Organocatalytic kinetic resolution of racemic primary alcohols using a chiral 1,2-diamine derived from (S)-proline

Article abstract of DOI:10.1016/j.tetasy.2005.01.034

A highly efficient and good enantioselective organocatalytic asymmetric acylation of racemic primary alcohols with acyl chlorides has been achieved catalyzed by a chiral 1,2-diamine derived from (S)-proline.

Full text of DOI:10.1016/j.tetasy.2005.01.034

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1157–1165
Organocatalytic kinetic resolution of racemic primary
alcohols using a chiral 1,2-diamine derived from (S)-proline
Dai Terakado, Hitomi Koutaka and Takeshi Oriyama*
Faculty of Science, Ibaraki University, Mito, Ibaraki 310-8512, Japan
Received 26 November 2004; revised 22 January 2005; accepted 24 January 2005
Abstract—A highly efficient and good enantioselective organocatalytic asymmetric acylation of racemic primary alcohols with acyl
chlorides has been achieved catalyzed by a chiral 1,2-diamine derived from (S)-proline.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
acylation of alcohols.9 As part of these investigations,
we presented a highly efficient and enantioselective ki-
netic resolution of racemic secondary alcohols catalyzed
by a chiral 1,2-diamine derived from (S)-proline
(Scheme 1).10 This reaction has advantages, such as
high efficiency and excellent enantioselectivity, extensive
substrate generality, and very low catalyst loading. On
the other hand, the kinetic resolution of racemic pri-
mary alcohols is supposed to be very difficult because
the reactive site and the asymmetric carbon center
are far apart. In fact, the enantioselectivity obtained
by an enzymatic method is hardly satisfactory
(E = ꢀ50).11 Therefore, we extended the kinetic resolu-
tion of racemic primary alcohols using a chiral
organocatalyst.
The kinetic resolution of racemic alcohols via asymmet-
ric acylation has been widely used to construct various
useful chiral building blocks in the synthesis of complex
natural products.1 Most methods reported so far have
employed enzymes, such as a lipase or esterase.2 The
asymmetric acylation of alcohols using molecular cata-
lysts has emerged as a viable alternative to the well-
established enzyme-catalyzed acylation. For example,
Vedejs et al. have reported the kinetic resolution of
racemic secondary alcohols using a highly modified chi-
ral phosphine catalyst.3 Fu et al. achieved the asymmet-
ric acylation of racemic secondary aryl carbinols using
acetic anhydride catalyzed by chiral dimethylaminopyri-
dine derivatives having a ferrocene unit.4 Miller et al.
have reported the asymmetric acylation of racemic sec-
ondary hydroxy amides catalyzed by oligopeptide,5
while Spivey et al. reported the kinetic resolution of
racemic secondary aryl carbinols catalyzed by atropiso-
meric dimethylaminopyridine derivatives, which contain
a chiral axis meta-position to the pyridyl nitrogen.6 Oth-
ers have also reported the kinetic resolution of racemic
secondary alcohol using chiral dimethylaminopyridine
derivatives7 or organocopper reagent8 and so on. Re-
cent disclosures from our laboratories have demon-
strated the synthetic potential of a simple 1,2-diamine
as an efficient chiral organocatalyst for asymmetric
Herein, we report a kinetic resolution of various racemic
primary alcohols catalyzed by a chiral 1,2-diamine
derived from (S)-proline.
2. Results and discussion
2.1. Kinetic resolution of various glycerol derivatives
Initially, we investigated the kinetic resolution of gly-
cerol derivatives having two protected hydroxy functions
as a model substrate of racemic primary alcohols due to
the pioneering work of desymmetrization of glycerol
derivatives using chiral 1,2-diamine was reported by
Mukaiyama and co-workers.12 The treatment of 2,3-O-
(isopropylidene)glycerol with benzoyl chloride (0.75 equiv)
*
Corresponding author. Tel.: +81 029 228 8368; fax: +81 029 228
8406; e-mail: tor@mx.ibaraki.ac.jp
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.01.034

1158
D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
0.3 mol%
N
N
Me
OH
Ph
OBz
Ph
OH
+
+
BzCl
°
Et3N / MS 4A
CH2Cl2 / -78 °C / 3 h
Ph
( )
49%, 96% ee
48%, 95% ee
s = 160
Scheme 1. Non-enzymatic kinetic resolution of a racemic secondary alcohol catalyzed by a chiral 1,2-diamine.
under the influence of (S)-1-methyl-2-[(benzylmethyl-
amino)methyl]pyrrolidine (0.3 mol %) combined with
diisopropylethylamine (0.5 equiv) at À78 °C in dichloro-
methane for 3 h gave the corresponding benzoate in 44%
yield with 56% ee and the unreacted alcohol in 33% iso-
lated yield with 69% ee (Table 1, run 1). The absolute
configuration of 4-benzoyloxymethyl-2,2-dimethyl-1,3-
dioxolane was assigned to be (R)- by comparison of
optical rotation with reported value.13 The enantio-
meric excess was determined by HPLC analysis with a
chiral column. The kinetic resolution of the glycerol
derivative protected by di-n-propyl acetal gave s = 7.0
selectivity (run 2). Substrates with n-Bu or cyclohexylid-
ene substituents showed moderate selectivity (runs 3 and
4). When sterically hindered 1,3-dioxolane having two
isopropyl groups was used, comparatively high s value
(s = 7.3) was acquired (run 5). 1,3-Dioxolanes having
cyclohexyl and phenyl groups gave also comparable re-
sults from the standpoint of selectivity (runs 6 and 8).
The enantioselectivity was decreased by the use of ben-
zyl groups (run 7).
2.2. Kinetic resolution of glycerol derivatives with various
acylating agent
Next, we tested the acylating agent (Table 2). When the
substituent on the aromatic ring of benzoyl chloride was
explored (ortho-Me, meta-Me, para-Me), it was found
that the para-substituted benzoate showed a higher
selectivity than the ortho- and meta-substituted ones
(runs 2–4). Among the para-substituents tested, such
as the electron-donating and electron-withdrawing
groups (runs 4–7), the para-Me group gave an s = 9.8
selectivity (run 4). a-Naphthoyl chloride gave a low
chemical yield and selectivity because of its insolubility
with methylene chloride at À78 °C (run 8). When mixed
Table 1. Kinetic resolution of various glycerol derivatives
0.3 mol%
Me
N
0.75 eq.
N
R
R
R
Bn
R
Me
R
R
O
BzCl
+
O
O
+
°
O
OH
O
O
OBz
OH
i-Pr2NEt (0.5 eq.) / MS 4A
CH2Cl2 / -78 °C / 3 h
( )-1a-h
2a-h
3a-h
Eeb/%
Run
R
Ester 2a–h
Alcohol 3a–h
sc
Yield/%
Eea/%
Yield/%
1
Me (1a)
n-Pr (1b)
n-Bu (1c)
44
49
52
49
52
54
53
51
56
60
54
53
59
51
23
54
33
37
41
41
39
43
47
45
69
64
71
65
75
82
29
62
5.4
7.0
5.9
5.3
7.3
5.5
2.0
5.8
2d,e
3
4d
–(CH2)5– (1d)
i-Pr (1e)
5
6
cyclo-Hex (1f)
Bn (1g)
Ph (1h)
7
8
a Determined by HPLC analysis with a chiral column.
b Determined by HPLC analysis with a chiral column after converted to the corresponding benzoate.
c s Value was calculated by the equation. See Ref. 19. In this place, conversion of products adopts chemical yield of acylated esters as an expedient.
d 0.5 mol % of chiral diamine was used.
e When 0.5 mol % of (S)-1-methyl-2-[(dihydroisoindol-2-yl)methyl]pyrrolidine was used, 51%, 6% ee of ester and 46%, 8% ee of unreacted alcohol
were obtained, respectively.

D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
1159
Table 2. The effect of acyl chloride
0.3 mol%
Me
i-Pr
O
i-Pr
O
N
i-Pr
i-Pr
O
N
i-Pr
0.75 eq.
