Enantioselective alkylation of aldehydes using dialkylzincs catalyzed by simple chiral diols derived from naturally occurring monosaccharides

Article abstract of DOI:10.1016/j.tet.2013.03.090

Enantioselective alkylation of aldehydes was achieved in up to 84% ee using dialkylzincs catalyzed by simple diols derived from naturally occurring monosaccharides.

Full text of DOI:10.1016/j.tet.2013.03.090

Tetrahedron 69 (2013) 4221e4225
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Enantioselective alkylation of aldehydes using dialkylzincs catalyzed
by simple chiral diols derived from naturally occurring
monosaccharides
*
Kyosuke Michigami, Masahiko Hayashi
Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Enantioselective alkylation of aldehydes was achieved in up to 84% ee using dialkylzincs catalyzed by
simple diols derived from naturally occurring monosaccharides.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 31 January 2013
Received in revised form 22 March 2013
Accepted 23 March 2013
Available online 28 March 2013
Keywords:
Alkylation
Chiral diol
Monosaccharide
Enantioselectivity
1. Introduction
2. Results and discussion
Enantioselective alkylation of aldehydes with dialkylzincs cata-
lyzed by -amino alcohols is one of the most established methods to
obtain optically active secondary alcohols. Since the pioneering
work of Oguni, Noyori, and Soai, there have been many reports on
As mentioned above, chiral diols are often used in combination
with Ti(O-i-Pr)4. Therefore, we first examined the effect of Ti(O-i-
Pr)4 in the reaction of benzaldehyde with diethylzinc. We found
that addition of Ti(O-i-Pr)4 decreased both reactivity and enantio-
selectivity. Next, we examined the nature of the chiral diols (1e8)
derived from monosaccharides in the enantioselective ethylation of
benzaldehyde. These chiral diols derived from monosaccharides
were prepared by the complete cleavage of the benzylidene acetals
using NaHSO4$H2O in MeOH.
b
the development of
b
-amino alcohol type catalysts to be used in
these reactions.1e3 However, most of the
b-amino alcohols used are
not always easy to prepare. We have recently established simple
synthetic method to prepare (ꢀ)-1-piperidino-3,3-dimethyl-2-
butanol ((ꢀ)-PDB).4 Alternatively, C2 symmetric chiral diols
(e.g., TADDOL, BINOL)5 and disulfonamides6 have been used in the
combination with Ti(O-i-Pr)4 to afford the alkylation product in
high ee. On the other hand, there have been some reports on
asymmetric reactions using carbohydrate-derived ligands.7,8
One example for preparation of 1 is shown in Scheme 1.9 As
shown in Table 1, the configurations of configuration and the only
difference between ligands 6 and 7 is the kind of protecting group.
Among the chiral diols we examined,
a-methyl-2,3-O-methyl-
D-
Monosaccharides, such as
D-glucose,
D-mannose, and
D-galactose
glycopyranoside (3) and -methyl-2,3-O-methyl-
a
D-mannopyrano-
exist widely in nature. Therefore, monosaccharides with amino
acids as chiral sources are attractive molecules. Our purpose was to
side (5) gave the ethylated product in high ee (81% ee and 84% ee,
respectively). Asymmetric ethylation using ligand 1 at 0 ꢁC for 24 h
provided the product in 89% yield (46% ee). Thus, we concluded that
prepare chiral diols from monosaccharides, such as
D-glucose,
D
-mannose, and -galactose and examine them as ligands in
D
enantioselective alkylation. In this paper, we report the enantiose-
lective alkylation of aldehydes using dialkylzincs catalyzed by diols
derived from monosaccharides.
Scheme 1. Preparation of diol by cleavage of benzylidene acetal.
* Corresponding author. E-mail address: mhayashi@kobe-u.ac.jp (M. Hayashi).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.090

4222
K. Michigami, M. Hayashi / Tetrahedron 69 (2013) 4221e4225
Table 1
dialkylzinc was added to a solution of diol in hexane. This obser-
vation indicated the formation of alkoxide that will act as a chiral
Lewis acid in the reaction. We will propose one of the possible
paths in the asymmetric reaction with diethylzinc in Scheme 2.
