27
3.87
4.11
4.83
4.26
4.26
3.93
3.61
3.58
10 3.0
1,4-Me2-IMD 10 3.0
1,2-Me2-IMD 10 3.0
i-Pr
O
O2
H
i-Pr
S
Y
N
N
N
N
a
Ph
Si
N
N
Unless otherwise noted, L-menthol (1 mmol), Ac2O (1.5 mmol), i-Pr2EtN
(1.5 mmol), and MeCN (2 mL) were used.
m¼mx+my, dipole moment of catalyst. [m] was calculated at the B3LYP/
i-Pr
b
Me
Me
O
O
t-Bu
O
6-311++G(d,p) level.
Ph Ph
i-Pr
5a: Y = H
than DMAP. The catalytic activity increased in proportion to
the intensity of the dipole moment (mx) on the x-axis parallel
to a lone pair at the 3-position. Thus, Miller’s L-histidine-
derived peptide was determined to be suitable as an arti-
ficial acylase.
6
5b: Y = COi-Pr
Scheme 1. Preparation of artificial acylases 1, 2, 5, and 6 derived from 4.
Table 2. Kinetic resolution of (ꢀ)-7aa
Our initial considerations for the design of new artificial acyl-
ases focused on two functional groups derived from L-histi-
dine: (i) a 1,5-dialkyl-IMD component as a nucleophilic
catalytic moiety and (ii) an amide component as a hydrogen
bonding domain.5 Thus, sulfonamides 1, 2, 5, and carbox-
amide 6 were prepared from N(p)-methyl-L-histidinol (4)8
in two steps (Scheme 1).
Me2N
O
1, 5 or 6 (5 mol%)
(i-PrCO)2O (0.5 equiv)
O
i-Pr2NEt (0.5 equiv)
toluene, rt, 3 h
OH
( )-7a
Me2N
Me2N
Compounds 1, 5, and 6 were evaluated as catalysts for the
kinetic resolution of (ꢀ)-cis-1-[p-(dimethylamino)benzoyl-
oxy]-2-cyclohexanol (7a) with (i-PrCO)2O.4c Reactions
were allowed to proceed for 3 h at room temperature in
toluene using 5 mol % of catalyst based on 7a. As shown
in Table 2, all of the L-histidine-derived catalysts examined
resulted in the preferential acylation of (1R,2S)-7a. When
sulfonamide 1c bearing two sterically bulky groups, 2,4,6-
triisopropylbenzenesulfonyl group and tert-butyldiphenyl-
silyl group, was used, (1R,2S)-8a was obtained in 47%
conversion with 83% ee (S¼24) (entry 6). The use of sulfon-
amide 1a gave (1R,2S)-7a much more selectively and rap-
idly than carboxamide 6 (entry 1 vs entry 2). In addition,
higher asymmetric induction was observed with the use of
a more acidic sulfonamide catalyst such as 1b (entry 2 vs
entry 3). In contrast, aprotic catalyst 5b was less active
and showed almost no selectivity (S¼1) (entry 4 vs entry
5). These results suggest that hydrogen bonding between
sulfonamide 1 and (1R,2S)-7a may be a key interaction for
attaining a high level of kinetic resolution.
O
O
O
O
1
2
1
2
OH
OCOi-Pr
(1S,2R)-7a
(1R,2S)-8a
Entry Catalyst Conv.b (%) ee of 7ac (%) ee of 8ac (%) Sd
1
2
3
4
5
6
6
36
51
42
48
30
47
3
60
52
70
3
5
57
71
77
7
1
7
10
16
1
1a
1b
5a
5b
1c
74
83
24
a
Unless otherwise noted, (ꢀ)-7a (1 equiv), (i-PrCO)2O (0.5 equiv),
i-Pr2EtN (0.5 equiv), catalyst (5 mol %), and toluene (2 mL) were used.
Conversion (%)¼100ꢁ(ee of 6)/(ee of 7+ee of 8).
b
c
d
HPLC analysis.
Selectivity factor¼S(kfast-reacting enantiomer/kslow-reacting enantiomer), see Ref. 9.
87 by using 7c in place of 7a (entry 8). In addition, CCl4
and toluene were more suitable solvents, probably because
less polar solvents did not inhibit hydrogen bonding interac-
tion (entries 1–5).
If hydrogen bonding between 1d and 7a is truly a key inter-
action, cis-cyclohexan-1,2-diol monoprotected by a more
electron-donating group should give better results than 7a.
As shown in Table 3, carbamates 7b and 7c were more effec-
tive than 7a (entries 5–8). In particular, the S value for the
kinetic resolution of (ꢀ)-7 was dramatically increased to
To explore the generality and scope of the 1c-induced kinetic
resolution of (ꢀ)-secondary alcohols, the acylation of several

Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
6193
Table 3. Screening of protecting groups (R) in (ꢀ)-7 and solvent effect on the kinetic resolution of (ꢀ)-7 induced by 1ca
1c (5 mol%)
OCOR
OCOR
OCOR
(i-PrCO)2O (0.5 equiv)
1
2
1
2
i-Pr2NEt (0.5 equiv)
OH
OH
OCOi-Pr
solvent, 3 h
( )-7
(1S,2R)-7
Conv.b (%)
(1R,2S)-8
ee of 7c (%)
Entry
Alcohol
R
Solvent
CH3CN
THF
CH2Cl2
Toluene
CCl4
CCl4
CCl4
CCl4
Temp (ꢃC)
ee of 8c (%)
Sd
1
2
3
4
7a
7a
7a
7a
7a
7b
7b
7c
p-(Me2N)C6H4
p-(Me2N)C6H4
p-(Me2N)C6H4
p-(Me2N)C6H4
p-(Me2N)C6H4
Me2N
rt
rt
rt
rt
rt
rt
0
30
39
43
47
49
53
54
52
25
38
66
74
81
96
99
97
57
59
50
83
83
83
83
90
5
6
8
24
27
42
64
87
5
6
7e
8e
Me2N
(CH2CH2)2N
0
a
See footnote a in Table 2.
Conversion (%)¼100ꢁ(ee of 6)/(ee of 7+ee of 8).
b
c
d
e
HPLC analysis.
Selectivity factor¼S(kfast-reacting enantiomer/kslow-reacting enantiomer), see Ref. 9.
The reaction was carried out at 0 ꢃC for 3 h.
structurally diverse alcohols with (i-PrCO)2O was examined
(Table 4). Although the acylation of trans-2-phenyl-1-cyclo-
hexanol (9), which does not have any proton accepting
groups except for 1-hydroxy group, was not selective, the ac-
ylations of not only cyclic 1,2-diol derivatives 7c, 10, and 11
butalso acyclic12gave Svalues greater than 68. In particular,
the S value was up to 132 when the reaction was conducted
at ꢂ20 ꢃC in cis-1,2-dihydroxycyclopentane derivative 10.
b-Hydroxycarboxylic acid derivatives 13 and 14 and amino
alcohol derivatives 15–18 were also suitable substrates.
regard to the kinetic resolution of (ꢀ)-14 (Table 5). The tris-
(trimethylsilyl)silyl [(Me3Si)3Si] group was a more bulky
hydroxyl protecting group than a t-BuPh2Si group, and
when 2a bearing (Me3Si)3Si group was used instead of 1c,
(ꢂ)-14 was obtained in 52% conversion with 92% ee
(S¼45) (entry 1 vs entry 2). However, more bulky catalyst
2b was not induced (ꢂ)-14 (S¼21) (entry 3). More acidic
sulfonamide catalysts 2c and 2d also showed moderate
selectivity (S¼8) (entries 4 and 5). Therefore, the balance
between the acidity of a sulfonamide and the basicity of
an imidazole seems to be important for attaining high
enantioselectivity for the kinetic resolution of racemic
alcohols.
Furthermore, catalyst 1c was improved by altering its
t-BuPh2Si group. Compounds 2a–d were evaluated with
Table 4. Kinetic resolution of racemic alcohols 7c, 9–18 [R¼(CH2CH2)2N]
induced by 1ca
Table 4. (continued)
Entry
Alcohol
Conv.b ee of recov. ee of acyl.
(%)
Sd
51
15
Entry
Alcohol
Conv.b ee of recov. ee of acyl.
(%)
Sd
alcoholc (%) productc (%)
alcoholc (%) productc (%)
ROC
NH
Ph
15
9g
42
67 (1S,2R)
51 (2R,3R)
93 (1R,2S)
80 (2S,3S)
9
1e
43
10
13
1
OH
OH
ROC
OCOR
MeO2C
i-Pr
NH
7c
2e
3e
4f
52
49
41
97 (1S,2R)
90 (1R,2S)
87
93
16
10h
11e
39
OH
OH
OCOR
90
67
94
97
10
10
ROC
132
NH
OH
17
50
53
88 (S)
86 (R)
39
17
OH
COR
O
ROC
11
5e
50
93
92
83
Ph
NH
12i
83
74
18
OH
OH
OCOR
a
12
13
6e
7e
47
44
82
93
68
19
See footnote a in Table 2.
Conversion (%)¼100ꢁ(ee of recovered alcohol)/(ee of recovered
b
OH
alcohol+ee of acylated product).
HPLC analysis.
COR
c
d
Selectivity factor¼S(kfast-reacting enantiomer/kslow-reacting enantiomer), see
64 (S)
82 (R)
Ph
Ph
OH
Ref. 9.
e
f
0 ꢃC, 3 h; CCl4.
COR
ꢂ20 ꢃC, 3 h; CCl4.
14
8e
49
80
82
25
0 ꢃC, 3 h; CHCl3–CCl4 (2:3).
0 ꢃC, 4 h; CHCl3–CCl4 (1:5).
0 ꢃC, 3 h; CHCl3–CCl4 (2:5).
g
h
i
OH
(continued)

6194
Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
Table 5. Kinetic resolution of (ꢀ)-14 induced by 1c or 2a
N
N
1c or 2 (5 mol%)
(i-PrCO)2O (0.5 equiv)
N
2.525 Å
N
O
O
O
i-Pr2NEt (0.5 equiv)
CCl4, 0 °C, 3 h
2.534 Å
Ph
OH
( )-14
N
conformer I
N
O
N
O
4.60 kJ mol-1
Ph
OCOi-Pr
(+)-19
Ph
OH
conformer II
(–)-14
Figure 3. The conformers I and II of 3-acetyl-1,5-dimethylimidazolium
cation.
Entry Catalyst Conv.b (%) ee of 14c (%) ee of 19c (%) Sd
1
2
3
4
5
1c
2a
2b
2c
2d
49
52
47
36
44
80
92
72
39
53
82
86
82
69
66
25
45
21
8
from 1c, (1R,2S)-7c, and (i-PrCO)2O was proposed based
on this X-ray structure (Fig. 2). The conformation of the
acyl group in the acylammonium salt generated from 1c and
(i-PrCO)2O would be fixed by the attractive electrostatic
interaction between its acyl oxygen and imidazoyl-2-
proton or the dipole-minimization effect. This electrostatic
interaction was expected by the results of calculation at the
B3LYP/6-311++G(d,p) level for 3-acetyl-1,5-dimethylimid-
azolium cation (Fig. 3).10,11 The calculations show that the
attractive interaction between an acyl oxygen and an imid-
azoyl proton in conformer II is stronger than that in con-
former I. Hydrogen bonding between the sulfonylamino
proton of acylammonium salt and the carbamoyl oxygen of
7c preferentially promotes the acylation of (1R,2S)-7c by a
proximity effect. On the other hand, similar hydrogen
bonding with (1S,2R)-7c inhibits its acylation.