ArCOCl
i-Pr
Bn
+
O
OCOAr
+
Me
O
OH
O
OH
i-Pr2NEt (0.5 eq.) / MS 4Å
4a-i
CH2Cl2 / -78oC / 3h
3e
( )-1e
Run
ArCOCl
PhCOCl
Ester 4a–i
Alcohol 3e
s
Yield/%
Eea/%
Yield/%
Eeb/%
1
52 (4a)
21 (4b)
54 (4c)
48 (4d)
55 (4e)
39 (4f)
53 (4g)
20 (4h)
38 (4h)
47 (4h)
13 (4i)
59
61
51
68
57
70
51
67
81
77
78
39
44
37
43
36
32
41
57
50
46
77
75
15
79
81
84
44
76
23
48
68
10
7.3
2
2-MeC6H4COCl
3-MeC6H4COCl
4-MeC6H4COCl
4.8
5.5
9.8
7.4
8.7
5.4
6.0
3
4
5
4-t-BuC6H4COCl
4-MeOC6H4COCl
4-CIC6H4COCl
6
7
8
a-Naphthoyl chloride
a-Naphthoyl chloride
a-Naphthoyl chloride
b-Naphthoyl chloride
9c
10c,d
11c
16
16
9.1
a Determined by HPLC analysis with a chiral column.
b Determined by HPLC analysis with a chiral column after converted to the corresponding benzoate.
c CH2Cl2–DMF (9:1) was used as a solvent.
d The reaction was performed in 30 mmol scale.
0.3 mol%
Me
i-Pr
O
0.8 eq.
i-Pr
O
N
i-Pr
O
N
Me
i-Pr
i-Pr
i-Pr
Bn
O
OH
+
O
+
OCOAr
ArCOCl
O
OH
i-Pr NEt (0.7 eq.) / MS 4 °
CH2Cl2 - DMF (9 : 1)
A
2
( )
Ar = 4-MeC6H4
62%, 48% ee
29%, 97% ee
-78 °C / 3 h
Scheme 2. Kinetic resolution of glycerol derivatives.
solvents [CH2Cl2–DMF (9:1)] were used, s = 16
selectivity was obtained (run 9). In addition, we demon-
strated that the reaction proceeds efficiently on a
30 mmol scale (run 10).
rane, aziridine, tetrahydrofuran, and tetrahydropyran
showed moderate selectivities (runs 2–6). 2-Phenylcyclo-
propane-1-methanol, which does not contain a hetero-
atom except for a hydroxyl group in the molecule, was
ineffective from the standpoint of enantioselectivity
(run 7).
We succeeded in increasing the enantiomeric excess of the
unreacted alcohol by up to 97% ee by progressing acyla-
tion over 60% using 0.8 equiv of 4-methylbenzoyl chlo-
ride and 0.7 equiv of diisopropylethylamine (Scheme 2).
3. Conclusion
2.3. Kinetic resolution of various racemic primary alcohols
In summary, we have demonstrated the kinetic resolu-
tion of racemic primary alcohols catalyzed by a chiral
1,2-diamine. To the best of our knowledge, this is the first
example of a non-enzymatic catalytic kinetic resolution
of racemic primary alcohols attaining high selectivities.
The reactions of various racemic primary alcohols, hav-
ing heterocycles and a cyclopropane ring, were examined.
The results are summarized in Scheme 3 and Table 3. The
kinetic resolution of glycidol was performed by succes-
sive acylation and silylation in order to isolate unreacted
alcohol. Consequently, the corresponding benzoate and
silyl ether were directly obtained in 36% chemical yield
and 64% ee and 59% chemical yield and 46% ee, respec-
tively (Scheme 3). When 2-oxiranylethanol, which is far
away between the reactive site and the asymmetric car-
bon center, was used, the selectivity was very poor (run
1). Other various racemic primary alcohols having oxi-
4. Experimental
4.1. General
1H NMR data were collected on a JEOL NMR GSX-400
(399.6 MHz) spectrometer in deuteriochloroform with
tetramethylsilane used as an internal standard. The

1160
D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
0.3 mol%
Me
N
0.75 eq.
ArCOCl
N
Me
Bn
t-BuPh2SiCl / imidazole
O
OH
+
°
DMF
i-Pr2NEt (0.5 eq.) / MS 4A
CH2Cl2 - DMF (9 : 1)
-78 °C / 3 h
Ar = α-naphthyl
( )
O
O
OCOAr
+
OSiPh2t-Bu
5
6
36%, 64% ee
s = 6.4
59%, 46% ee
Scheme 3. Kinetic resolution of glycidol.
Table 3. Kinetic resolution of various racemic primary alcohols
0.3 mol%
N
Me
0.75 eq.
N
Bn
Me
RCH2OH
( )
RCH2OH
ArCOCl
+
RCH2OCOAr
+
°
i-Pr2NEt (0.5 eq.) / MS 4A
CH2Cl2 / -78 °C / 3 h
7a-g
8a-g
Run
Alcohol
Ar
Ester 7a–g
Alcohol 8a–g
Yield/%
s
Yield/%
Eea/%
11
Eea/%
12
O
1
4-MeC6H4
49 (7a)
52 (7b)
42 (8a)b
40 (8b)
1.4
4.0
OH
O
2c
4-t-BuC6H4
44
47
Ph
OH
OH
O
3c
4c
5
Ph
50 (7c)
42 (7d)
48 (7e)
43
32
50
45 (8c)
31 (8d)
47 (8e)b
48
3.7
2.4
4.6
Ph
Ph
32d
46
TsN
OH
OH
4-MeC6H4
O
6
4-MeC6H4
Ph
50 (7f)
51 (7g)
41
2
37 (8f)b
49 (8g)
41
3
3.5
1.1
OH
OH
O
7c
Ph
a Determined by HPLC analysis with a chiral column.
b Unreacted alcohol was isolated as a corresponding t-butyldiphenylsilyl ether.
c 0.6 equiv of acyl chloride was used.
d Determined by HPLC analysis with a chiral column after converted to the corresponding benzoate.
enantiomeric ratios of the esters were determined using
HPLC through Daicel Chiralpak AD or Daicel Chiralcel
OD column (1.0 mL/min, 254 nm). Optical rotations
were measured by JASCO DIP-1000 polarimeter using
a sodium lamp (589 nm). CH2Cl2 was distilled over
CaH2 after dried up with P2O5. DMF was distilled over
1H, J = 8.0, 9.6 Hz), 2.20 (s, 3H), 2.29–2.35 (m, 2H),
2.38 (s, 3H), 2.51–2.55 (m, 1H), 3.01–3.05 (m, 1H), 3.43
(d, 1H, J = 13.2 Hz), 3.56 (d, 1H, J = 13.2 Hz), 7.22–
7.32 (m, 5H); 13C NMR: d 22.43 (CH2), 30.70 (CH2),
41.35 (CH3), 43.01 (CH3), 57.74 (CH2), 62.56 (CH2),
63.15 (CH), 63.69 (CH2), 126.84 (CH), 128.10 (CH),
128.99 (CH), 139.19 (C).
˚
P2O5. MS 4 A was used as a powder.
4.2. Chiral 1,2-diamine9
4.3. Typical procedure for the preparation of glycerol
derivatives
4.2.1. (S)-1-Methyl-2-[(benzylmethylamino)methyl]pyr-
1
rolidine. [a]D = À83 (c 1.0, EtOH), H NMR: d 1.55
To a solution of glycerol (9.17 g, 99.6 mmol) and imid-
azole (40.9 g, 600 mmol) in DMF (120 mL) was added
(m, 1H), 1.67–1.74 (m, 2H), 1.98–2.03 (m, 1H), 2.16 (dt,

D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
1161
trimethylsilyl chloride (60 mL, 500 mmol) at 0 °C under
argon atmosphere. After being stirred for 5 h at room
temperature, it was quenched with satd NaHCO3 aq at
0 °C. The organic materials were extracted with ether
and the combined extracts washed with brine, dried over
anhydrous magnesium sulfate, and concentrated in
vacuo. The crude products were purified by distillation
under reduced pressure to yield 23.9 g of tris(trimethyl-
silyl)glycerol (78%).