Diethylzinc may be efficiently trapped at 3-methoxy and 4-hydroxy
moieties and activated leading to the increase of nucleophilicity of
ethyl group. Aldehydes will be attacked from Si-face by activated
diethylzinc to afford (S)-product.
Enantioselective ethylation of benzaldehyde catalyzed by chiral diols derived from
monosaccharides
Scheme 2. Possible mechanism of asymmetric ethylation.
In conclusion, we have revealed that simple chiral diols
derived from monosaccharides, such as
a-D-glucose, a-D-mannose,
and -galactose can serve as ligands in enantioselective alkyl-
a-D
ations using dialkylzincs. Although the obtained enantioselectiv-
ities were not satisfactory and high catalysts loading were
necessary, this is the first example of the use of simple chiral diols
lower temperature (ꢀ20 ꢁC) was necessary to provide the product
in high ee. Other diols provided the product in moderate ee
(26e75% ee). It should be noted that these chiral diols 3e5 can be
separated easily by extraction.
After we confirmed that the chiral diols 3 and 5 served as
effective catalysts, we then examined a variety of aldehydes
derived from monosaccharides. Monosaccharides, such as
D-glu-
cose, -mannose, and -galactose exist widely in nature. Therefore,
D
D
monosaccharides with amino acids as chiral sources are attractive
molecules. We are currently investigating the use of these simple
diols as catalysts in other asymmetric reactions.
including a,b-unsaturated and aliphatic aldehydes. Table 2 shows
that enantioselective alkylation proceeded to give the alkylated
products in moderate to high ee.
3. Experimental
3.1. General
Table 2
Enantioselective alkylation of aldehydes catalyzed by diol 3 or 5a
All reactions were carried out in well cleaned and oven-dried
glassware with magnetic stirring. Operations were performed un-
der an atmosphere of dry argon using Schlenk and vacuum tech-
niques. All starting materials were obtained from commercial
sources and used without further purification unless otherwise
stated. Melting points were measured by Yanaco MP-500D and were
not corrected. 1H and 13C NMR spectra (400 and 100.6 MHz, re-
spectively) were recorded on a JEOL JNM-LA 400 instrument using
Me4Si as an internal standard (0 ppm). The following abbreviations
are used in connection with NMR; s¼singlet, d¼doublet, t¼triplet,
q¼quartet and m¼multiplet. Mass spectra were measured using
Thermo Quest LCQ DECA plus. IR spectra were measured with
a Thermo SCIENTIFIC NICOLET iS 5. Elemental analyses were carried
out using Yanako CHN recorder MT-5. High resolution mass spectra
(HRMS) were measured by JEOL JMS-T100LP AccuTOF LC-Plus (ESI).
Thin layer chromatography (TLC) was carried out on Merk 25 TLC
aluminum sheets silica gel 60 F254. HPLC analyses were carried out in
a HITACHI L-2000 series instrument equipped with diode array
detector using chiral columns CHIRALPAK AD-H or CHIRALCEL
OD-H. GC analyses were performed in a HITACHI G-5000 series in-
Entry
R1
R2
Catalyst
Yield/%b
ee/%c
1
2
3
4
5
6
7
8
Ph
Ph
Et
Et
Et
Et
Et
Et
Et
Et
3
5
3
5
3
5
5
5
5
5
3
79
63
67
67
39
48
44
53
44
21
42
81 (S)
84 (S)
67 (S)
60 (S)
64 (S)
47 (S)
35 (S)
53 (S)
39 (S)
48 (S)
53 (R)
4-ClC6H4
4-MeC6H4
4-MeOC6H4
(E)-PhCH]CH
PhCH2CH2
2-Furyl
2-Thienyl
c-C6H11
Ph
9
Et
Et
n-Bu
10
11d
a
All reactions were carried out using 5 equiv of dialkylzincs.
Isolated yield.
Determined by chiral HPLC or GC column. See Supplementary data.
Reaction was carried out at 0 ꢁC using heptane as a solvent.
b
c
d
strument equipped with a FID detector and a capillary column, a-
DEX-325 or
b
-DEX-225 (SUPELCOÒ, 30 mꢂ0.25 mm i.d., 0.25
mm
Dimethylzinc showed low reactivity and selectivity at 0 ꢁC (9%,
13% ee, respectively). Although the ees of the products of this re-
action did not parallel those of -amino alcohol catalyzed reactions,
film). Optical rotations were measured on a HORIBA SEPA-300 Po-
larimeter for solution in a 1 dm cell. Diethylzinc and dimethylzinc
were kindly donated by Tosoh Finechem Co.
b
this is the first report using simple chiral diols derived from
monosaccharides in catalytic asymmetric reactions.