8
a
b
c
d
See footnote a in Table 2.
Conversion (%)¼100ꢁ(ee of 14)/(ee of 14+ee of 19).
HPLC analysis.
Selectivity factor¼S(kfast-reacting enantiomer/kslow-reacting enantiomer), see Ref. 9.
According to an X-ray structural analysis, a N–H bond and
IMD ring in 1c are parallel to each other on the same side,
probably due to steric limitations imposed by the two bulky
substituents (Fig. 2). A transition-state assembly formed
Polymer-bound catalyst 3 was easily prepared from com-
mercially available resin 2012 and N(p)-methyl-N-(2,4,6-
triisopropylbenzenesulfonyl)-L-histidinol 21 (Scheme 2).4h
OMe
Si
i-Pr i-Pr
20 (1.40 mmol/g)
i-Pr
O2
i-Pr
S
N
N
NH
2.
1. TfOH
i-Pr
Me
OH
21
i-Pr
i-Pr
H
SO2
N
H
H
O2
S
N
H
H
i-Pr
H
O
N
N
O
N
O
NH
H
N
+
H
i-Pr
t-Bu
OH
Si
Me
O
O
Si
i-Pr i-Pr
i-Pr
Figure 2. ORTEP plot of 1c and a proposed transition-state assembly. The
crystal structure of 1c is drawn with 50% probability, and hydrogen atoms
except for the SO2NH moiety are omitted for clarity.
3 (0.824 mmol/g)
Scheme 2. Preparation of polystyrene resin-bound catalyst 3.

Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
6195
Table 6. Recycling of catalyst 3 in the kinetic resolution of (ꢀ)-7aa
chiral column of Daicel CHIRALCEL OD-H (4.6 mmꢁ
25 cm), AD-H (4.6 mmꢁ25 cm), or Daicel CHIRALPAK
AS-H (4.6 mmꢁ25 cm). Optical rotations were measured
on a RUDOLPH AUTOPOL IV digital polarimeter. GC
analysis was performed with Shimadzu 17A instruments
using TCI CHIRALDEX g-TA (0.25 mm I.D.ꢁ20 mꢁ
0.125 mm). Melting points were determined using a Yanaco
MP-J3. All experiments were carried out under an atmo-
sphere of dry nitrogen. For thin-layer chromatography
(TLC) analysis throughout this work, Merck precoated
TLC plates (silica gel 60 GF254 0.25 mm or silica gel NH2
F254S 0.25 mm) were used. The products were purified by
column chromatography on silica gel (E. Merck Art. 9385
or Fuji Silysia Chemical Ltd., CromatorexÒ NH-DM1020).
Microanalyses were performed at the Graduate School of
Agriculture, Nagoya University. High resolution mass spec-
tral analysis (HRMS) was performed at Chemical Instrument
Center, Nagoya University. In experiments that required dry
solvent, ether, N,N-dimethylformamide (DMF), and tetra-
hydrofuran (THF) were purchased from Aldrich or Wako
as the ‘anhydrous’ and stored over 4A molecular sieves.
Benzene, hexane, toluene, and dichloromethane were freshly
distilled from calcium hydride. Other simple chemicals were
of analytical-grade and obtained commercially.
Me2N
O
3 (5 mol%)
(i-PrCO)2O (0.5 equiv)
O
i-Pr2NEt (0.5 equiv)
toluene, rt
OH
shaking, 6 h
( )-7a
Me2N
Me2N
O
O
O
O
1
2
1
2
OH
OCOi-Pr
(1S,2R)-7a
(1R,2S)-8a
Run
Conv.b (%)
ee of 7ac (%)
ee of 8ac (%)
Sd
1
2
3
4
5
44
43
44
42
42
82
84
84
86
86
64
62
65
62
62
20
21
23
25
26
a
See footnote a in Table 2.
Conversion (%)¼100ꢁ(ee of 7)/(ee of 7+ee of 8).
b
c
d
HPLC analysis.
Selectivity factor¼S(kfast-reacting enantiomer/kslow-reacting enantiomer), see Ref. 9.
4.2. General procedure for the preparation
of N(p)-methyl-N(a)-arenesulfonyl-L-histidinol
Compound 3 (5 mol %) was reused more than five times for
the acylation of (ꢀ)-7a (1 equiv) with (i-PrCO)2O
(0.5 equiv) under shaking at room temperature in toluene
for 6 h in the presence of i-Pr2EtN (0.5 equiv) without any
loss of activity or selectivity (Table 6).
To a solution of 48 (4.0 mmol) in pyridine (20 mL) was added
the corresponding arenesulfonyl chloride (5.5 mmol) at
0 ꢃC. After the mixture was stirred for 5 h at room tempera-
ture, the solvent was removed under reduced pressure. The
crude product was dissolved in EtOAc and washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, and concentrated under reduced pressure. The
residue was purified by flash column chromatography on
CromatorexÒ NH-DM1020 (eluent: EtOAc) to give N(p)-
methyl-N(a)-(arenesulfonyl)-L-histidinol in good yield. The
corresponding physical and spectroscopic data for com-
pounds follow.
3. Conclusion
In summary, we have designed minimal artificial acylases 1c
and 2a derived from L-histidine by introducing a sulfonyl-
amino group in place of a polypeptide chain based on the
notion that sulfonamide hydrogen bonding is much stronger
than the corresponding carboxamide interaction. In addition,
we developed a reusable organocatalyst 3, which should
greatly contribute to green and sustainable chemistry.
4.2.1. (D)-N(p)-Methyl-N(a)-benzenesulfonyl-L-histidi-
nol. TLC (silica gel NH2 F254S, EtOAc–MeOH¼11:1)
Rf ¼0.25; purification by column chromatography on Cro-
matorexÒ NH-DM1020 (EtOAc–MeOH¼10:1); [a]2D0 6.0
(c 1.06, CHCl3); IR (KBr) 3600–3250, 2924, 1636, 1510,
4. Experimental
4.1. General
1447, 1324, 1158, 1093, 690, 592 cmꢂ1
;
1H NMR
(300 MHz, CDCl3) d 2.75 (dd, J¼6.0, 15.3 Hz, 1H), 2.88
(dd, J¼7.5, 15.3 Hz, 1H), 3.32–3.38 (m, 1H), 3.39 (s, 3H),
3.49 (d, J¼4.2 Hz, 2H), 4.48–4.95 (br, 1H), 6.61 (s, 1H),
7.26 (s, 1H), 7.42 (t, J¼7.4 Hz, 2H), 7.51 (t, J¼7.4 Hz,
1H), 7.77 (d, J¼7.4 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d 25.9, 31.4, 54.3, 62.3, 126.7 (2C), 127.4, 127.9, 129.0
(2C), 132.4, 137.8, 140.5. Anal. Calcd for C13H17N3O3S:
C, 52.86; H, 5.80. Found: C, 52.81; H, 5.82.
Infrared (IR) spectra were recorded on a Jasco FT/IR 460
plus spectrometer. H NMR spectra were measured on a
1
Varian Gemini-2000 spectrometer (300 MHz) at ambient
temperature. Data were recorded as follows: chemical
shift in parts per million from internal tetramethylsilane on
the d scale, multiplicity (s¼singlet; d¼doublet; t¼triplet;
m¼multiplet), coupling constant (Hz), integration, and
assignment. 13C NMR spectra were measured on Varian
Gemini-2000 (75 MHz) spectrometer. Chemical shifts were
recorded in parts per million from the solvent resonance
employed as the internal standard (deuterochloroform at
77.00 ppm). High performance liquid chromatography
(HPLC) analysis was conducted using Shimadzu LC-10
AD coupled diode array-detector SPD-MA-10A-VP and
4.2.2. N(p)-Methyl-N(a)-(4-trifluoromethylbenzenesul-
fonyl)-L-histidinol. 1H NMR (300 MHz, CDCl3) d 2.84
(dd, J¼6.0, 15.3 Hz, 1H), 2.92 (dd, J¼7.1, 15.5 Hz, 1H),
3.41 (m, 1H), 3.49 (s, 3H), 3.54 (d, J¼4.2 Hz, 2H), 6.02 (br,
1H), 6.60 (s, 1H), 7.28 (s, 1H), 7.67 (d, J¼8.1 Hz, 2H), 7.93
(d, J¼8.4 Hz, 2H). Anal. Calcd for C14H16F3N3O3S: C,
46.28; H, 4.44. Found: C, 46.33; H, 4.41.

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Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
4.2.3. (D)-N(p)-Methyl-N(a)-(2,4,6-triisopropylbenz-
enesulfonyl)-L-histidinol (21). White solid (838 mg,
2.0 mmol, 50% yield); [a]2D0 20.4 (c 1.0, CHCl3); IR (KBr)
3486, 3114, 3053, 2958, 2928, 2869, 1601, 1461, 1316,
133.9 (q, J¼33.0 Hz), 135.4 (4C), 134.0, 144.1. Anal. Calcd
for C30H34F3N3O3SSi: C, 59.88; H, 5.69. Found: C, 59.83;
H, 5.73.
1
1294, 1146, 1113, 1059, 1041, 664, 561 cmꢂ1; H NMR
4.3.3. (S)-(D)-1-tert-Butyldiphenylsilyloxy-3-(30-methyl-
30H-imidazol-40-yl)-2-(200,400,600-triisopropylbenzenesul-
fonylamino)propane (1c). White solid (615 mg,
(300 MHz, CDCl3) d 1.248 (d, J¼6.9 Hz, 12H), 1.255 (d,
J¼6.9 Hz, 6H), 2.75–3.02 (m, 3H), 3.42–3.52 (m, 3H),
3.53 (s, 3H), 4.13 (septet, J¼6.9 Hz, 2H), 5.72 (d,
J¼6.6 Hz, 1H), 6.58 (s, 1H), 7.16 (s, 2H), 7.27 (s, 1H);
13C NMR (75 MHz, CDCl3) d 23.6, 24.9, 25.0, 26.2, 29.8,
31.5, 34.1, 53.7, 61.4, 123.8, 127.5, 128.1, 133.3, 137.7,
150.1, 152.8; MS (FAB+) [M+H]+ m/z 422. Anal. Calcd
for C22H35N3O3S: C, 62.67; H, 8.37. Found: C, 62.61;
H, 8.39.
1
0.93 mmol, 98% yield); [a]2D0 4.8 (c 1.0, CHCl3); H NMR
(300 MHz, CDCl3) d 1.05 (s, 9H), 1.20 (d, J¼6.9 Hz, 6H),
1.23 (d, J¼6.9 Hz, 6H), 1.25 (d, J¼6.9 Hz, 6H), 2.80–3.02
(m, 3H), 3.43 (s, 3H), 3.61 (br s, 3H), 4.10 (septet,
J¼6.9 Hz, 2H), 4.95–5.15 (br, 1H), 6.48 (s, 1H), 7.08 (s,
2H), 7.26–7.44 (m, 8H), 7.52–7.68 (m, 5H); 13C NMR
(75 MHz, CDCl3) d 19.3, 23.6, 24.9, 26.2, 27.0, 29.8, 31.3,
34.2, 53.3, 63.6, 123.8, 127.3, 127.9, 128.0, 130.0, 130.1,
132.5, 132.6, 133.4, 135.47, 135.50, 138.0, 150.1, 152.9;
IR (KBr) 4325, 3072, 3053, 2959, 2928, 2859, 2739, 1601,
1511, 1463, 1427, 1322, 1152, 1113, 1072, 741, 703, 661,
560, 506 cmꢂ1; MS (FAB+) [M+H]+ m/z 660. Anal. Calcd
for C38H53N3O3SSi: C, 69.15; H, 8.09. Found: C, 69.19;
H, 8.03.