4.3.4. (2,2-Dicyclohexyl-[1,3]dioxolan-4-yl)-methanol 1f.
1H NMR: d 1.04–1.23 (m, 10H), 1.64–1.77 (m, 13H),
3.57 (dd, 1H, J = 7.3, 8.8 Hz), 3.65–3.73 (m, 2H), 4.08
(t, 1H, J = 7.3 Hz), 4.26–4.33 (m, 1H); 13C NMR: d
26.54 (CH2), 27.25 (CH2), 43.31 (CH2), 44.55 (CH),
63.49 (CH2), 68.38 (CH2), 78.16 (CH), 116.27 (C).
4.3.5. (2,2-Dibenzyl-[1,3]dioxolan-4-yl)-methanol 1g.
1H NMR: d 2.94–3.04 (m, 5H), 3.33 (t, 1H, J =
7.3 Hz), 3.40 (dd, 1H, J = 2.6, 12.1 Hz), 3.67 (t, 1H,
J = 7.3 Hz), 3.70–3.76 (m, 1H), 7.22–7.32 (m, 10H);
13C NMR: d 44.08 (CH2), 45.17 (CH2), 62.06 (CH2),
66.04 (CH2), 76.76 (CH), 111.33 (C), 126.52 (CH),
126.70 (CH), 127.96 (CH), 128.04 (CH), 130.62 (CH),
130.98 (CH), 136.09 (C), 136.41 (C).
To a solution of tris(trimethylsilyl)glycerol (2.36 g,
7.64 mmol) and dibenzyl ketone (1.34 g, 6.37 mmol) in
dichloromethane (7 mL) was added trimethylsilyl trifluo-
romethanesulfonate (72.2 mg, 0.32 mmol) in dichloro-
methane (3 mL) at À78 °C under an argon atmosphere.
After being stirred for 2 h at À78 °C and then addition-
ally stirred for 6 h at À20 °C and at room temperature
for 14 h, triethylamine (1.2 mL) was added and quenched
with 10% aq NaOH. The organic materials were ex-
tracted with ether and the combined extracts washed
with brine, dried over anhydrous magnesium sulfate,
and concentrated in vacuo. To a solution of crude prod-
ucts in THF was added TBAF in THF (1 M, 7 mL) and
stirred for 30 min. The organic materials were extracted
with ether and the combined extracts were washed with
brine, dried over anhydrous magnesium sulfate, and con-
centrated in vacuo. The crude products were purified by
silica gel column chromatography to yield 1.57 g of (2,2-
dibenzyl-[1,3]dioxolan-4-yl)methanol (87%).
4.4. Chiral esters of primary alcohol
4.4.1. (R)-4-Benzoyloxymethyl-2,2-dimethyl-1,3-dioxo-
lane 2a. HPLC: Daicel Chiralcel OD (i-PrOH/
hexane = 1/100, tR = 9.6 min (À), 10.9 min (+)), 56%
ee, [a]D = +4.0 (c 1.0, CHCl3), 1H NMR: d 1.39 (s,
3H), 1.46 (s, 3H), 3.88 (dd, 1H, J = 5.9, 8.4 Hz), 4.15
(dd, 1H, J = 6.6, 8.4 Hz), 4.36 (dd, 1H, J = 5.5,
11.4 Hz), 4.41 (dd, 1H, J = 4.8, 11.4 Hz), 4.43–4.57 (m,
1H), 7.43–7.46 (m, 2H), 7.55–7.59 (m, 1H), 8.05–8.07
(m, 2H); 13C NMR: d 25.42 (CH3), 26.76 (CH3), 65.03
(CH2), 66.41 (CH2), 73.67 (CH), 109.80 (C), 128.32
(CH), 129.60 (CH), 129.65 (CH), 133.04 (C), 166.20 (C).
(2,2-Dicyclohexyl-[1,3]dioxolan-4-yl)-methanol and (2,2-
diphenyl-[1,3]dioxolan-4-yl)methanol were prepared
similarly as mentioned above using the corresponding
ketones, respectively. Other glycerol derivatives were
prepared from glycerol and the corresponding ketones
under classical acidic conditions.14
4.4.2. 4-Benzoyloxymethyl-2,2-di-n-propyl-1,3-dioxolane
2b. HPLC: Daicel Chiralcel OD (i-PrOH/hexane =
1/100, tR = 6.6 min (À), 7.5 min (+)), 60% ee, [a]D =
1
+11.9 (c 1.0, CHCl3), H NMR: d 0.88 (td, 3H, J = 1.1,
7.3 Hz), 0.93 (td, 3H, J = 1.1, 7.3 Hz), 1.34–1.46 (m,
4H), 1.58–1.66 (m, 4H), 3.82 (td, 1H, J = 1.5, 6.6 Hz),
4.14 (td, 1H, J = 1.5, 6.2 Hz), 4.35–4.47 (m, 3H), 7.43–
7.47 (m, 2H), 7.55–7.59 (m, 1H), 8.08 (dt, 2H, J = 1.3,
8.4 Hz); 13C NMR: d 14.32 (CH3), 16.96 (CH2), 17.23
(CH2), 39.34 (CH2), 39.75 (CH2), 64.78 (CH2), 66.79
(CH2), 73.85 (CH), 113.13 (C), 128.37 (CH), 129.70
(CH), 129.83 (CH), 133.13 (C), 166.35 (C).
4.3.1. (2,2-Di-n-propyl-[1,3]dioxolan-4-yl)-methanol 1b. 1H
NMR: d 0.92 (t, 3H, J = 7.3 Hz), 0.92 (t, 3H, J = 7.3 Hz),
1.32–1.45 (m, 4H), 1.56–1.65 (m, 4H), 1.89 (br, 1H), 3.56–
3.62 (m, 1H), 3.71–3.78 (m, 2H), 4.03 (dd, 1H, J = 6.6,
8.1 Hz), 4.19–4.25 (m, 1H); 13C NMR: d 14.41 (CH3),
17.03 (CH2), 17.33 (CH2), 39.19 (CH2), 39.67 (CH2),
62.99 (CH2), 65.97 (CH2), 76.24 (CH), 112.59 (C).
4.4.3. 4-Benzoyloxymethyl-2,2-di-n-butyl-1,3-dioxolane
2c. HPLC: Daicel Chiralcel OD (i-PrOH/hexane =
1/100, tR = 6.4 min (À), 7.0 min (+)), 54% ee,
1
[a]D = +10.7 (c 1.0, CHCl3), H NMR: d 0.84–0.93 (m,
4.3.2. (2,2-Di-n-butyl-[1,3]dioxolan-4-yl)-methanol 1c.
1H NMR: d 0.91 (t, 6H, J = 6.6 Hz), 1.26–1.39 (m,
8H), 1.58–1.66 (m, 4H), 1.87 (br, 1H), 3.60 (dd, 1H,
J = 5.1, 11.7 Hz), 3.72–3.78 (m, 2H), 4.03 (dd, 1H,
J = 6.6, 8.1 Hz), 4.20–4.25 (m, 1H); 13C NMR: d 14.11
(CH3), 23.02 (CH2), 25.92 (CH2), 26.22 (CH2), 36.61
(CH2), 37.16 (CH2), 62.99 (CH2), 65.90 (CH2), 76.21
(CH), 112.76 (C).