Unlike enantioselective alkylation catalyzed by
b-amino alco-
3.2. General procedure of preparation of 4,6-diol catalysts
hols, explanation of mechanism is not easy because of the existence
of many chiral centers in monosaccharides and of inversion of
enantioselectivity occurred by changes in protecting groups and
anomeric chemistry. We observed evolution of ethane when
A mixture of methyl 4,6-benzylidene-2,3-O-protected-D-gluco-
pyranoside (3 mmol), methanol (10 mL), and 1 M HCl in methanol
(5 mL) was stirred for 5 h at room temperature. K2CO3 (100 mg) was

K. Michigami, M. Hayashi / Tetrahedron 69 (2013) 4221e4225
4223
then added and the reaction mixture was stirred for 1 min. After
filtration through Celite, the filtrate was passed through DOWEXÔ
50Wꢂ2 50e100 mesh (H) cation exchange resin and evaporated.
The residue was purified by silica gel column chromatography
[eluent: hexane/ethyl acetate (1/1) then ethyl acetate] to give
604, 755, 918, 1029, 1223, 1370, 1742, 2932, 3000e3500 (br) cmꢀ1; 1H
NMR (400 MHz, CDCl3) 1.68 (br s, 1H, OH), 2.10 (s, 3H, CH3COO), 2.11
d
(s, 3H, CH3COO), 2.94 (br s, 1H, OH), 3.41 (s, 3H, OMe), 3.7e3.8 (m, 2H,
H4; H6), 3.8e3.9 (m, 2H, H5; H60), 4.84 (dd, J¼10.3, 3.3 Hz, 2H, H2),
4.91 (d, J¼3.3 Hz, 1H, H1), 5.2e5.3 (m, 1H, H3); 13C NMR (100.6 MHz,
methyl 2,3-O-protected-
D
-glucopyranoside.
CDCl3): d 20.8, 20.9, 55.3, 62.0, 69.9, 70.7, 71.1, 73.4, 96.8, 170.3, 172.0;
HRMS [ESI]. m/z calcd for C11H18O8Na: 301.0899 [MþNa]þ, found:
301.0899 [MþNa]þ; Anal. Calcd for C11H18O8: C, 47.48; H, 6.52. Found:
C, 47.48; H, 6.52.
3.2.1. Methyl 2,3-di-O-benzyl-a-D-glucopyranoside (1). White solids;
mp 73e75 ꢁC, (lit.10 mp 73e75 ꢁC); ½a 2D4
ꢃ
þ19.3 (c 1.0, CHCl3) (lit.10
½ ꢃ
a 2D4
þ18.1 (c 1.0, CHCl3)); IR (KBr) 696, 735, 754, 1000, 1023, 1044, 1057,
1119, 3200e3600 (br) cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
1.97 (br s, 1H,
3.2.7. Methyl 2,3-di-O-benzoyl-a-D-glucopyranoside (7). White solids;
OH), 2.33 (br s, 1H, OH), 3.39 (s, 1H, OMe), 3.4e3.6 (m, 2H, H2; H4),
3.6e3.7 (m, 1H, H5), 3.7e3.8 (m, 3H, H3; H6; H60), 4.66 (d, J¼3.2 Hz,
1H, OCH2Ph), 4.70 (d, J¼12.0 Hz, 1H, OCH2Ph), 4.74 (d, J¼12.0 Hz, 1H,
OCH2Ph), 5.03 (d, J¼3.2 Hz, 1H, H1), 7.3e7.4 (m, 10H, PhH); 13C NMR
mp 63e65 ꢁC; ½a 2D9
ꢃ
þ178.2 (c 1.0, CHCl3) (lit.14
½
a 1D9
ꢃ
þ165.6 (c 1.0,
CHCl3)); IR (KBr) 696, 739, 961, 1028, 1045, 1094, 1194, 1275, 1354,
1
1453, 1722, 2928, 3000e3500 (br) cmꢀ1; H NMR (400 MHz, CDCl3)
d
1.72 (br s, 1H, OH), 2.16 (br s, 1H, OH), 3.43 (s, 3H, OMe), 3.86 (ddd,
(100.6 MHz, CDCl3):
d
55.2, 62.4, 70.3, 70.6, 73.1, 75.4, 76.7, 79.7, 81.2,
J¼6.7, 6.7, 3.1 Hz, 1H, H5), 3.9e4.0 (m, 3H, H4; H6; H60), 5.12 (d,
J¼3.9 Hz, 1H, H1), 5.23 (dd, J¼3.9, 9.5 Hz, 1H, H2), 5.74 (dd, J¼10.3,
9.5 Hz, 1H, H3), 7.3e7.4 (m, 4H, PhH), 7.5e7.6 (m, 2H, PhH), 7.9e8.0 (m,
98.1, 127.9, 128.0, 128.1, 128.5, 128.6, 137.9, 138.6; HRMS [ESI]. m/z calcd
for C21H25O6: 373.1651 [MꢀH]ꢀ, found: 373.1644 [MꢀH]ꢀ; Anal. Calcd
for C21H26O6: C, 67.36; H, 7.00. Found: C, 66.99; H, 6.83.