4.3. General procedure for the preparation of (S)-1-tert-
butyldiphenylsilyloxy-3-(30-methyl-30H-imidazol-40-yl)-
2-(arenesulfonylamino)propane (1)
To a solution of N(p)-methyl-N(a)-arenesulfonyl-L-histi-
dinol (0.95 mmol) in DMF (5 mL) were added tert-butyl-
chlorodiphenylsilane (304 mL, 1.17 mmol) and imidazole
(163 mg, 2.4 mmol) at 0 ꢃC. After the mixture was stirred
for 6 h at room temperature, the solvent was removed under
reduced pressure to give the crude product. The residue was
purified by flash column chromatography on NH silica gel
(eluent: hexane–EtOAc¼1:1) to give 1 in good yield. The
corresponding physical and spectroscopic data for 1 follow.
4.4. Preparation of (S)-1-tris(trimethylsilyl)silyloxy-3-
(1-methyl-1H-imidazol-5-yl)propan-2-amine
To a solution of 48 (2.0 mmol) and Et3N (976 mL, 7.0 mmol)
in DMF (8 mL) was added chlorotris(trimethylsilyl)silane
(1.98 mg, 7.0 mmol) at 0 ꢃC. The mixture was then stirred
for 24 h at room temperature, diluted with CHCl3, washed
with water, and extracted with CHCl3. The organic layer
was dried over Na2SO4 and evaporated. The residue was
purified by flash column chromatography on NH silica gel
(eluent: EtOAc–MeOH¼50:1) to give 559 mg (69% yield)
4.3.1. (D)-(S)-1-tert-Butyldiphenylsilyloxy-3-(30-methyl-
30H-imidazol-40-yl)-2-(benzenesulfonylamino)propane
(1a). TLC (silica gel NH2 F254S, hexane–EtOAc¼1:2)
Rf¼0.15; purification by column chromatography on Cro-
matorexÒ NH-DM1020 (hexane–EtOAc¼1:2–1:4); [a]2D0
2.34 (c 0.51, CHCl3); IR (KBr) 3069, 2930, 2857, 1509,
1
of product as a colorless oil. H NMR (300 MHz, CDCl3)
d 0.19 (s, 27H), 2.46 (dd, J¼8.3, 14.9 Hz, 1H), 2.74 (dd,
J¼5.0, 14.9 Hz, 1H), 2.94–3.04 (m, 1H), 3.38 (dd, J¼1.5,
5.4 Hz, 2H), 3.56 (s, 3H), 6.84 (s, 1H), 7.39 (s, 1H).
1
1428, 1324, 1158, 1113, 1070, 823, 706, 588 cmꢂ1; H
NMR (300 MHz, CDCl3) d 1.04 (s, 9H), 2.84 (dd, J¼5.4,
15.0 Hz, 1H), 2.96 (dd, J¼7.8, 15.0 Hz, 1H), 3.28–3.37
(m, 1H), 3.41 (s, 3H), 3.44 (dd, J¼4.8, 10.5 Hz, 1H), 3.59
(dd, J¼3.9, 10.5 Hz, 1H), 5.42 (br, 1H), 6.54 (s, 1H), 7.25
(s, 1H), 7.34–7.58 (m, 13H), 7.66 (d, J¼8.1 Hz, 2H); 13C
NMR (75 MHz, CDCl3) d 19.2, 26.4, 26.9 (3C), 31.3,
53.8, 63.7, 126.7 (2C), 127.0, 127.9 (4C), 128.0, 129.0
(2C), 130.0 (2C), 132.5 (2C), 135.4 (4C), 138.0 (2C),
140.1. Anal. Calcd for C29H35N3O3SSi: C, 65.26; H, 6.61.
Found: C, 65.18; H, 6.66.
4.5. General procedure for the preparation of arene-
sulfonyl chlorides
To
a
solution of 2,6-diphenyliodobenzene14 (1.42 g,
4 mmol) or 1,3,5-tris(trifluoromethyl)benzene (0.746 mL,
4 mmol) in Et2O was added dropwise BuLi (2.56 mL,
1.56 M in hexane, 4 mmol) at 0 ꢃC. The mixture turned
yellow and a white solid precipitated. After the mixture
was stirred for 8 h at room temperature, the freshly distilled
sulfuryl chloride (0.643 mL, 8 mmol) was added slowly at
ꢂ78 ꢃC. The mixture was stirred overnight at room temper-
ature, cooled to 0 ꢃC, poured onto 1 M HCl, and extracted
with Et2O. The organic layer was washed with water and
brine, dried over MgSO4, filtered, and concentrated under re-
duced pressure. The residue was recrystallized from CHCl3–
hexane to give the corresponding arenesulfonyl chloride in
good or modest yield. The corresponding physical and spec-
troscopic data for arenesulfonyl chloride follow.
4.3.2. (S)-(D)-1-tert-Butyldiphenylsilyloxy-3-(30-methyl-
30H-imidazol-40-yl)-2-(400-trifluoromethylbenzenesul-
fonylamino)propane (1b). TLC (silica gel NH2 F254S
,
hexane–EtOAc¼1:2) Rf¼0.26; purification by column
chromatography on silica gel CromatorexÒ NH-DM1020
(hexane–EtOAc¼1:2–1:4) and recrystallization (CHCl3–
1
hexane); [a]2D0 1.72 (c 0.93, CHCl3); H NMR (300 MHz,
CDCl3) d 1.02 (s, 9H), 2.88 (dd, J¼6.0, 15.3 Hz, 1H), 2.98
(dd, J¼6.6, 15.3 Hz, 1H), 3.32–3.42 (m, 1H), 3.44 (s, 3H),
3.47 (dd, J¼6.0, 10.3 Hz, 1H), 3.57 (dd, J¼4.2, 10.3 Hz,
1H), 5.55 (br, 1H), 6.57 (s, 1H), 7.21 (s, 1H), 7.33–7.39
(m, 4H), 7.41–7.48 (m, 2H), 7.50–7.56 (m, 4H), 7.57 (d,
J¼8.2 Hz, 2H), 7.73 (d, J¼8.2 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 19.2, 26.2, 26.8 (3C), 31.3, 54.1, 63.9,
123.1 (q, J¼273 Hz), 126.1 (q, J¼3.7 Hz, 2C), 126.9,
127.1 (2C), 127.9 (4C), 128.1, 130.1 (2C), 132.46, 132.53,
4.5.1. 2,6-Diphenylbenzenesulfonyl chloride.13 Brown
solid (924 mg, 2.8 mmol, 70% yield); H NMR (300 MHz,
1
CDCl3) d 7.40–7.52 (m, 12H) 7.63 (dd, J¼7.5, 8.1 Hz,
1H); 13C NMR (75 MHz, CDCl3) d 128.0, 128.2, 129.0,
133.0, 133.3, 140.0, 141.7, 143.7; IR (KBr) 3443, 3049,
1574, 1446, 1385, 1191, 811, 765, 748, 701 cmꢂ1
.

Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
6197
4.5.2. 2,4,6-Tris(trifluoromethyl)benzenesulfonyl chlo-
3.51 (m, 1H), 3.55 (s, 3H), 5.30–6.04 (br, 1H), 6.65 (s,
1H), 7.28 (s, 1H), 8.05 (s, 1H), 8.24 (s, 2H); 13C NMR
(126 MHz, CDCl3) d 0.3 (9C), 26.3, 31.5, 55.0, 67.6,
122.5 (q, J¼273 Hz), 126.4, 127.0, 127.0, 128.4, 133.2 (q,
J¼34 Hz), 138.3, 144.0; IR (KBr) 3423, 3112, 2957, 2897,
HRMS(FAB) calcd for C24H42F6N3O3SSi4 [(M+H)+]
678.1928. Found: 678.1937.
1
ride.13,15 White solid (453 mg, 1.2 mmol, 30% yield); H
NMR (300 MHz, CDCl3) d 8.44 (s, 2H); 13C NMR
(126 MHz, CDCl3) d 121.6 (q, J¼277 Hz), 130.2, 133.6
(q, J¼35 Hz), 137.1 (q, J¼36 Hz), 145.4; IR (KBr) 3435,
3113, 1405, 1198, 1273, 1198, 1140, 1088, 924, 863, 712,
1626, 1422, 1353, 1281, 1165, 1144, 1077, 840 cmꢂ1
;
687 cmꢂ1
.
4.6. General procedure for the preparation of (S)-1-
tris(trimethylsilyl)silyloxy-3-(30-methyl-30H-imidazol-
40-yl)-2-(arenesulfonylamino)propane (2)
4.6.4. (S)-1-Tris(trimethylsilyl)silyloxy-3-(30-methyl-30H-
imidazol-40-yl)-2-(200,400,600-tris(trifluoromethyl)benz-
enesulfonylamino)propane (2d). White solid (140 mg,
1
To a solution of (S)-1-tris(trimethylsilyl)silyloxy-3-(1-meth-
yl-1H-imidazol-5-yl)propan-2-amine (300 mg, 0.45 mmol)
and pyridine (44.5 mL, 0.55 mmol) in CH2Cl2 (5 mL) was
added the corresponding arenesulfonyl chloride (0.55 mmol)
at 0 ꢃC. After the mixture was stirred for 24 h at room tem-
perature, the solvent was removed under reduced pressure
to give the crude product. The residue was purified by flash
column chromatography on NH silica gel (eluent: hexane–
EtOAc¼1:1) to give 2 in good yield. The corresponding
physical and spectroscopic data for 2 follow.
0.19 mmol, 42% yield); [a]2D2 ꢂ10.1 (c 1.0, CHCl3); H
NMR (300 MHz, CDCl3) d 0.15 (s, 27H), 3.84 (dd, J¼6.0,
15.0 Hz, 1H), 2.91 (dd, J¼8.6, 15.0 Hz, 1H), 3.41 (dd,
J¼3.9, 9.6 Hz, 1H), 3.54 (dd, J¼2.7, 9.6 Hz, 1H), 3.57 (s,
3H), 3.87–3.99 (m, 1H), 5.32–5.49 (br, 1H), 6.67 (s, 1H),
7.30 (s, 1H), 8.28 (s, 2H); 13C NMR (75 MHz, CDCl3)
d 0.2 (9C), 27.1, 31.3, 55.4, 67.6, 121.9 (q, J¼274 Hz),
122.2 (q, J¼275 Hz, 2C), 127.1, 128.5, 129.5, 132.0 (q,
J¼33 Hz, 2C), 134.1 (q, J¼35 Hz), 138.2, 145.7; IR (KBr)
3600–3300, 2953, 2896, 1626, 1509, 1423, 1367, 1274,
1179, 1083, 917, 838 cmꢂ1; HRMS(FAB) calcd for
C25H41F9N3O3SSi4 [(M+H)+] 746.1802. Found: 746.1814.