6H), 1.23–1.40 (m, 8H), 1.59–1.68 (m, 4H), 3.84 (dd,
1H, J = 6.2, 8.1 Hz), 4.14 (dd, 1H, J = 6.2, 8.1 Hz),
4.36–4.48 (m, 3H), 7.44 (t, 2H, J = 7.5 Hz), 7.57 (tt,
1H, J = 1.5, 7.3 Hz), 8.06 (dt, 2H, J = 1.5, 8.4 Hz); 13C
NMR: d 14.10 (CH3), 23.02 (CH2), 25.86 (CH2), 26.18
(CH2), 36.83 (CH2), 37.27 (CH2), 64.65 (CH2), 66.73
(CH2), 73.81 (CH), 113.18 (C), 128.30 (CH), 129.62
(CH), 129.66 (CH), 133.06 (C), 166.22 (C).
4.3.3. (2,2-Diisopropyl-[1,3]dioxolan-4-yl)-methanol 1e.
1H NMR: d 0.92–0.95 (m, 12H), 1.88 (br, 1H),
2.04–2.13 (m, 2H), 3.64 (dd, 1H, J = 7.3, 8.8 Hz),
3.65–3.76 (m, 2H), 4.12 (t, 1H, J = 7.3 Hz), 4.30–4.36
(m, 1H); 13C NMR: d 17.42 (CH3), 33.58 (CH), 34.67
(CH), 63.45 (CH2), 68.40 (CH2), 78.12 (CH), 116.97
(C).
4.4.4. (R)-2-Benzoyloxymethyl-1,4-dioxa-spiro[4.5]dec-
ane 2d. HPLC: Daicel Chiralcel OD (i-PrOH/hex-
ane = 1/100, tR = 8.5 min (À), 9.8 min (+)), 53% ee,
1
[a]D = +6.5 (c 1.0, CHCl3), H NMR: d 1.34–1.48 (m,
2H), 1.58–1.68 (m, 8H), 3.88 (dd, 1H, J = 5.9, 8.4 Hz),
4.14 (dd, 1H, J = 6.2, 8.4 Hz), 4.38 (d, 2H, J = 4.8 Hz),
4.41–4.48 (m, 1H), 7.43–7.47 (m, 2H), 7.55–7.59 (m,

1162
D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
1H), 8.06 (dt, 2H, J = 1.5, 8.4 Hz); 13C NMR: d 23.79
(CH2), 23.93 (CH2), 25.07 (CH2), 34.89 (CH2), 36.36
(CH2), 65.11 (CH2), 66.11 (CH2), 73.27 (CH), 110.39
(C), 128.41 (CH), 129.68 (CH), 129.84 (CH), 133.10
(C), 166.32 (C).
(CH3), 17.49 (CH3), 21.72 (CH3), 33.65 (CH), 34.64
(CH), 64.87 (CH2), 69.49 (CH2), 75.39 (CH), 117.14
(CH), 125.70 (CH), 130.68 (CH), 131.71 (CH), 132.15
(C), 140.33 (C), 167.27 (C).
4.4.10. (R)-4-(m-Toluoyl)oxymethyl-2,2-diisopropyl-1,3-
dioxolane 4c. HPLC: Daicel Chiralcel OD (i-PrOH/
hexane = 1/100, tR = 6.0 min (À), 7.0 min (+)), 51% ee,
4.4.5. (R)-4-Benzoyloxymethyl-2,2-diisopropyl-1,3-dioxo-
lane 2e. HPLC: Daicel Chiralcel OD (i-PrOH/hex-
ane = 1/100, tR = 6.3 min (À), 7.8 min (+)), 59% ee,
1
[a]D = +8.6 (c 1.0, CHCl3), H NMR: d 0.94–0.97 (m,
1
[a]D = +8.9 (c 1.0, CHCl3), H NMR: d 0.93–0.97 (m,
12H), 2.05–2.31 (m, 2H), 3.77 (dd, 1H, J = 7.7,
8.4 Hz), 4.24 (dd, 1H, J = 6.6, 7.7 Hz), 4.40 (dd, 1H,
J = 5.0, 11.4 Hz), 4.47 (dd, 1H, J = 5.1, 11.4 Hz), 4.50–
4.56 (m, 1H), 7.31–7.52 (m, 2H), 7.83–8.06 (m, 2H);
13C NMR: d 17.36 (CH3), 17.39 (CH3), 17.47 (CH3),
21.23 (CH3), 33.68 (CH), 34.66 (CH), 64.83 (CH2),
69.30 (CH2), 75.44 (CH), 117.32 (CH), 126.87 (CH),
128.26 (CH), 130.25 (CH), 133.89 (C), 138.18 (C),
166.56 (C).
12H), 2.07–2.14 (m, 2H), 3.77 (t, 1H, J = 7.7 Hz), 4.24
(dd, 1H, J = 6.6, 7.7 Hz), 4.39–4.57 (m, 3H), 7.43–7.47
(m, 2H), 7.55–7.59 (m, 1H), 8.04–8.07 (m, 2H); 13C
NMR: d 17.34 (CH3), 17.42 (CH3), 33.64 (CH2), 34.63
(CH2), 64.90 (CH2), 69.28 (CH2), 75.40 (CH), 117.35
(C), 128.37 (CH), 129.72 (CH), 133.13 (C), 166.35 (C).
4.4.6. 4-Benzoyloxymethyl-2,2-dicyclohexyl-1,3-dioxo-
lane 2f. HPLC: Daicel Chiralpak AD (i-PrOH/hex-
ane = 1/20, tR = 8.3 min (À), 11.0 min (+)), 51% ee,
4.4.11. (R)-4-(p-Toluoyl)oxymethyl-2,2-diisopropyl-1,3-
dioxolane 4d. HPLC: Daicel Chiralcel OD (i-PrOH/
hexane = 1/20, tR = 5.3 min (À), 9.4 min (+)), 68% ee,
1
[a]D = +7.5 (c 1.0, CHCl3), H NMR: d 1.04–1.23 (m,
10H), 1.61–1.84 (m, 12H), 3.73 (t, 1H, J = 8.1 Hz),
4.19 (t, 1H, J = 7.1 Hz), 4.44–4.52 (m, 3H), 7.43–7.47
(m, 2H), 7.55–7.60 (m, 1H), 8.04–8.07 (m, 2H); 13C
NMR: d 26.48 (CH2), 27.14 (CH2), 43.33 (CH2), 44.39
(CH), 64.54 (CH2), 69.03 (CH2), 75.45 (CH), 116.57
(C), 128.27 (CH), 129.58 (CH), 129.70 (CH), 133.04
(C), 166.25 (C).
1
[a]D = +10.4 (c 1.0, CHCl3), H NMR: d 0.90–0.99 (m,
12H), 2.07–2.14 (m, 2H), 2.41 (s, 3H), 3.76 (t, 1H,
J = 8.2 Hz), 4.23 (dd, 1H, J = 6.8, 7.5 Hz), 4.37–4.49
(m, 1H), 4.50–4.55 (m, 1H), 7.24 (d, 2H, J = 8.1 Hz),
7.94 (dt, 2H, J = 1.8, 8.4 Hz); 13C NMR: d 17.36
(CH3), 17.39 (CH3), 17.47 (CH3), 18.51 (CH3), 21.68
(CH3), 33.68 (CH), 34.66 (CH), 64.71 (CH2), 69.33
(CH2), 75.47 (CH), 117.30 (CH), 127.03 (CH), 129.10
(CH), 129.19 (CH), 129.76 (C), 143.87 (C), 166.45 (C).
4.4.7.
4-Benzoyloxymethyl-2,2-dibenzyl-1,3-dioxolane
2g. HPLC: Daicel Chiralcel OD (i-PrOH/hexane =
1/20, tR = 13.7 min (À), 15.4 min (+)), 23% ee,
1
[a]D = +1.0 (c 1.0, CHCl3), H NMR: d 2.96 (m, 2H),
4.4.12. (R)-4-(p-t-Butylbenzoyl)oxymethyl-2,2-diisoprop-
yl-1,3-dioxolane 4e. HPLC: Daicel Chiralcel OD (i-
PrOH/hexane = 1/100, tR = 5.4 min (À), 7.1 min (+)),
2.99 (s, 2H), 3.22–3.27 (m, 1H), 3.67–3.72 (m, 1H),
3.82–3.92 (m, 3H), 7.21–7.30 (m, 10H), 7.41–7.45 (m,
2H), 7.54–7.58 (m, 1H), 7.98–8.00 (m, 2H); 13C NMR:
d 44.79 (CH2), 44.89 (CH2), 64.62 (CH2), 67.53 (CH2),
74.34 (CH), 112.20 (C), 126.49 (CH), 126.55 (CH),
127.82 (CH), 127.96 (CH), 128.36 (CH), 129.62 (CH),
129.78 (CH), 130.76 (CH), 131.01 (CH), 133.07 (CH),
136.04 (C), 136.37 (C), 166.08 (C).