4H, PhH); 13C NMR (100.6 MHz, CDCl3):
d 55.4, 62.1, 69.6, 71.3, 71.5,
74.3, 97.1,128.4,129.08,129.15,129.87,129.88,133.3,133.5,166.0,167.5;
HRMS [ESI]. m/z calcd for C21H21O8: 401.1236 [MꢀH]ꢀ, found:
401.1237 [MꢀH]ꢀ.
3.2.2. Methyl 2,3-di-O-benzyl-b-D-glucopyranoside (2). White solids;
a 30
ꢁ
mp 113 C; ½ ꢃD þ19.0 (c 0.5, CHCl3); IR (KBr) 560, 648, 696, 721, 732,
993, 1029, 1062, 1093, 1118, 3100e3500 (br) cmꢀ1; 1H NMR (400 MHz,
CDCl3)
d
2.04 (br s, 1H, OH), 2.28 (br s, 1H, OH), 3.3e3.4 (m, 1H, H5),
3.2.8. Methyl 2,3-di-O-benzyl-
a
-
-galactopyranoside (8). Colorless oil;
þ46.9 (c 0.67, CHCl3) (lit.15
½
aDꢃ2D9 þ43 (c 0.67, CHCl3)); IR (KBr) 686,
3.41 (dd, J¼8.6, 7.8 Hz, 1H, H2), 3.45 (dd, J¼9.0, 8.6 Hz, 1H, H3), 3.58 (s,
1H, OMe), 3.77 (dd, J¼11.9, 5.0 Hz, 1H, H6), 3.89 (dd, J¼11.9, 3.2 Hz, 1H,
H60), 4.37 (d, J¼7.6 Hz, 1H, H1), 4.67 (d, J¼11.6 Hz, 1H, PhCH2), 4.71 (d,
J¼11.2 Hz, 1H, PhCH2), 4.93 (d, J¼11.2 Hz, 1H, PhCH2), 4.97 (d,
J¼11.6 Hz, 1H, PhCH2), 7.2e7.4 (m, 10H, PhH); 13C NMR (100.6 MHz,
½
a 2D9
ꢃ
706, 991, 1025, 1068, 1094, 1275, 1451, 1720, 2933, 3000e3500 br
cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 2.46 (br s, 1H, OH), 2.78 (br s, 1H,
OH), 3.37 (s, 3H, OMe), 3.7e3.9 (m, 5H, H2; H3; H5; H6; H60), 4.0e4.1
(m, 1H, H4), 4.67 (d,1H, PhCH2), 4.69 (d, J¼11.9 Hz, 1H, PhCH2), 4.70 (d,
J¼3.2 Hz, 1H, H1), 4.81 (d, J¼11.9 Hz, 2H, PhCH2), 7.3e7.4 (m, 10H,
CDCl3): d 57.3, 62.7, 70.5, 74.6, 74.8, 75.2, 82.0, 83.8, 105.0, 127.7, 127.9,
128.0, 128.1, 128.4, 128.6, 138.3, 138.5; HRMS [ESI]. m/z calcd for
C21H25O6: 373.1651 [MꢀH]ꢀ, found: 373.1657 [MꢀH]ꢀ; Anal. Calcd for
C21H26O6: C, 67.36; H, 7.00. Found: C, 67.43; H, 7.17.