4.6.1. (S)-(L)-1-Tris(trimethylsilyl)silyloxy-3-(30-methyl-
30H-imidazol-40-yl)-2-(200,400,600-triisopropylbenzene-
sulfonylamino)propane (2a). White solid (597 mg,
4.7. Preparation of (S)-3-(30-methyl-30H-imidazol-40-yl)-
2-(200,400,600-triisopropylbenzenesulfonylamino)propyl
isobutyrate (5a) and (S)-2-[N-isobutyryl(20,40,60-triiso-
propylbenzenesulfonyl)amino]-3-(300-methyl-300H-imid-
azol-400-yl)-propyl isobutyrate (5b)
1
0.89 mmol, 89% yield); [a]2D2 ꢂ11.9 (c 1.1, CHCl3); H
NMR (300 MHz, CDCl3) d 0.14 (s, 27H), 1.18–1.34 (m,
18H), 2.72 (dd, J¼4.1, 15.2 Hz, 1H), (dd, J¼7.4, 22.0 Hz,
1H), 2.90 (septet, J¼6.8 Hz, 1H), 3.37 (d, J¼4.5 Hz, 2H),
3.50 (s, 3H), 3.50–3.63 (m, 1H), 4.14 (septet, J¼6.7 Hz,
2H), 4.82 (d, 9.0 Hz, 1H), 6.74 (s, 1H), 7.16 (s, 2H), 7.35
(s, 1H); 13C NMR (75 MHz, CDCl3) d 0.4 (9C), 23.7 (2C),
25.0 (2C), 25.1 (2C), 25.6, 29.8 (2C), 31.5, 34.3, 53.4,
67.4, 123.9 (2C), 127.3, 128.3, 133.5, 138.2, 150.1 (2C),
153.0; IR (KBr) 3435, 2957, 2894, 1602, 1464, 1269,
To a solution of N(p)-methyl-N(a)-200,400,600-triisopropyl-
benzenesulfonyl-L-histidinol (1 mmol) in CHCl3 (10 mL)
were added isobutyryl chloride (105 mL, 1 mmol) and
Et3N (101 mL, 1 mmol) at 0 ꢃC. After the mixture was stirred
for 6 h at room temperature, the solvent was removed under
reduced pressure. The residue was purified by flash column
chromatography on NH silica gel (eluents: EtOAc–MeOH)
to give 5a (143 mg, 0.29 mmol) and 5b (185 mg,
0.33 mmol) in respective yield of 29% and 33% as white
solids. The corresponding physical and spectroscopic data
for 5 follow.
1246, 1155, 1071, 961, 838, 744, 688, 661 cmꢂ1
;
HRMS(FAB) calcd for C31H52N3O3SSi4 [(M+H)+]
668.3589. Found: 668.3571.
4.6.2. (S)-(L)-1-Tris(trimethylsilyl)silyloxy-3-(30-meth-
yl-30H-imidazol-40-yl)-2-(200,600-diphenylbenzenesulfonyl-
amino)propane (2b). White solid (226 mg, 0.33 mmol,
41% yield); [a]2D2 ꢂ3.6 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) d 0.09 (s, 27H), 2.23 (dd, J¼5.3,
15.0 Hz, 1H), 2.50 (dd, J¼7.8, 15.0 Hz, 1H), 3.00 (dd,
J¼6.0, 9.6 Hz, 1H), 3.06 (dd, J¼4.1, 9.6 Hz, 1H), 3.32 (s,
3H), 3.10–3.42 (m, 1H), 3.60 (d, J¼8.4 Hz, 1H), 6.47 (s,
1H), 7.27 (d, J¼6.6 Hz, 2H), 7.34 (d, J¼7.8 Hz, 2H),
7.38–7.56 (m, 10H); 13C NMR (75 MHz, CDCl3) d 0.4,
25.2, 31.3, 54.4, 67.7, 127.1, 128.2, 129.5, 130.7, 132.1,
138.0, 140.4, 141.4, 142.2; IR (KBr) 3388, 3058, 2950,
1572, 1503, 1443, 1410, 1336, 1245, 1157, 1062, 838,
761, 701 cmꢂ1; HRMS(FAB) calcd for C34H52N3O3SSi4
[(M+H)+] 694.2807. Found: 694.2808.
4.7.1. (S)-(D)-5a. TLC (silica gel NH2 F254S, hexane–
1
EtOAc¼1:2) Rf¼0.22; [a]2D0 15.2 (c 1.0, CHCl3); H NMR
(300 MHz, CDCl3) d 7.33 (s, 1H), 7.15 (s, 1H), 6.70 (d,
J¼8.1 Hz, 1H), 6.45 (s, 1H), 4.17 (m, 2H), 4.05 (dd,
J¼4.7, 11.3 Hz, 1H), 3.95 (dd, J¼6.5, 11.3 Hz, 1H), 5.79
(m, 1H), 3.65 (s, 3H), 3.01 (dd, J¼8.0, 15.5 Hz, 1H), 2.90
(m, 2H), 2.15 (m, 1H), 1.24 (m, 18H), 1.04 (d, J¼7.2 Hz,
3H), 0.99 (d, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 18.76, 18.83, 23.6, 24.8, 25.0, 27.2, 29.7, 31.7, 33.5,
34.1, 51.5, 64.2, 123.8, 126.6, 128.0, 134.0, 137.9, 149.8,
152.6, 176.7; IR (KBr) 3436, 2961, 2929, 2871, 1735,
1601, 1466, 1321, 1194, 1151, 1113, 663, 570 cmꢂ1; MS
(FAB+) [M+H]+ m/z 492. Anal. Calcd for C26H41N3O4S:
C, 63.51; H, 8.40. Found: C, 63.55; H, 8.34.
4.6.3. (S)-(L)-1-Tris(trimethylsilyl)silyloxy-3-(30-methyl-
30H-imidazol-40-yl)-2-[300,500-bis(trifluoromethyl)benz-
enesulfonylamino]propane (2c). White solid (77 mg,
4.7.2. (S)-(L)-5b. TLC (silica gel NH2 F254S, hexane–
EtOAc¼1:2) Rf¼0.37; [a]2D0 ꢂ3.9 (c 1.0, CHCl3); 1H
NMR (300 MHz, CDCl3) d 7.32 (s, 1H), 7.23 (s, 2H), 6.59
(s, 1H), 4.32 (m, 3H), 3.95 (m, 2H), 3.48 (s, 3H), 3.44 (m,
2H), 2.92 (m, 1H), 2.71 (dd, J¼3.6, 15.6 Hz, 1H), 2.38 (m,
1
0.11 mmol, 69% yield); [a]2D1 ꢂ11.9 (c 0.9, CHCl3); H
NMR (300 MHz, CDCl3) d 0.13 (s, 27H), 2.80 (dd, J¼5.7,
15.3 Hz, 1H), 2.90 (dd, J¼7.2, 15.3 Hz, 1H), 3.33 (dd,
J¼5.6, 9.8 Hz, 1H), 3.42 (dd, J¼3.3, 9.8 Hz, 1H), 3.42–

6198
Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
1H), 1.26 (m, 18H), 1.12 (d, J¼6.6 Hz, 3H), 1.06 (d,
J¼1.5 Hz, 3H), 1.04 (dd, J¼1.5, 6.9 Hz, 6H); 13C NMR
(75 MHz, CDCl3) d 18.6, 18.8, 19.1, 19.6, 23.5, 24.6, 24.7,
25.9, 29.4, 31.2, 33.7, 34.2, 35.7, 57.7, 64.1, 124.4, 127.7,
128.1, 131.6, 137.9, 151.1, 154.9, 176.3, 179.3; IR (KBr)
3439, 2964, 2934, 2873, 1742, 1689, 1601, 1466, 1386,
1367, 1336, 1204, 1145, 952, 664, 588, 564 cmꢂ1; MS
(FAB+) [M+H]+ m/z 562. Anal. Calcd for C30H47N3O5S:
C, 64.14; H, 8.43. Found: C, 64.23; H, 8.51.
in quantitative yield.16 Subsequent aminolysis of cyclic
carbonates (20 mmol) with pyrrolidine (10 mL) in THF
(40 mL) under reflux conditions gave 1-(N-pyrrolidine-10-
carbonyloxy)-2-alcohols (7c, 10–12) in quantitative yield.
For spectral and analytical data of 7c, 10–12, see Sections
4.11.5, 4.11.7, 4.11.9, and 4.11.11, respectively.
4.11. General procedure for the kinetic resolution
of racemic alcohols with isobutyric anhydride
induced by nucleophilic catalysts
4.8. Preparation of (L)-N(p)-methyl-N(a)-benzoyl-
L-histidinol
To a solution of racemic alcohol (0.25 mmol) and catalyst
(0.0125 mmol) in toluene (2.5 mL) were added i-Pr2NEt
(21.8 mL, 0.125 mmol) and isobutyric anhydride (20.7 mL,
0.125 mL). After being stirred for 3 h at room temperature
or 0 ꢃC (for each reaction temperature, see Tables 2–6), the
reaction mixture was treated with 0.1 M HCl aqueous solu-
tionand extracted with EtOAc. The organiclayer was washed
with saturated aqueous NaHCO3, dried over Na2SO4, and
concentrated under reduced pressure. The ee values of the re-
covered alcohol and the acylated product were determined by
HPLC analysis of the crude products. The conversion (c) was
estimated by the following equation, c (%)¼[ee (recovered
alcohol)]/[ee (recovered alcohol)+ee (acylated product)].9
The S value was estimated by the following equation,
S¼ln[(1ꢂc)(1ꢂeealcohol)]/ln[(1ꢂc)(1+eealcohol)].9 The cor-
responding physical and spectroscopic data for the recovered
alcohols and the acylated products follow.
To a solution of 4 (621 mg, 4 mmol) in pyridine (20 mL) was
added benzoyl chloride (0.638 mL, 5.5 mmol) at 0 ꢃC. After
the mixture was stirred for 5 h at room temperature, the sol-
vent was removed under reduced pressure. The crude prod-
uct was dissolved in EtOAc and washed with water and
brine. The organic phase was dried over Na2SO4, filtered,
and concentrated under reduced pressure. The residue was
purified by flash column chromatography on NH silica gel
(eluent: EtOAc) to give N(p)-methyl-N(a)-benzoyl-L-histi-
dinol in good yield. TLC (silica gel NH2 F254S, EtOAc–
MeOH¼10:1) Rf¼0.21; [a]2D0 ꢂ28.2 (c 1.0, CHCl3); IR
(neat) 3500–3300 (br), 2923, 2852, 1638, 1542 cmꢂ1; H
1
NMR (300 MHz, CDCl3) d 2.99 (s, 1H), 3.01 (d,
J¼3.0 Hz, 1H), 3.72 (s, 3H), 3.77 (d, J¼1.5 Hz, 1H), 3.78
(d, J¼1.2 Hz, 1H), 4.23 (m, 1H), 6.77 (d, J¼7.8 Hz, 1H),
6.83 (s, 1H), 7.43 (m, 3H), 7.52 (m, 1H), 7.74 (m, 1H);
13C NMR (CDCl3) 25.0, 31.6, 50.8, 61.5, 126.9, 127.5,
128.5 (2C), 128.7, 131.6, 134.1, 137.8, 167.7. Anal. Calcd
for C14H17N3O2: C, 64.85; H, 6.61. Found: C, 64.90; H,
6.59.