1
57% ee, [a]D = +7.7 (c 1.0, CHCl3), H NMR: d 0.94–
0.96 (m, 12H), 1.34 (s, 9H), 2.05–2.16 (m, 2H), 3.76 (t,
1H, J = 8.1 Hz), 4.23 (t, 1H, J = 7.1 Hz), 4.39 (dd, 1H,
J = 4.8, 11.4 Hz), 4.67 (dd, 1H, J = 5.1, 11.4 Hz), 4.50–
4.55 (m, 1H), 7.46 (dt, 2H, J = 1.8, 8.8 Hz), 7.98 (dt,
2H, J = 1.8, 8.8 Hz); 13C NMR: d 17.36 (CH3), 17.41
(CH3), 17.49 (CH3), 31.10 (CH3), 33.68 (CH), 34.64
(CH), 35.10 (C), 64.73 (CH2), 69.35 (CH2), 75.47
(CH), 117.30 (CH), 125.37 (C), 126.96 (CH), 129.61
(CH), 156.85 (C), 166.38 (C).
4.4.8. (R)-4-Benzoyloxymethyl-2,2-diphenyl-1,3-dioxo-
lane 2h. HPLC: Daicel Chiralcel OD (i-PrOH/hex-
ane = 1/20, tR = 9.0 min (À), 10.1 min (+)), 54% ee,
1
[a]D = +16.7 (c 1.0, CHCl3), H NMR: d 4.04 (dd, 1H,
J = 6.2, 8.1 Hz), 4.17 (dd, 1H, J = 6.6, 8.4 Hz), 4.47 (d,
2H, J = 4.8 Hz), 4.56 (qui, 1H, J = 6.2 Hz), 7.23–7.42
(m, 8H), 7.49–7.57 (m, 5H), 7.95–7.97 (m, 2H); 13C
NMR: d 64.59 (CH2), 66.94 (CH2), 74.32 (CH), 110.30
(C), 126.13 (CH), 127.97 (CH), 128.06 (CH), 128.11
(CH), 128.25 (CH), 129.61 (CH), 133.00 (CH), 141.81
(CH), 166.14 (C).
4.4.13.
(R)-4-(p-Methoxybenzoyl)oxymethyl-2,2-diiso-
propyl-1,3-dioxolane 4f. HPLC: Daicel Chiralpak AD
(i-PrOH/hexane = 1/50, tR = 8.0 min (+), 8.7 min (À)),
1
70% ee, [a]D = +9.6 (c 1.0, CHCl3), H NMR: d 0.88–
0.96 (m, 12H), 2.06–2.14 (m, 2H), 3.76 (dd, 1H,
J = 7.9, 8.6 Hz), 3.87 (s, 3H), 4.23 (t, 1H, J = 7.3 Hz),
4.38 (dd, 1H, J = 4.9, 11.5 Hz), 4.44 (dd, 1H, J = 5.3,
11.5 Hz), 4.48–4.55 (m, 1H), 6.90–6.94 (m, 2H), 7.98–
8.02 (m, 2H); 13C NMR: d 17.44 (CH3), 17.53 (CH3),
33.69 (CH), 33.72 (CH), 34.66 (CH), 34.69 (CH), 65.44
(CH2), 69.60 (CH2), 75.49 (CH), 113.56 (CH), 117.20
(CH), 122.09 (CH), 131.71 (C), 163.38 (C), 165.95 (C).
4.4.9.
(R)-4-(o-Toluoyl)oxymethyl-2,2-diisopropyl-1,3-
dioxolane 4b. HPLC: Daicel Chiralpak AD (i-PrOH/
hexane = 1/1000, tR = 9.5 min (À), 10.4 min (+)), 61%
1
ee, [a]D = +6.1 (c 1.0, CHCl3), H NMR: d 0.93–0.96
(m, 12H), 2.04–2.14 (m, 2H), 2.60 (s, 3H), 3.74 (dd,
1H, J = 7.9, 8.6 Hz), 4.24 (dd, 1H, J = 7.0, 7.7 Hz),
4.36 (dd, 1H, J = 5.1, 11.4 Hz), 4.44 (dd, 1H, J = 5.9,
11.4 Hz), 4.49–4.56 (m, 1H), 7.23–7.24 (m, 2H), 7.39–
7.43 (m, 1H), 7.90–7.92 (m, 1H); 13C NMR: d 17.38
4.4.14. (R)-4-(p-Chlorobenzoyl)oxymethyl-2,2-diisoprop-
yl-1,3-dioxolane 4g. HPLC: Daicel Chiralcel OD (i-
PrOH/hexane = 1/20, tR = 4.8 min (À), 7.4 min (+)),
1
51% ee, [a]D = +5.4 (c 1.0, CHCl3), H NMR: d 0.93–

D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
1163
0.96 (m, 12H), 2.06–2.14 (m, 2H), 3.75 (t, 1H,
J = 8.2 Hz), 4.23 (t, 1H, J = 7.3 Hz), 4.41 (dd, 1H,
J = 4.8, 11.4 Hz), 4.47 (dd, 1H, J = 6.2, 11.4 Hz), 4.50–
4.55 (m, 1H), 7.40–7.44 (m, 2H), 7.97–8.00 (m, 2H);
13C NMR: d 17.34 (CH3), 17.38 (CH3), 17.46 (CH3),
17.49 (CH3), 33.65 (CH), 33.64 (CH), 65.09 (CH2),
69.14 (CH2), 75.36 (CH), 117.45 (CH), 128.23 (CH),
128.75 (CH), 131.11 (C), 139.65 (C), 165.51 (C).
46.87 (CH), 49.65 (CH2), 61.61 (CH2), 127.21 (C),
128.98 (CH), 129.45 (CH), 143.56 (C), 166.33 (C).
4.4.19. (S)-2-(4-t-Butylbenzoyloxymethyl)-3-phenyloxi-
rane 7b. HPLC: Daicel Chiralcel OD (i-PrOH/hex-
ane = 1/10, tR = 6.3 min (+), 23.9 min (À)), 44% ee,
1
[a]D = À13.7 (c 1.0, CHCl3), H NMR: d 1.33 (s, 9H),
3.37 (ddd, 1H, J = 2.2, 3.3, 5.5 Hz), 3.87 (d, 1H,
J = 1.8 Hz), 4.33 (dd, 1H, J = 5.9, 12.5 Hz), 4.71 (dd,
1H, J = 3.3, 12.5 Hz), 7.26–7.35 (m, 5H), 7.45 (dt, 2H,
J = 2.2, 8.8 Hz), 8.01 (dt, 2H, J = 2.2, 8.8 Hz); 13C
NMR: d 31.05 (CH3), 35.04 (C), 56.37 (CH), 59.43
(CH), 64.33 (CH2), 125.24 (CH), 125.56 (CH), 126.69
(C), 128.28 (CH), 128.37 (CH), 129.50 (CH), 136.14
(C), 156.72 (C), 166.00 (C).