4.11.1. (1S,2R)-cis-1-[p-(Dimethylamino)benzoyloxy]-2-
cyclohexanol (7a) (entry 5, Table 3).4c TLC (hexane–
EtOAc¼2:1) Rf¼0.11; 1H NMR (300 MHz, CDCl3)
d 1.34–1.52 (m, 2H), 1.60–1.78 (m, 4H), 1.84 (q,
J¼8.6 Hz, 1H), 1.99 (q, J¼9.8 Hz, 1H), 2.17 (d, J¼4.2 Hz,
1H), 3.05 (s, 6H), 3.91–3.98 (m, 1H), 5.15–5.19 (m, 1H),
6.52 (d, J¼9.1 Hz, 2H), 7.93 (d, J¼9.1 Hz, 2H); HPLC
(Daicel Chiralpak OD-H, hexane–2-propanol¼20:1, flow
rate¼1.0 mL/min) tR¼26.9 ((1R,2S), minor) and 55.5
((1S,2R), major) min. The absolute stereochemistry of 7a
was determined by comparison of its HPLC-analytical
data with the ones reported in the literatre.4c
4.9. Preparation of (S)-(D)-1-tert-butyldiphenylsilyloxy-
3-(30-methyl-30H-imidazol-40-yl)-2-benzoylamino-
propane (6)
(S)-(+)-6 was synthesized from N(p)-methyl-N(a)-benzoyl-
L-histidinol and tert-butylchlorodiphenylsilane according to
the procedure shown in Section 4.3. TLC (silica gel NH2
F254S, hexane–EtOAc¼1:2) Rf¼0.17; purification by col-
umn chromatography on silica gel CromatorexÒ NH-
DM1020 (hexane–EtOAc¼1:2–1:4); [a]2D0 15.5 (c 0.62,
4.11.2. (1R,2S)-(L)-cis-1-[p-(Dimethylamino)benzoyl-
oxy]-2-cyclohexyl isobutyrate (8a) (entry 5, Table 3).4c
TLC (hexane–EtOAc¼2:1) Rf¼0.60; [a]2D0 ꢂ48.0 (c 1.0,
CHCl3) for 8a of 83% ee; HPLC (Daicel Chiralcel OD-H,
hexane–2-propanol¼20:1, flow rate¼1.0 mL/min) tR¼9.4
((1S,2R), minor) and 12.1 ((1R,2S), major) min; IR (film)
3019, 2943, 1725, 1697, 1608, 1526, 1368, 1281, 1216,
1
CHCl3); H NMR (300 MHz, CDCl3) d 1.13 (s, 9H), 2.93
(dd, J¼5.0, 15.0 Hz, 1H), 3.05 (dd, J¼9.0, 15.0 Hz, 1H),
3.70 (s, 3H), 3.77 (dd, J¼3.6, 10.4 Hz, 1H), 3.86 (dd,
J¼2.7, 10.4 Hz, 1H), 4.20 (m, 1H), 6.64 (br, 1H), 6.66 (s,
1H), 7.42 (m, 10H), 7.64 (m, 6H); 13C NMR (75 MHz,
CDCl3) d 19.3, 25.5, 26.9 (3C), 31.4, 50.0, 63.2, 126.7
(2C), 127.87, 127.94 (4C), 128.1, 128.6 (2C), 130.0,
130.1, 131.6, 132.6, 132.9, 134.1, 135.46 (2C), 135.53
(2C), 138.1, 166.9. Anal. Calcd for C30H35N3O2Si: C,
72.40; H, 7.09. Found: C, 72.48; H, 7.06.
1
1184, 1109, 760, 668 cmꢂ1; H NMR (300 MHz, CDCl3)
d 1.15 (q, J¼3.6 Hz, 6H), 1.42–15.6 (m, 2H), 1.63–1.81
(m, 4H), 1.87–2.02 (m, 2H), 2.54 (septet, J¼6.9 Hz, 1H),
3.04 (s, 6H), 5.07–5.13 (m, 1H), 5.19–5.26 (m, 1H), 6.64
(d, J¼6.9 Hz, 2H), 7.90 (d, J¼8.7 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 18.9, 19.0, 27.79 (2C), 27.83, 27.9,
34.2, 40.0 (2C), 70.7, 71.0, 110.6 (2C), 117.2, 131.2 (2C),
153.2, 160.0, 176.3. The absolute stereochemistry of 8a
was determined by comparison of its [a]D- and HPLC-ana-
lytical data with the ones reported in the literature.4c
4.10. General procedure for the preparation of
1-(N-pyrrolidine-10-carbonyloxy)-2-alcohols
(7c, 10–12) derived from meso-1,2-diols
Treatment of meso-1,2-diols (20 mmol) with bis(trichloro-
methyl)carbonate (triphosgene) (20 mmol) in dichloro-
methane (100 mL) in the presence of pyridine (10 mL) at
room temperature gave the corresponding cyclic carbonates
4.11.3. (1S,2R)-cis-1-Dimethylcarbamoyloxy-2-cyclohex-
anol (7b) (entry 6, Table 3). TLC (hexane–EtOAc¼2:1)
Rf¼0.11; GC (CHIRALDEX g-TA (20 m), inj. temp

Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
6199
140 ꢃC, col. temp 110 ꢃC, N2 (80 Pa)) tR¼29.4 ((1R,2S)-7b,
minor), 31.6 ((1S,2R)-7b, major) min; 1H NMR (300 MHz,
CDCl3) d 1.25–1.50 (m, 2H), 1.50–1.64 (m, 2H), 1.64–1.80
(m, 3H), 1.80–1.90 (m, 1H), 2.66 (s, 1H), 2.94 (s, 3H), 2.95
(s, 3H), 3.83 (br, 1H), 4.89–4.95 (m, 1H); 13C NMR
(75 MHz, CDCl3) d 21.4, 22.0, 28.1, 29.9, 35.9, 36.4, 70.2,
74.6, 156.8. Anal. Calcd for C9H17NO3: C, 57.73; H, 9.15.
Found: C, 57.78; H, 9.22. The absolute stereochemistry of
7b was determined by analogy with that of 7a.
4.11.8. (L)-cis-1-(N-Pyrrolidine-10-carbonyloxy)-2-
cyclopentyl isobutyrate (entry 3, Table 4).4c TLC (hex-
ane–EtOAc¼2:1) Rf ¼0.28; [a]2D0 ꢂ32.4 (c 1.0, CHCl3) for
94% ee; HPLC (Daicel Chiralpak AS-H, hexane–2-prop-
anol¼20:1, flow rate¼1.0 mL/min) tR¼8.6 (major) and
10.2 (minor) min; IR (KBr) 2973, 2876, 1736, 1708, 1419,
1345, 1198, 1155, 1128, 1109, 767 cmꢂ1
;
1H NMR
(300 MHz, CDCl3) d 1.15 (d, J¼1.8 Hz, 3H), 1.17 (d,
J¼1.8 Hz, 3H), 1.56–1.72 (m, 1H), 1.72–1.80 (m, 1H),
1.80–1.92 (m, 6H), 1.92–2.06 (m, 2H), 2.53 (septet,
J¼6.9 Hz, 1H), 3.31 (t, J¼6.3 Hz, 2H), 3.37 (t, J¼6.3 Hz,
2H), 5.08 (dt, J¼4.2, 6.0 Hz, 1H), 5.15 (dt, J¼4.2, 5.4 Hz,
1H); 13C NMR (75 MHz, CDCl3) d 18.8, 18.9, 19.2, 24.9,
25.7, 28.3, 28.4, 34.1, 45.7, 46.1, 74.3, 74.8, 154.4, 176.2.
4.11.4. (1R,2S)-cis-1-Dimethylcarbamoyloxy-2-cyclo-
hexyl isobutyrate (8b) (entry 6, Table 3). HPLC (Daicel
Chiralpak AD-H, hexane–2-propanol¼40:1, flow rate¼
0.25 mL/min) tR¼57.8 ((1R,2S)-8b, major), 61.0 ((1S,2R)-
8b, minor) min. Anal. Calcd for C13H23NO4: C, 60.68; H,
9.01. Found: C, 60.59; H, 9.14. The absolute stereochemistry
of 8b was determined by analogy with that of 8a.
4.11.9. (L)-cis-1-(N-Pyrrolidine-10-carbonyloxy)-2-
cycloheptanol (11) (entry 5, Table 4).4c TLC (hexane–
EtOAc¼2:1) Rf ¼0.09; [a]2D0 ꢂ8.8 (c 1.0, CHCl3) for 93%
ee; HPLC (two linear Daicel Chiralcel OD-H columns, hex-
ane–2-propanol¼20:1, flow rate¼1.0 mL/min) tR¼37.0
(major) and 39.6 (minor) min; IR (film) 3500–3400 (br),
4.11.5. (1S,2R)-(L)-cis-N-(2-Hydroxycyclohexanoxycar-
bonyl)pyrrolidine (7c) (entry 2, Table 4). TLC (hexane–
EtOAc¼2:1) Rf¼0.17; [a]2D0 ꢂ2.7 (c 1.0, CHCl3) for 97%
ee; HPLC (Daicel Chiralpak AS-H, hexane–2-prop-
anol¼20:1, flow rate¼1.0 mL/min) tR¼24.7 ((1R,2S)-7c,
minor), 30.1 ((1S,2R)-7c, major) min; IR (film) 3500–3350
(br), 2938, 2871, 1680, 1429, 1360, 1181, 1129, 1109,
1
2933, 2871, 1678, 1429, 1180, 1129, 1106, 769 cmꢂ1; H
NMR (300 MHz, CDCl3) d 1.40–1.62 (m, 4H), 1.62–1.84
(m, 6H), 1.84–2.00 (m, 4H), 3.09 (s, 1H), 3.40 (t,
J¼6.6 Hz, 4H), 3.88–3.96 (m, 1H), 4.97 (dt, J¼2.4,
7.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 22.5, 22.8,
24.9, 25.7, 26.9, 28.9, 31.4, 73.5, 78.5, 155.4.
1
984, 768 cmꢂ1; H NMR (300 MHz, CDCl3) d 1.24–2.15
(m, 12H), 2.78 (s, 1H), 3.40 (t, J¼6.6 Hz, 4H), 3.83 (br,
1H), 4.92 (dt, J¼2.4, 6.6 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 21.3, 22.0, 24.9, 25.6, 28.2, 29.8, 45.8, 46.1,
70.1, 74.1, 155.1. Anal. Calcd for C11H19NO3: C, 61.95;
H, 8.98. Found: C, 61.91; H, 9.01. The absolute stereochem-
istry of 7c was determined by analogy with that of 7a.
4.11.10. (L)-cis-1-(N-Pyrrolidine-10-carbonyloxy)-2-
cycloheptyl isobutyrate (entry 5, Table 4).4c TLC (hex-
ane–EtOAc¼2:1) Rf ¼0.36; [a]2D0 ꢂ17.9 (c 1.0, CHCl3) for
92% ee; HPLC (two linear Daicel Chiralcel OD-H columns,
hexane–2-propanol¼20:1, flow rate¼1.0 mL/min) tR¼15.4
(minor) and 16.3 (major) min; IR (film) 2936, 2872, 1733,
4.11.6. (1R,2S)-(L)-cis-N-(2-Isobutyryloxycyclohexan-
oxycarbonyl)pyrrolidine (8c) (entry 2, Table 4). TLC
(hexane–EtOAc¼2:1) Rf¼0.27; [a]2D0 ꢂ24.4 (c 1.0, CHCl3)
for 90% ee; HPLC (Daicel Chiralpak AS-H, hexane–2-
propanol¼20:1, flow rate¼0.5 mL/min) tR¼13.5 ((1S,2R)-
8c, minor), 14.5 ((1R,2S)-8c, major) min; IR (CHCl3)
2876, 2943, 2875, 1728, 1694, 1425, 1372, 1196, 1128,
1703, 1419, 1195, 1157, 1100, 768 cmꢂ1
;
1H NMR
(300 MHz, CDCl3) d 1.17 (d, J¼7.0 Hz, 3H), 1.18 (d,
J¼7.0 Hz, 3H), 1.47–1.81 (m, 8H), 1.81–2.01 (m, 6H),
2.58 (septet, J¼7.0 Hz, 1H), 3.26–3.43 (m, 4H), 4.94–5.01
(m, 1H), 5.10–5.16 (m, 1H); 13C NMR (75 MHz, CDCl3)
d 18.9, 19.0, 22.5, 22.7, 24.9, 25.7, 26.6, 28.8, 29.1, 34.2,
45.6, 46.0, 74.5, 75.2, 154.4, 176.2.
1
1105, 756 cmꢂ1; H NMR (300 MHz, CDCl3) d 1.16 (d,
J¼3.3 Hz, 3H), 1.19 (d, J¼3.3 Hz, 3H), 1.36–1.52 (m,
2H), 1.52–1.75 (m, 4H), 1.75–1.94 (m, 6H), 2.56 (septet,
J¼6.9 Hz, 1H), 3.31 (t, J¼6.3 Hz, 2H), 3.38 (t, J¼6.0 Hz,
2H), 4.86–4.93 (m, 1H), 5.04–5.10 (m, 1H); 13C NMR
(75 MHz, CDCl3) d 18.9, 19.0, 21.2, 22.2, 24.9, 25.6, 27.8,
28.1, 34.2, 45.6, 46.0, 70.8, 71.7, 154.3, 176.1. Anal. Calcd
for C15H25NO4: C, 63.58; H, 8.89. Found: C, 63.46; H, 8.97.
The absolute stereochemistry of 8c was determined by anal-
ogy with that of 8a.
4.11.11. (2RS,3SR)-(L)-2-(N-Pyrrolidine-10-carbonyl-
oxy)-3-butanol (12) (entry 6, Table 4).17 TLC (hexane–
EtOAc¼2:1) Rf¼0.10; [a]2D0 ꢂ2.3 (c 1.0, CHCl3) for 82%
ee; HPLC (Daicel Chiralpak AD-H, hexane–2-propanol¼
20:1, flow rate¼1.0 mL/min) tR¼15.9 (major) and 20.8 (mi-
nor) min; IR (film) 3500–3350 (br), 2977, 2877, 1679, 1426,
1130, 1106, 769 cmꢂ1; 1H NMR (300 MHz, CDCl3) d 1.16
(d, J¼6.3 Hz, 3H), 1.22 (d, J¼6.6 Hz, 3H), 1.82–1.95 (m,
4H), 2.81 (s, 1H), 3.33–3.43 (m, 4H), 3.83–3.93 (m, 1H),
4.84 (dq, J¼2.7, 12.9 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 15.3, 17.2, 24.9, 25.6, 45.8, 46.2, 70.0, 75.1, 155.2.
4.11.7. (L)-cis-1-(N-Pyrrolidine-10-carbonyloxy)-2-
cyclopentanol (10) (entry 3, Table 4).4c TLC (hexane–
EtOAc¼2:1) Rf¼0.09; [a]2D0 ꢂ7.9 (c 1.0, CHCl3) for 90%
ee; HPLC (Daicel Chiralpak AD-H, hexane–2-prop-
anol¼20:1, flow rate¼1.0 mL/min) tR¼16.8 (major) and
24.8 (minor) min; IR (KBr) 3450–3350, 2980, 2951, 2874,
1661, 1443, 1360, 1173, 1115, 1037, 860, 769, 606,
4.11.12. (2RS,3SR)-(L)-2-(N-Pyrrolidine-10-carbonyl-
oxy)-3-butyl isobutyrate (entry 6, Table 4).17 TLC (hex-
ane–EtOAc¼2:1) Rf¼0.33; [a]2D0 ꢂ25.2 (c 1.0, CHCl3) for
93% ee; HPLC (Daicel Chiralpak AD-H, hexane–2-prop-
anol¼20:1, flow rate¼1.0 mL/min) tR¼7.1 (major) and 8.4
(minor) min; IR (film) 2978, 2877, 1734, 1705, 1416,
1
504 cmꢂ1; H NMR (300 MHz, CDCl3) d 1.49–1.61 (m,
1H), 1.61–1.77 (m, 1H), 1.77–2.02 (m, 8H), 2.54 (d,
J¼3.3 Hz, 1H), 3.34–3.43 (m, 4H), 4.13–4.21 (m, 1H),
4.93 (dt, J¼4.7, 6.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 19.4, 24.9, 25.7, 28.5, 30.5, 45.8, 46.2, 73.7, 77.4, 155.1.
1
1196, 1160, 1103, 768 cmꢂ1; H NMR (300 MHz, CDCl3)
d 1.16 (d, J¼7.2 Hz, 3H), 1.17 (d, J¼6.8 Hz, 3H), 1.21 (d,
J¼6.3 Hz, 3H), 1.24 (d, J¼6.8 Hz, 3H), 1.82–1.92 (m,

6200
Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
4H), 2.54 (septet, J¼7.0 Hz, 1H), 3.30 (t, J¼6.3 Hz, 2H),
3.38 (t, J¼6.3 Hz, 2H), 4.88 (dq, J¼4.1, 6.5 Hz, 1H), 3.38
(t, J¼6.3 Hz, 2H), 4.88 (dq, J¼4.1, 6.5 Hz, 1H), 5.03 (dq,
J¼4.1, 6.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 15.3,
15.5, 18.8, 19.0, 24.9, 25.6, 34.1, 45.6, 46.0, 71.3, 72.0,
154.3, 176.3.
49.7 (major) min; IR (KBr) 2973, 2875, 1731, 1628, 1459,
1
1438, 1200, 1162, 703 cmꢂ1; H NMR (300 MHz, CDCl3)
d 0.91 (d, J¼7.2 Hz, 3H), 1.07 (d, J¼7.2 Hz, 3H), 1.09 (d,
J¼7.2 Hz, 3H), 1.82–1.94 (m, 2H), 1.94–2.05 (m, 2H),
2.45 (septet, J¼6.9 Hz, 1H), 3.60 (dq, J¼3.9, 6.9 Hz, 1H),
3.45–3.56 (m, 3H), 3.68–3.78 (m, 1H), 5.77 (d,
J¼10.2 Hz, 1H), 7.26–7.39 (m, 5H); 13C NMR (75 MHz,
CDCl3) d 13.9, 18.5, 18.8, 24.4, 26.1, 33.9, 43.6, 45.8,
46.7, 78.4, 127.3 (2C), 128.1, 128.4 (2C), 138.9, 172.1,
174.9. Anal. Calcd for C18H25NO3: C, 71.26; H, 8.31.
Found: C, 71.18; H, 8.43.
4.11.13. (S)-(L)-N-(3-Hydroxy-3-phenylpropionyl)pyr-
rolidine (13) (entry 7, Table 4). TLC (hexane–EtOAc¼2:1)
Rf ¼0.22; [a]2D0 ꢂ51.5 (c 1.0, CHCl3) for 64% ee; HPLC
(Daicel Chiralpak AD-H, hexane–2-propanol¼20:1, flow
rate¼1.0 mL/min) tR¼30.2 (minor) and 32.1 (major) min;
IR (KBr) 3300–3200 (OH), 1609 (C]O), 1474, 1065,
4.11.17. (L)-cis-N-(20-Hydroxyindan-10-yl)pyrrolidine-
1-carboxamide (15) (entry 9, Table 5).4e,g TLC (EtOAc)
Rf ¼0.40; [a]2D0 ꢂ36.6 (c 1.0, CHCl3) for 67% ee; HPLC
(Daicel Chiralpak AD-H, hexane–2-propanol¼9:1, flow
rate¼1.0 mL/min) tR¼11.9 (major), 15.0 (minor) min; IR
(KBr) 3405, 3205, 1618, 1523, 1474, 1404, 1180, 1060,
1
707 cmꢂ1; H NMR (300 MHz, CDCl3) d 1.80–2.00 (m,
4H), 2.58 (dd, J¼8.7, 16.2 Hz, 1H), 2.65 (dd, J¼3.6,
16.2 Hz, 1H), 3.31 (t, J¼6.6 Hz, 2H), 3.48 (t, J¼6.3 Hz,
2H), 4.97 (d, J¼3.0 Hz, 1H), 5.16 (dt, J¼3.3, 8.7 Hz, 1H),
7.24–7.45 (m, 5H); 13C NMR (75 MHz, CDCl3) d 24.3,
25.8, 43.0, 45.5, 46.5, 70.3, 125.6 (2C), 127.4, 128.4 (2C),
143.1, 170.7. Anal. Calcd for C13H17NO2: C, 71.21; H,
7.81. Found: C, 71.19; H, 7.99. The absolute stereochemistry
of 13 was determined by comparison with authentic (S)-13
derived from ethyl (S)-3-phenylpropionate, which was com-
mercially available.
1
744 cmꢂ1; H NMR (300 MHz, CDCl3) d 1.90–1.97 (m,
4H), 1.93 (s, 1H), 2.96 (dd, J¼3.6, 16.5 Hz, 1H), 3.17 (dd,
J¼5.6, 16.5 Hz, 1H), 3.34–3.44 (m, 4H), 4.61–4.68 (m,
1H), 4.71 (d, J¼7.5 Hz, 1H), 5.29 (dd, J¼5.3, 7.4 Hz, 1H),
7.19–7.36 (m, 4H); 13C NMR (75 MHz, CDCl3) d 25.5
(2C), 39.1, 45.7 (2C), 58.8, 73.9, 124.7, 125.3, 127.1,
128.3, 140.4, 141.3, 157.2.
4.11.14. (R)-(D)-N-(3-Isobutyryloxy-3-phenylpropio-
nyl)pyrrolidine. TLC (hexane–EtOAc¼1:2) Rf ¼0.35;
[a]2D0 29.5 (c 1.0, CHCl3); HPLC (Daicel Chiralpak AD-H,
hexane–2-propanol¼20:1, flow rate¼1.0 mL/min) tR¼36.5
(major) and 45.0 (minor) min; 1H NMR (300 MHz,
CDCl3) d 1.15 (t, J¼7.1 Hz, 6H), 1.76–1.95 (m, 4H), 2.56
(septet, J¼7.1 Hz, 1H), 2.65 (dd, J¼5.4, 15.0 Hz, 1H),
2.94 (dd, J¼8.3, 15.0 Hz, 1H), 3.22–3.31 (m, 1H), 3.40–
3.51 (m, 3H), 6.21 (dd, J¼5.4, 8.3 Hz, 1H), 7.24–7.41 (m,
5H); 13C NMR (75 MHz, CDCl3) d 18.8 (2C), 24.3, 26.0,
33.9, 42.0, 45.6, 46.7, 72.6, 126.2 (2C), 127.9, 128.5 (2C),
140.5, 167.6, 175.6. Anal. Calcd for C17H23NO3: C, 70.56;
H, 8.01. Found: C, 70.67; H, 7.93. The absolute stereochem-
istry of this compound was determined by comparison with
authentic sample derived from ethyl (S)-3-phenylpropio-
nate, which was commercially available.