4.4.15. (R)-4-a-Naphthoyloxymethyl-2,2-diisopropyl-1,3-
dioxolane 4h. HPLC: Daicel Chiralcel OD (i-PrOH/
hexane = 1/100, tR = 12.0 min (À), 13.2 min (+)), 81%
1
ee, [a]D = +5.9 (c 1.0, CHCl3), H NMR: d 0.93–0.98
(m, 12H), 2.09–2.17 (m, 2H), 3.79 (t, 1H, J = 8.1 Hz),
4.27 (t, 1H, J = 7.1 Hz), 4.48 (dd, 1H, J = 4.6,
11.2 Hz), 4.53–4.63 (m, 2H), 7.47–7.55 (m, 2H), 7.88
(d, 1H, J = 7.7 Hz), 8.02 (d, 1H, J = 8.1 Hz), 8.19 (dd,
1H, J = 1.5, 7.3 Hz), 8.91 (d, 1H, J = 8.8 Hz); 13C
NMR: d 17.47 (CH3), 17.58 (CH3), 33.71 (CH), 33.74
(CH), 65.15 (CH2), 69.42 (CH2), 75.43 (CH), 117.44
(CH), 124.37 (CH), 125.72 (C), 126.19 (CH), 126.64
(CH), 127.79 (CH), 128.51 (CH), 130.31 (CH), 131.30
(C), 133.55 (C), 133.75 (C), 167.12 (C). Anal. Calcd
for C21H26O4: C, 73.66; H, 7.65. Found: C, 73.26; H,
7.66.
4.4.20.
(S)-2-Benzoyloxymethyl-2-methyl-3-phenyloxi-
rane 7c. HPLC: Daicel Chiralcel OD (i-PrOH/hex-
ane = 1/100, tR = 10.9 min (+), 11.6 min (À)), 43% ee,
1
[a]D = À11.8 (c 1.0, CHCl3), H NMR: d 1.20 (s, 3H),
4.15 (s, 1H), 4.37 (d, 1H, J = 11.7 Hz), 4.59 (d, 1H,
J = 11.7 Hz), 7.29–7.38 (m, 5H), 7.43–7.47 (m, 2H),
7.55–7.59 (m, 1H), 8.08–8.11 (m, 2H); 13C NMR: d
13.87 (CH3), 61.24 (C), 61.66 (C), 68.34 (CH2),
126.40 (CH), 127.68 (CH), 128.08 (CH), 128.36 (CH),
129.60 (CH), 129.68 (C), 133.10 (CH), 134.99 (C),
166.01 (C).
4.4.16. (R)-4-b-Naphthoyloxymethyl-2,2-diisopropyl-1,3-
dioxolane 4i. HPLC: Daicel Chiralcel OD (i-PrOH/
hexane = 1/100, tR = 40.1 min (À), 71.0 min (+)), 78%
4.4.21.
(S)-2-Benzoyloxymethyl-1-tosylaziridine
7d.
1
ee, [a]D = +10.3 (c 1.2, CHCl3), H NMR: d 0.96–0.98
HPLC: Daicel Chiralpak AD (i-PrOH/hexane =
1/10, tR = 19.7 min (+), 21.5 min (À)), 32% ee,
(m, 12H), 2.09–2.18 (m, 2H), 3.82 (t, 1H, J = 8.1 Hz),
4.27 (t, 1H, J = 7.1 Hz), 4.48 (dd, 1H, J = 4.8,
11.4 Hz), 4.52–4.61 (m, 2H), 7.52–7.62 (m, 2H), 7.88
(d, 1H, J = 8.4 Hz), 7.95 (d, 1H, J = 8.1 Hz), 8.06 (dd,
1H, J = 1.5, 8.4 Hz), 8.62 (s, 1H); 13C NMR: d 17.47
(CH3), 17.57 (CH3), 33.72 (CH), 33.77 (CH), 34.69
(CH), 34.74 (CH), 64.97 (CH2), 69.28 (CH2), 75.48
(CH), 117.31 (CH), 125.13 (CH), 126.62 (CH), 126.90
(CH), 127.71 (CH), 128.28 (CH), 129.33 (CH), 131.20
(C), 132.36 (C), 135.51 (C), 166.41 (C).
1
[a]D = À8.2 (c 1.0, CHCl3), H NMR: d 2.32 (s, 1H),
2.33 (s, 3H), 2.84 (d, 1H, J = 6.6 Hz), 3.11–3.17 (m,
1H), 4.00 (dd, 1H, J = 7.3, 12.1 Hz), 4.52 (dd, 1H,
J = 4.0, 12.1 Hz), 7.22 (d, 2H, J = 8.1 Hz), 7.37–7.41
(m, 2H), 7.55–7.58 (m, 1H), 7.80–7.81 (m, 2H), 7.82–
7.84 (m, 2H); 13C NMR: d 21.61 (CH3), 30.56 (CH2),
37.75 (CH), 64.02 (CH2), 127.90 (CH), 127.95 (CH),
128.17 (CH), 129.22 (CH), 129.60 (C), 133.07 (CH),
134.53 (C), 144.55 (C), 165.70 (C).
4.4.17. (R)-a-Naphthoyloxymethyloxirane 5. HPLC:
Daicel Chiralcel OD (i-PrOH/hexane = 1/20, tR =
12.8 min (S), 14.3 min (R)), 64% ee, [a]D = À18.7 (c
1.0, CHCl3), 1H NMR: d 2.77 (dd, 1H, J = 2.7,
4.9 Hz), 2.92 (d, 1H, J = 4.4 Hz), 3.38–3.42 (m, 1H),
4.27 (dd, 1H, J = 6.0, 12.3 Hz), 4.74 (dd, 1H, J = 3.1,
12.3 Hz), 7.48–7.55 (m, 2H), 7.62 (td, 1H, J = 1.5,
7.0 Hz), 7.88 (d, 1H, J = 8.1 Hz), 8.03 (d, 1H,
J = 8.1 Hz), 8.24 (dd, 1H, J = 1.1, 7.0 Hz), 8.92 (dd,
1H, J = 0.7, 8.8 Hz); 13C NMR: d 44.82 (CH2), 49.51
(CH), 65.52 (CH2), 124.42 (CH), 125.64 (CH), 126.19
(CH), 126.32 (CH), 127.84 (CH), 128.54 (CH), 130.55
(CH), 131.30 (C), 133.59 (CH), 133.69 (CH), 166.92
(C).
4.4.22. 2-(p-Toluoyloxymethyl)tetrahydrofuran 7e. HPLC:
Chiralpak
Daicel
AD
(i-PrOH/hexane = 1/100,
tR = 25.5 min (À), 30.7 min (+)), 50% ee, [a]D = À13.3 (c
1
1.2, CHCl3), H NMR: d 1.68–1.77 (m, 2H), 1.87–2.01
(m, 2H), 2.03–2.11 (m, 1H), 2.41 (s, 3H), 3.81–3.86 (m,
1H), 3.91–3.96 (m, 1H), 4.24–4.30 (m, 2H), 4.34–4.40 (m,
1H), 7.23 (d, 2H, J = 8.1 Hz), 7.95 (dt, 2H, J = 1.8,
8.1 Hz); 13C NMR: d 21.63 (CH3), 25.74 (CH2), 28.10
(CH2), 66.75 (CH2), 68.53 (CH2), 129.02 (CH), 129.70
(CH), 143.63 (C), 166.62 (C).