4.11.18. (D)-cis-N-(20-Isobutyryloxyindan-10-yl)pyrroli-
dine-1-carboxamide (entry 9, Table 5).4e,g TLC (hexane–
EtOAc¼1:2) Rf ¼0.34; [a]2D0 70.0 (c 1.0, CHCl3) for 93%
ee; HPLC (Daicel Chiralpak AD-H, hexane–2-prop-
anol¼9:1, flow rate¼1.0 mL/min) tR¼16.7 (major), 24.6
(minor) min; IR (KBr) 3550–3300 (br), 1729, 1642, 1622,
1
1524, 1403, 1189, 1151, 1037 cmꢂ1; H NMR (300 MHz,
CDCl3) d 1.03 (d, J¼6.0 Hz, 3H), 1.05 (d, J¼6.0 Hz, 3H),
1.82–1.90 (m, 4H), 2.40 (septet, J¼7.0 Hz, 1H), 2.89 (d,
J¼17.4 Hz, 1H), 3.16 (dd, J¼5.1, 17.4 Hz, 1H), 3.23–3.38
(m, 4H), 4.62 (d, J¼9.3 Hz, 1H), 5.48 (dt, J¼0.9, 5.6 Hz,
1H), 5.58 (dd, J¼5.6, 9.2 Hz, 1H), 7.13–7.21 (m, 3H),
7.25–7.30 (m, 1H); 13C NMR (75 MHz, CDCl3) d 18.7,
19.1, 23.5 (2C), 34.0, 37.7, 45.6 (2C), 56.7, 76.0, 123.9,
124.9, 127.1, 127.9, 139.4, 141.9, 156.2, 176.2.
4.11.15. (2SR,3RS)-(L)-N-(3-Hydroxy-2-methyl-3-phe-
nylpropionyl)pyrrolidine (14) (entry 1, Table 5). TLC
(hexane–EtOAc¼1:2) Rf¼0.35; [a]2D0 ꢂ80.1 (c 1.0, CHCl3)
for 80% ee; HPLC (Daicel Chiralpak AD-H, hexane–2-
propanol¼20:1, flow rate¼1.0 mL/min) tR¼26.6 (major)
and 28.4 (minor) min; IR (KBr) 3400–3300 (OH), 2976,
4.11.19. (2R,3R)-(L)-2-(N-Pyrrolidine-10-carboxamino)-
3-hydroxybutyric acid methyl ester (16) (entry 10, Table
4). TLC (hexane–EtOAc¼1:5) Rf ¼0.17; [a]2D0 ꢂ32.0 (c 1.0,
CHCl3) for 51% ee; HPLC (Daicel Chiralpak AS-H,
hexane–2-propanol¼5:1, flow rate¼0.5 mL/min) tR¼23.5
(major), 27.7 (minor) min; IR (KBr) 3400–3300 (br), 2987,
2956, 2879, 1751, 1616, 1526, 1433, 1191, 1163 cmꢂ1; 1H
NMR (300 MHz, CDCl3) d 1.11 (d, J¼6.3 Hz, 3H), 1.91–
1.96 (m, 4H), 3.36–3.42 (m, 4H), 3.79 (s, 3H), 4.17–4.27
(m, 1H), 4.40 (d, J¼5.4 Hz, 1H), 4.68 (dd, J¼3.3, 6.0 Hz,
1H), 5.25 (d, J¼5.7 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 18.0, 25.5 (2C), 45.7 (2C), 52.6, 59.1, 69.1, 157.0, 171.6.
Anal. Calcd for C10H18N2O4: C, 52.16; H, 7.88. Found: C,
52.11; H, 7.90. The absolute stereochemistry of 16 was deter-
mined by comparison with authentic (S)-16 derived from
(2S,3S)-L-allothreonine, which was commercially available.
1
2872, 1613, 1469, 1447, 1047, 756, 702 cmꢂ1; H NMR
(300 MHz, CDCl3) d 1.25 (d, J¼7.2 Hz, 3H), 1.65–1.87
(m, 4H), 2.86 (dq, J¼7.2, 2.1 Hz, 1H), 2.96–3.05 (m, 1H),
3.23–3.32 (m, 1H), 3.34–3.41 (m, 2H), 4.64 (d, J¼7.2 Hz,
1H), 4.77 (dd, J¼5.1, 6.9 Hz, 1H), 7.21–7.37 (m, 5H); 13C
NMR (75 MHz, CDCl3) d 15.3, 24.1, 25.8, 44.8, 45.4,
46.5, 76.6, 125.9 (2C), 127.4, 128.2 (2C), 143.3, 174.1.
Anal. Calcd for C14H19NO2: C, 72.07; H, 8.21. Found: C,
72.21; H, 8.13.
4.11.16. (D)-N-(3-Isobutyryloxy-2-methyl-3-phenylpro-
pionyl)pyrrolidine (19) (entry 1, Table 5). TLC (hexane–
EtOAc¼1:1) Rf ¼0.19; [a]2D0 55.8 (c 1.0, CHCl3) for 82%
ee; HPLC (Daicel Chiralpak AD-H, hexane–2-prop-
anol¼20:1, flow rate¼1.0 mL/min) tR¼27.4 (minor) and
4.11.20. (2S,3S)-(D)-2-(N-Pyrrolidine-1-carboxamino)-
3-isobutyryloxybutyric acid methyl ester (entry 10, Table
4). TLC (hexane–EtOAc¼1:2) Rf ¼0.34; [a]2D0 1.1 (c 1.0,
CHCl3) for 80% ee; HPLC (Daicel Chiralpak AS-H,

Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
6201
hexane–2-propanol¼5:1, flow rate¼0.5 mL/min) tR¼12.6
(major), 15.6 (minor) min; IR (KBr) 3354, 3290, 2979,
2944, 2875, 1739, 1639, 1535, 1416, 1197, 1161 cmꢂ1; 1H
NMR (300 MHz, CDCl3) d 1.14 (d, J¼4.8 Hz, 3H), 1.32
(d, J¼4.8 Hz, 3H), 1.36 (d, J¼6.6 Hz, 3H), 1.89–1.94 (m,
4H), 2.53 (septet, J¼7.0 Hz, 1H), 3.33–3.39 (m, 4H), 3.77
(s, 3H), 4.69 (dd, J¼3.6, 8.1 Hz, 1H), 5.13 (dq, J¼3.3,
12.9 Hz, 1H), 5.21 (d, J¼8.1 Hz, 1H), 4.69 (dd, J¼3.6,
8.1 Hz, 1H), 5.13 (dq, J¼3.3, 12.9 Hz, 1H), 5.21 (d,
J¼8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 17.2, 18.7,
18.9, 25.5 (2C), 34.0, 45.5 (2C), 52.3, 57.3, 71.4, 155.7,
171.0, 176.9. Anal. Calcd for C14H24N2O5: C, 55.98; H,
8.05. Found: C, 55.91; H, 8.08. The absolute stereochemistry
of this compound was determined by comparison with au-
thentic sample derived from (2S,3S)-L-allothreonine, which
was commercially available.
4.11.24. (L)-2-Phenyl-2-(pyrrolidine-1-carboxamino)-
ethyl isobutyrate (entry 12, Table 4). [a]2D0 ꢂ1.9 (c 3.7,
CHCl3) for 74% ee; HPLC (Daicel Chiralpak AS-H,
hexane–2-propanol¼5:1, flow rate¼1.0 mL/min) tR¼7.4
(minor), 11.8 (major) min; IR (KBr) 3441, 3325, 2974,
2874, 1731, 1627, 1544, 1411, 1191, 1153, 703, 702 cmꢂ1
;
1H NMR (300 MHz, CDCl3) d 1.11 (d, J¼6.91 Hz, 6H)
1.85–1.96 (m, 4H), 2.54 (septet, J¼7.0 Hz, 1H), 3.26–3.42
(m, 4H), 4.22 (dd, J¼4.8, 11.4 Hz, 1H), 4.51 (dd, J¼7.5,
11.4 Hz, 1H), 4.97 (br, 1H), 5.22 (dt, J¼4.8, 7.5 Hz, 1H),
7.23–7.36 (m, 5H); 13C NMR (75 MHz, CDCl3) d 18.9
(2C), 25.5 (2C), 33.9, 45.4 (2C), 53.8, 66.4, 126.6 (2C),
127.5, 128.5 (2C), 139.6, 155.8, 177.7.
4.12. Procedure for the preparation of polystyrene-
bound catalyst 3
4.11.21. (S)-(L)-3-Methyl-2-(N-pyrrolidine-1-carbox-
amino)-1-butanol (17) (entry 11, Table 4). TLC (EtOAc)
Rf ¼0.14; [a]2D0 ꢂ37.2 (c 1.0, CHCl3) for 88% ee; HPLC
(Daicel Chiralpak AS-H, hexane–2-propanol¼5:1, flow
rate¼0.5 mL/min) tR¼11.1 (major), 14.5 (minor) min; IR
(KBr) 3364, 3292, 2969, 2869, 1608, 1525, 1408, 1335,
(4-Methoxyphenyl)diisopropylsilylpropyl polystyrene (20,
1.40 mmol of Si/g, 50–100 mesh; the polymer matrix is
copolystyrene–1% divinylbenzene)12 that had been dried
under vacuum for 12 h was weighted (212 mg, 0.297 mmol)
into a flask and swollen in CH2Cl2 (2.1 mL, 10 mL of sol-
vent per gram of resin) under a N2 atmosphere for 30 min.
The solvent was then drained under positive N2 pressure
and a 4% trifluoromethanesulfonic acid–CH2Cl2 solution
(6 equiv of TfOH relative to Si) was added by syringe. The
resin turned bright red/orange upon acid treatment and
then gently agitated for 30 min while still under the N2
atmosphere. Once activation was complete, the resin was
washed twice with CH2Cl2 to remove excess acid. Treatment
of silyl triflate functionalized resin with 2,6-lutidine
(280 mL, 2.40 mmol, 8 equiv relative to Si) for 15 min
followed by the addition of an azeotropically dried solution
of 21 (253 mg, 0.600 mmol) in CH2Cl2 (1.2 mL) resulted
in a colorless resin. The beads were then gently agitated
for an additional 10 h under a N2 atmosphere. The
beads were drained, exposed to room temperature, and sub-
jected to the following wash protocol: CH2Cl2 (2ꢁ3 mLꢁ
45 min), THF (2ꢁ3 mLꢁ30 min), THF–i-Pr2EtN (3:1,
2ꢁ3 mLꢁ30 min), THF–IPA (3:1, 2ꢁ3 mLꢁ30 min),
THF–H2O (3:1, 2ꢁ3 mLꢁ30 min), and THF–IPA (3:1,
2ꢁ3 mLꢁ30 min), DMF (2ꢁ3 mLꢁ30 min), THF (2ꢁ
3 mLꢁ30 min). The resin was air-dried for 3 h and then
placed under high vacuum for 24 h to remove trace solvent
and H2O to give 3. The mass of 3 was 278 mg
(0.229 mmol, 0.824 mmol of imidazole moiety per gram),
indicating an apparent loading efficiency of 77% based on
weight gain.
1086 cmꢂ1
;
1H NMR (300 MHz, CDCl3) d 0.95 (d,
J¼5.1 Hz, 3H), 0.97 (d, J¼5.1 Hz, 3H), 1.84–1.99 (m,
5H), 3.31–3.39 (m, 4H), 3.55–3.68 (m, 2H), 3.68–3.78 (m,
1H), 3.98 (t, J¼4.8 Hz, 1H), 4.39 (d, J¼6.0 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d 18.8, 19.6, 25.5 (2C), 29.4, 45.6
(2C), 58.2, 65.4, 157.9. Anal. Calcd for C10H20N2O2: C,
59.97; H, 10.07. Found: C, 59.89; H, 10.12. The absolute
stereochemistry of 17 was determined by comparison with
authentic (S)-16 derived from (S)-L-valine, which was com-
mercially available.
4.11.22. (R)-(D)-Isobutyryloxy-3-methyl-2-(N-pyrroli-
dine-1-carboxamino)butane (entry 11, Table 4). TLC
(hexane–EtOAc¼1:5) Rf¼0.33; [a]2D0 30.6 (c 1.0, CHCl3) for
86% ee; HPLC (Daicel Chiralpak AS-H, hexane–2-prop-
anol¼5:1, flow rate¼0.5 mL/min) tR¼9.0 (minor), 13.0 (ma-
jor) min; IR (KBr) 3313, 2969, 2872, 1731, 1625, 1533,
1
1469, 1405, 1195, 1161, 1081 cmꢂ1; H NMR (300 MHz,
CDCl3) d 0.96 (d, J¼6.6 Hz, 6H), 1.14 (d, J¼2.1 Hz, 3H),
1.17 (d, J¼2.1 Hz, 3H), 1.84 (septet, J¼6.7 Hz, 1H), 1.87–
1.94 (m, 4H), 2.56 (septet, J¼7.0 Hz, 1H), 3.32 (t,
J¼6.6 Hz, 4H), 3.90–4.06 (m, 2H), 4.23–4.35 (m, 2H); 13C
NMR (75 MHz, CDCl3) d 18.6, 18.9, 19.2, 25.5 (2C), 29.9,
34.0, 45.4 (2C), 54.3, 64.7, 156.4, 177.5. Anal. Calcd for
C14H26N2O3: C, 62.19; H, 9.69. Found: C, 62.22; H, 9.75.
The absolute stereochemistry of this compound was deter-
mined by comparison with authentic sample derived from
(S)-L-valine, which was commercially available.
4.13. Procedure for the kinetic resolution of ( )-7a
induced by reusable catalyst 3
4.11.23. (L)-N-(2-Hydroxy-1-phenylethyl)pyrrolidine-1-
carboxamide (18) (entry 12, Table 4). [a]2D0 ꢂ3.9 (c 2.4,
CHCl3) for 83% ee; HPLC (Daicel Chiralpak AS-H, hex-
ane–2-propanol¼5:1, flow rate¼1.0 mL/min) tR¼7.4 (ma-
jor), 11.4 (minor) min; IR (KBr) 3350, 2971, 2875, 2360,
To a suspension of (ꢀ)-7a (53.3 mg, 0.25 mmol) and 3
(15.2 mg, 0.0125 mmol, 0.824 mmol/g) in CCl4 (2.5 mL)
were added i-Pr2NEt (21.8 mL, 0.125 mmol) and isobutyric
anhydride (20.7 mL, 0.125 mmol). After being shaken at
0 ꢃC for 7 h, 3 was recovered by filtration and washed
with toluene (2ꢁ3 mL). Thus, 3 was reused more than five
times without any loss of activity or selectivity. The com-
bined filtrate was concentrated under reduced pressure and
the residue was analyzed without purification. The ee values
for the recovered alcohol 7a and the acylated product 8a
were determined by HPLC analysis: (1S,2R)-7a (major
1
1616, 1545, 1522, 1412, 1346, 1075, 755, 702 cmꢂ1; H
NMR (300 MHz, CDCl3) d 1.86–1.98 (m, 4H), 3.24–3.44
(m, 4H), 3.84 (d, J¼5.4 Hz, 2H), 4.08 (br, 1H), 4.88 (d,
J¼6.0 Hz, 1H), 4.96 (q, J¼5.5 Hz, 2H), 7.23–7.41 (m,
5H); 13C NMR (75 MHz, CDCl3) d 25.5 (2C), 45.7 (2C),
57.3, 67.2, 126.6, 127.7, 128.8, 140.1, 157.3.

6202
Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
enantiomer), 82–86% ee and (1R,2S)-8a (major enantio-
mer), 62–65% ee. The conversion from 7a to 8a was deter-
mined to be 42–44% by the following equation,
conversion (%)¼[ee (recovered alcohol)]/[ee (recovered
alcohol)+ee (acylated product)].9
Acknowledgements
Financial support for this project was provided by JSPS,
KAKENHI (15205021), the 21st Century COE Program
‘Nature-Guided Materials Processing’ of MEXT, and the
Toray Science and Technology Grant.
4.14. Computational methods
References and notes
Theoretical calculations were performed using the Gaussian
98 program.10 Gradient-corrected density functional theory
(DFT) with Becke’s three-parameter exchange with the
Lee, Yang, and Parr correlation functional (B3LYP)11 were
carried out using the 6-311++G(d,p) basis set. After satisfac-
tory optimization, the vibrational spectrum of each species
was calculated.
1. Theil, F. Chem. Rev. 1995, 95, 2203.
2. For a recent review, see: Ghanem, A.; Aboul-Enein, H. Y.
Chirality 2005, 17, 1.
3. Vedejs, E.; Chen, X. J. Am. Chem. Soc. 1996, 118, 1809.
4. (a) Fu, G. C. Acc. Chem. Res. 2004, 37, 542, and references
therein; (b) Ruble, J. C.; Latham, H. A.; Fu, G. C. J. Am.
Chem. Soc. 1997, 119, 1492; (c) Kawabata, T.; Nagato, M.;
Takasu, K.; Fuji, K. J. Am. Chem. Soc. 1997, 119, 3169; (d)
Spivey, A. C.; Fekner, T.; Spay, S. E. J. Org. Chem. 2000, 65,
3154; (e) Kawabata, T.; Yamamoto, K.; Homose, Y.; Yoshida,
H.; Nagaoka, Y.; Fuji, K. Chem. Commun. 2001, 2700; (f)
Kawabata, T.; Stragies, R.; Fukaya, T.; Fuji, K. Chirality
2003, 15, 71; (g) Priem, G.; Pelotier, B.; Macdonald, S. J. F.;
Anson, M. S.; Campbell, I. B. J. Org. Chem. 2003, 68, 3844;
(h) Pelotier, B.; Priem, G.; Campbell, I. B.; Macdonald,
S. J. F.; Anson, M. S. Synlett 2003, 679; (i) Naraku, G.;
Shimomoto, N.; Hanamoto, T.; Inanaga, J. Enantiomer
2000, 5, 135.
4.15. X-ray diffraction analysis of 1c
X-ray crystallographic analysis was performed with a Bruker
SMART APEX diffractometer (graphite monochromator,
˚
Mo Ka radiation, l¼0.71073 A) and the structure was
solved by direct methods and expanded using Fourier tech-
niques (Sir97 and SHELXL18).
Recrystallization of 1c was carried out in the solution of
chloroform–hexane at room temperature. Mp 178 ꢃC. Crys-
tallographic data have been deposited with Cambridge
Crystallographic Data Centre: Deposition number CCDC
253176. Copies of the data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033;
or deposit@ccdc.cam.ac.uk) (Table 7).
5. (a) Miller, S. J. Acc. Chem. Res. 2004, 37, 601; (b) Vasbinder,
M. M.; Jarvo, E. R.; Miller, S. J. Angew. Chem., Int. Ed. 2001,
40, 2824; (c) Miller, S. J.; Copeland, G. T.; Papaioannou, N.;
Horstmann, T. E.; Ruel, E. M. J. Am. Chem. Soc. 1998, 120,
1629.
6. (a) Birman, V. B.; Uffman, E. W.; Jiang, H.; Li, X.; Kilbane,
C. J. J. Am. Chem. Soc. 2004, 126, 12226; (b) Birman, V. B.;
Jiang, H. Org. Lett. 2005, 7, 3445; (c) Birman, V. B.;
Li, X. Org. Lett. 2006, 8, 1351; (d) Birman, V. B.; Jiang,
H.; Li, X.; Guo, L.; Uffman, E. W. J. Am. Chem. Soc. 2006,
128, 6536; (e) Birman, V. B.; Guo, L. Org. Lett. 2006, 8,
4859.
7. (a) Part of this work has been published as a preliminary
communication: Ishihara, K.; Kosugi, Y.; Akakura, M. J. Am.
Chem. Soc. 2004, 126, 12212; (b) For an account, see:
Ishihara, K.; Sakakura, A.; Hatano, M. Synlett, in press.
8. Gonzalez, F. B.; Baz, J. P.; Espina, M. I. R. Tetrahedron Lett.
1989, 30, 2145.
9. Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, 249.
10. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.;
Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari,
K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.;
Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.;
Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98; Gaussian:
Pittsburgh, PA, 1998.
Table 7. Crystallographic data and structure refinement for 1c
Compound
Empirical formula
Formula weight
T
l
Crystal system
1c
C38H53N3O3SSi
659.98
173(2) K
0.71073 A
Orthorhombic
˚
Space group
A
B
C
a
b
g
V
Z
Dcalcd
P212121
10.1626(9) A
˚
˚
21.9774(19) A
˚
34.178(3) A
90.00ꢃ
90.00ꢃ
90.00ꢃ
3
˚
7633.6(11) A
8
1.149 g/cm3
0.154 mmꢂ1
2848
Absorption coefficient
F(000)
Crystal size
0.30ꢁ0.20ꢁ0.20 mm3
1.51–29.18ꢃ
58,323
Theta range for data collection
Reflections collected
Independent reflections
Rint
20,367
0.0378
Refinement based on F2
No. of data
20,367
849
0
No. of parameters
No. of restraints
GOF
R(F) for I>2s(I)
wR2(F2) for all data
Drmin
1.079
0.0627
0.1716
ꢂ0.340 e ꢂA3
˚
0.918 e A
ꢂ3
˚
Drmax

Y. Kosugi et al. / Tetrahedron 63 (2007) 6191–6203
6203
11. (a) Becke, A. D. J. Chem. Phys. 1993, 96, 5648; (b) Stevens,
P. J.; Devlin, J. F.; Chablowski, C. F.; Frisch, M. J. J. Phys.
Chem. 1994, 98, 11623.
14. Saednya, A.; Hart, H. Synthesis 1996, 1455.
15. Garr, G. E.; Chambers, R. D.; Holmes, T. F. J. Organomet.
Chem. 1987, 325, 13.
12. Compound 20 was purchased from NovabiochemÒ. (a)
Woodlard, F. X.; Paetsch, J.; Ellman, J. A. J. Org. Chem.
1997, 62, 6102; (b) Tallarico, J. A.; Depew, K. M.; Pelish,
H. E.; Westwood, N. J.; Lindsley, C. W.; Shair, M. D.;
Schreiber, S. L.; Foley, M. A. J. Comb. Chem. 2001, 3, 312.
16. Matsumoto, K.; Sato, Y.; Shimojo, M.; Hatanaka, M.
Tetrahedron: Asymmetry 2000, 11, 1965.
17. Tomio, K.; Kawabata, T.; Nagato, M. Jpn. Kokai Tokkyo Koho
1998, JP 10077283, A219980324Heisei, p 9.
18. Sheldrick, G. M. SHELXL-97, Program for Crystal Structure
€
€
Refinement; University of Gottingen: Gottingen, Germany,
1997.
€
13. Lunig, U.; Baumgartner, H.; Manthey, C.; Meynhardt, B.
J. Org. Chem. 1996, 61, 7922.