4.4.23. 2-(p-Toluoyloxymethyl)tetrahydropyran 7f. HPLC:
Daicel Chiralcel OD (i-PrOH/hexane = 1/100, tR =
10.7 min (+), 12.4 min (À)), 41% ee, [a]D = À1.3 (c 1.0,
1
CHCl3), H NMR: d 1.37–1.68 (m, 5H), 1.88–1.91 (m,
4.4.18. p-Toluoyloxyethyloxirane 7a. HPLC: Daicel
Chiralpak AD (i-PrOH/hexane = 1/100, tR = 18.7 min
(À), 20.8 min (+)), 11% ee, [a]D = À6.6 (c 1.0, CHCl3),
1H NMR: d 1.91–2.09 (m, 2H), 2.40 (s, 3H), 2.56 (dd,
1H, J = 2.6, 4.8 Hz), 2.81 (t, 1H, J = 4.4 Hz), 3.08–3.13
(m, 1H), 4.45–4.48 (m, 2H), 7.22–7.24 (m, 2H), 7.91–
7.94 (m, 2H); 13C NMR: d 21.65 (CH3), 32.06 (CH2),
1H), 2.40 (s, 3H), 3.47 (dt, 1H, J = 2.6, 11.4 Hz), 3.64–
3.70 (m, 1H), 4.01–4.05 (m, 1H), 4.26 (dd, 1H, J = 5.8,
11.4 Hz), 4.29 (dd, 1H, J = 4.4, 11.4 Hz), 7.23 (d, 2H,
J = 8.4 Hz), 7.95 (dt, 2H, J = 2.2, 4.4 Hz); 13C NMR: d
21.71 (CH3), 23.07 (CH2), 25.86 (CH2), 28.12 (CH2),
67.68 (CH2), 68.43 (CH2), 75.57 (CH), 127.31 (C), 128.91
(CH), 129.67 (CH), 143.47 (C), 166.52 (C).

1164
D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
4.4.24. (2S,3S)-1-Benzoyloxymethyl-2-phenylcyclopro-
pane 7g. HPLC: Daicel Chiralcel OD (i-PrOH/hex-
ane = 1/20, tR = 6.2 min (+), 12.4 min (À)), 2% ee,
[a]D = +2.0 (c 1.0, CHCl3), 1H NMR: d 1.06 (t, 2H,
J = 7.0 Hz), 1.58–1.65 (m, 2H), 1.97–2.01 (m, 1H),
4.28–4.37 (m, 2H), 7.08–7.11 (m, 2H), 7.14–7.18 (m,
1H), 7.24–7.28 (m, 2H), 7.42–7.45 (m, 2H), 7.53–7.57
(m, 1H), 8.04–8.07 (m, 2H); 13C NMR: d 13.95
(CH2), 21.56 (CH), 21.88 (CH), 68.42 (CH2), 125.75
(CH), 125.99 (CH), 128.28 (CH), 129.49 (CH),
129.62 (CH), 130.30 (C), 132.82 (CH), 141.89 (C),
166.58 (C).
4.5.9. (R)-trans-3-Phenylglycidol 8b. HPLC: Daicel
Chiralcel OD (i-PrOH/hexane = 1/20, tR = 21.4 min
(À), 24.3 min (+)), 47% ee, [a]D = +24.1 (c 1.8, CHCl3)
{lit.16 (R)-configuration [a]D = +45.9 (c 1.5, EtOH)}.
4.5.10. (R)-trans-2-Methyl-3-phenylglycidol 8c. HPLC:
Daicel Chiralcel OD (i-PrOH/hexane = 1/20, tR = 10.2
min (À), 13.5 min (+)), 48% ee, [a]D = +9.1 (c 1.8, CHCl3)
{lit.16 (S)-configuration [a]D = À16.9 (c 2.0, CHCl3)}.
4.5.11. (S)-1-Tosylaziridine-2-methanol 8d. HPLC:
Daicel Chiralpak AD (i-PrOH/hexane = 1/10, tR =
20.9 min (+), 22.8 min (À)), 32% ee, [a]D = À10.9 (c
1.0, CHCl3) {lit.17 (R)-configuration [a]D = +29.9 (c
9.9, EtOAc)}.
4.5. Chiral primary alcohols
4.5.1. (R)-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-methanol 3a.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane = 1/100,
tR = 9.6 min (À), 11.0 min (+)), 69% ee (measured
after converted to benzoate), [a]D = À6.6 (c 1.32,
MeOH) {lit.13 (S)-configuration; [a]D = +6.7 (c 0.0025,
hexane)}.
4.5.12. (2R,3R)-2-Phenylcyclopropane-1-methanol 8g.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane = 1/20,
tR = 13.1 min (+), 19.0 min (À)), 3% ee, [a]D = À2.2 (c
2.1, EtOH) {lit.18 (2R,3R)-configuration [a]D = +92.0
(c 1.23, EtOH)}.
4.5.2. (2,2-Di-n-propyl-[1,3]dioxolan-4-yl)-methanol 3b.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane =
1/100, tR = 6.5 min (À), 7.4 min (+)), 64% ee (measured
after converted to benzoate), [a]D = À3.3 (c 1.01,
CHCl3).
4.6. Chiral silyl ethers of primary alcohol
4.6.1.
(S)-t-Butyldiphenylsilyloxymethyloxirane
6.
HPLC: Daicel Chiralpak AD (i-PrOH/hexane =
1/1000, tR = 6.2 min (À), 7.8 min (+)), 46% ee, [a]D =
À1.4 (c 1.0, CHCl3) {lit.16 (S)-configuration [a]D = À2.3
(c 9.07, CHCl3)}.
4.5.3. (2,2-Di-n-butyl-[1,3]dioxolan-4-yl)-methanol 3c.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane = 1/100,
tR = 6.5 min (À), 7.1 min (+)), 71% ee (measured after
converted to benzoate), [a]D = À3.2 (c 0.99, CHCl3).
4.6.2. t-Butyldiphenylsilyloxyethyloxirane 8a. HPLC:
Daicel Chiralcel OD (i-PrOH/hexane = 1/100, tR =
5.1 min (+), 6.2 min (À)), 12% ee, [a]D = +1.6 (c 1.0,
CHCl3), 1H NMR: d 1.06 (s, 9H), 1.77 (q, 2H,
J = 5.9 Hz), 2.51 (dd, 1H, J = 2.6, 5.1 Hz), 2.78 (t, 1H,
J = 4.8 Hz), 3.08–3.12 (m, 1H), 3.79 (dd, 1H, J = 5.9,
10.6 Hz), 3.85 (dd, 1H, J = 6.2, 10.3 Hz), 7.36–7.44 (m,
6H), 7.66–7.67 (m, 4H); 13C NMR: d 19.23 (C), 26.85
(CH3), 35.72 (CH2), 47.28 (CH), 50.13 (CH2), 60.89
(CH2), 127.59 (CH), 129.57 (CH), 133.51 (C), 133.57
(C), 135.43 (CH), 135.45 (CH).
4.5.4. (R)-(1,4-Dioxa-spiro[4.5]dec-2-yl)-methanol 3d.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane =
1/100, tR = 8.6 min (À), 9.8 min (+)), 65% ee (measured
after converted to benzoate), [a]D = À3.8 (c 0.09,
MeOH) {lit.13 (S)-configuration [a]D = +6.8 (c 0.0118,
MeOH)}.
4.5.5. (R)-(2,2-Diisopropyl-[1,3]dioxolan-4-yl)-methanol
3e. HPLC: Daicel Chiralcel OD (i-PrOH/hexane = 1/
100, tR = 6.1 min (À), 7.3 min (+)), 75% ee (measured
after converted to benzoate), [a]D = À13.7 (c 1.02,
CHCl3) {lit.15 (S)-configuration [a]D = +0.4 (c 1.5,
MeOH)}.
4.6.3. 2-(t-Butyldiphenylsilyloxymethyl)tetrahydrofuran
8e. HPLC: Daicel Chiralpak AD (i-PrOH/hex-
ane = 1/1000, tR = 6.2 min (+), 7.3 min (À)), 46% ee,
1
[a]D = +2.6 (c 1.4, CHCl3), H NMR: d 1.06 (s, 9H),
1.74–1.98 (m, 4H), 3.62 (dd, 1H, J = 4.9, 10.4 Hz),
3.67 (dd, 1H, J = 4.9, 10.4 Hz), 3.75–3.80 (m, 1H),
3.82–3.87 (m, 1H), 4.01–4.07 (m, 1H), 7.35–7.42 (m,
6H), 7.67–7.70 (m, 4H); 13C NMR: d 19.24 (C), 25.82
(CH2), 26.83 (CH3), 27.86 (CH2), 66.42 (CH2), 68.43
(CH2), 79.29 (CH), 127.61 (CH), 129.56 (CH), 133.70
(C), 135.63 (CH).
4.5.6. (2,2-Dicyclohexyl-[1,3]dioxolan-4-yl)-methanol 3f.
HPLC: Daicel Chiralpak AD (i-PrOH/hexane =
1/20, tR = 8.0 min (À), 11.2 min (+)), 82% ee (measured
after converted to benzoate), [a]D = À5.9 (c 1.05,
CHCl3).
4.5.7. (2,2-Dibenzyl-[1,3]dioxolan-4-yl)-methanol 3g.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane = 1/20,
tR = 14.2 min (À), 15.9 min (+)), 29% ee, [a]D = À2.4
(c 1.03, CHCl3).
4.6.4. 2-(t-Butyldiphenylsilyloxymethyl)tetrahydropyran
8f. HPLC: Daicel Chiralcel OD (i-PrOH/hexane =
1/1000, tR = 7.6 min (+), 9.5 min (À)), 41% ee, [a]D =
1
À3.0 (c 1.0, CHCl3), H NMR: d 1.05 (s, 9H), 1.21–
4.5.8. (R)-(2,2-Diphenyl-[1,3]dioxolan-4-yl)-methanol 3h.
HPLC: Daicel Chiralcel OD (i-PrOH/hexane = 1/20,
tR = 14.8 min (À), 16.1 min (+)), 62% ee, [a]D = À24.5
(c 0.95, CHCl3) {lit.13 (S)-configuration [a]D = +22.5 (c
0.0036, MeOH)}.
1.32 (m, 1H), 1.41–1.62 (m, 3H), 1.71 (d, 1H,
J = 12.8 Hz), 1.84 (d, 1H, J = 11.7 Hz), 3.38–3.44 (m,
2H), 3.52 (dd, 1H, J = 5.9, 10.3 Hz), 3.71 (dd, 1H,
J = 5.5, 10.3 Hz), 3.94–3.97 (m, 1H), 7.35–7.43 (m,
6H), 7.66–7.68 (m, 4H); 13C NMR: d 19.35 (C), 23.19

D. Terakado et al. / Tetrahedron: Asymmetry 16 (2005) 1157–1165
1165
Chem. Res. 2000, 33, 412–420; (g) Fu, G. C. Acc. Chem.
Res. 2004, 37, 542–547.
(CH2), 26.25 (CH2), 26.92 (CH3), 28.65 (CH2), 67.42
(CH2), 68.34 (CH2), 78.16 (CH), 127.50 (CH), 129.46
(CH), 133.65 (C), 133.69 (C), 135.54 (CH).
5. (a) Miller, S. J.; Copeland, G. T.; Papaioannou, N.;
Horstmann, T. E.; Ruel, E. M. J. Am. Chem. Soc. 1998,
120, 1629–1630; (b) Copeland, G. T.; Jarvo, E. R.; Miller,
S. J. J. Org. Chem. 1998, 63, 6784–6785; (c) Jarvo, E. R.;
Copeland, G. T.; Papaioannou, N.; Bonitatebus, P. J., Jr.;
Miller, S. J. J. Am. Chem. Soc. 1999, 121, 11638–11643; (d)
Jarvo, E. R.; Vasbinder, M. M.; Miller, S. J. Tetrahedron
2000, 56, 9773–9779; (e) Jarvo, E. R.; Evans, C. A.;
Copeland, G. T.; Miller, S. J. J. Org. Chem. 2001, 66,
5522–5527.
6. (a) Spivey, A. C.; Fekner, T.; Spey, S. E. J. Org. Chem.
2000, 65, 3154–3159; (b) Spivey, A. C.; Maddaford, A.;
Fekner, T.; Redgrave, A. J.; Frampton, C. S. J. Chem.
Soc., Perkin Trans. 1 2000, 3460–3468; (c) Spivey, A. C.;
Maddaford, A.; Leese, D. P.; Redgrave, A. J. J. Chem.
Soc., Perkin Trans. 1 2001, 1785–1794; (d) Spivey, A. C.;
Zhu, F.; Mitchell, M. B.; Davey, S. G.; Jarvest, R. L. J.
Org. Chem. 2003, 68, 7379–7385; (e) Spivey, A. C.; Leese,
D. P.; Zhu, F.; Davey, S. G.; Jarvest, R. L. Tetrahedron
2004, 60, 4513–4525.
4.7. Typical procedure of the kinetic resolution of racemic
primary alcohol
˚
To molecular sieves 4 A (40 mg) were added a solution
of (S)-1-methyl-2-[(benzylmethylamino)methyl]pyrrol-
idine (0.2 mg, 0.92 lmol) in CH2Cl2 (0.2 mL), a solution
of diisopropylethylamine (19.7 mg, 0.152 mmol) in
CH2Cl2 (0.5 mL), a solution of (2,2-diisopropyl-[1,3]-
dioxolane-4-yl)-methanol (57.2 mg, 0.304 mmol) in
CH2Cl2 (0.8 mL) and a solution of a-naphthoyl chloride
(43.4 mg, 0.228 mmol) in CH2Cl2 (0.3 mL) and DMF
(0.2 mL) sequentially at À78 °C under an argon atmo-
sphere. The reaction was quenched after 3 h at À78 °C
by the addition of a phosphate buffer (pH 7). The organ-
ic materials were extracted with ether and the combined
extracts were washed with brine, dried over anhydrous
magnesium sulfate, and concentrated in vacuo. The
crude products were purified by TLC to yield 37.7 mg
of 4-a-naphthoyloxymethyl-2,2-diisopropyl-1,3-dioxolane
{38%, 81% ee, [a]D = +5.2 (c 1.0, CHCl3)} and 28.5 mg
of (2,2-diisopropyl-[1,3]-dioxolane-4-yl)-methanol {50%,
48% ee, [a]D = À10.3 (c 0.9, MeOH)}.
7. (a) Kawabata, T.; Nagato, M.; Takasu, K.; Fuji, K. J.
Am. Chem. Soc. 1997, 119, 3169–3170; (b) Kawabata, T.;
Yamamoto, K.; Momose, Y.; Yoshida, H.; Nagaoka, Y.;
Fuji, K. Chem. Commun. 2001, 2700–2701; (c) Kawabata,
T.; Stragies, R.; Fukaya, T.; Nagaoka, Y.; Schedel, H.;
Fuji, K. Tetrahedron Lett. 2003, 44, 1545–1548; (d)
Naraku, J.; Shimomoto, N.; Hanamoto, T.; Inanaga, J.
Enantiomer 2000, 5, 135–138.
8. Matsumura, Y.; Maki, T.; Murakami, S.; Onomura, O.
J. Am. Chem. Soc. 2003, 125, 2052–2053.
Acknowledgements
9. (a) Oriyama, T.; Imai, K.; Hosoya, T.; Sano, T.
Tetrahedron Lett. 1998, 39, 397–400; (b) Oriyama, T.;
Imai, K.; Sano, T.; Hosoya, T. Tetrahedron Lett. 1998,
39, 3529–3532; (c) Oriyama, T.; Hosoya, T.; Sano, T.
Heterocycles 2000, 52, 1065–1069; (d) Oriyama, T.;
Taguchi, H.; Terakado, D.; Sano, T. Chem. Lett. 2002,
31, 26–27.
This work was supported by a Grant-in-Aid for Scien-
tific Research on Priority Area (A) ÔExploitation of
Multi-Element Cyclic MoleculesÕ from the Ministry of
Education, Culture, Sports, Science, and Technology,
Japan.
10. (a) Oriyama, T.; Hori, Y.; Imai, K.; Sasaki, R. Tetrahe-
dron Lett. 1996, 37, 8543–8546; (b) Sano, T.; Imai, K.;
Ohashi, K.; Oriyama, T. Chem. Lett. 1999, 28, 265–266;
(c) Sano, T.; Miyata, H.; Oriyama, T. Enantiomer 2000, 5,
119–123.
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