PhH); 13C NMR (100.6 MHz, CDCl3):
d 55.3, 63.0, 68.8, 69.1, 72.9, 73.5,
75.6, 98.6,127.8,127.9,128.0,128.4,128.5,138.0,138.2; HRMS [ESI]. m/z
calcd for C21H25O6: 373.1651 [MꢀH]ꢀ, found: 373.1650 [MꢀH]ꢀ.
3.2.3. Methyl 2,3-di-O-methyl-
a
-
D
-glucopyranoside (3). White solids;
3.3. General procedure for asymmetric alkylation using
diethylzinc
mp 78e80 ꢁC (lit.11 83e85 ꢁC); White solids; ½a 2D7
þ151.5 (c 1.0, CHCl3)
ꢃ
(lit.11
½
a 2D3
ꢃ
þ151.5 (c 1.0, CHCl3)); IR (KBr) 567, 628, 705, 745, 853, 904,
960, 894, 1025, 1050, 1073, 1104, 1134, 3100e3600 (br) cmꢀ1; 1H NMR
(400 MHz, CDCl3) 2.07 (br s, 1H, OH), 2.18 (br s, 1H, OH), 3.23 (dd,
To a mixture of catalyst (0.2 mmol) and solvent (0.75 mL) was
added diethylzinc (5.0 mmol) slowly at ꢀ20 ꢁC and stirred for
30 min at 0 ꢁC. After that, aldehyde (1.0 mmol) in solvent (0.25 mL)
was added at ꢀ40 ꢁC and stirred for 48 h at ꢀ20 ꢁC. The reaction
was quenched by addition of 1 N HCl aq and extracted with diethyl
ether. The combined organic layers were dried over Na2SO4, and
evaporated. The residue was purified by silica gel column chro-
matography (eluent: hexane/ethyl acetate¼3/1).
d
J¼9.2, 3.2 Hz, 1H, H2), 3.4e3.6 (m, 8H, OMe ꢂ2; H3; H4), 3.6e3.7 (m,
4H, OMe; H5), 3.81 (dd, J¼11.6, 4.0 Hz, 1H, H6), 3.87 (dd, J¼11.6, 4.0 Hz,
1H, H60), 4.86 (d, J¼3.2 Hz, 1H, H1), 13C NMR (100.6 MHz, CDCl3):
d
55.3, 55.5, 61.3, 62.4, 76.7, 81.9, 82.7, 97.5, HRMS [ESI]. m/z calcd for
C9H17O6: 221.1025 [MꢀH]ꢀ, found: 221.1025 [MꢀH]ꢀ.
3.2.4. Methyl 2,3-di-O-methyl-b-D-glucopyranoside (4). White solids;
mp 42 ꢁC (lit.12 mp 62e64 ꢁC); ½a 3D2
ꢃ
ꢀ41.3 (c 1.0, CHCl3) (lit.12
3.3.1. (S)-1-Phenylpropanol. ½a D27
ꢃ
ꢀ34.3 (c 1.00, CHCl3) (lit.16
½ ꢃ
a 2D9
[a
]Dꢀ47.8 (c 1.0, CHCl3)); IR (KBr) 614, 890, 955, 996, 1025, 1061,
þ41.9 (c 1.00, CHCl3, 96% ee (R))). The ee of the product was de-
termined as 84% ee (S) by HPLC analysis. tR of R-isomer, 15.1 min; tR of
S-isomer, 17.6 min [column, CHIRALCEL OD-H (DAICEL): eluent,
hexanee2-propanol (99:1), 1.0 mL/min]; 1H NMR (400 MHz, CDCl3):
1085, 1103, 3000e3700 (br) cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 2.28
(br s, 1H, OH), 2.89 (br s, 1H, OH), 3.00 (dd, J¼9.2, 7.8 Hz, 1H, H2), 3.14
(dd, J¼9.1, 9.0 Hz, 1H, H4), 3.3e3.4 (m, 1H, H5), 3.51 (dd, J¼9.2, 9.1 Hz,
1H, H3), 3.56 (s, 3H, OMe), 3.58 (s, 3H, OMe), 3.64 (s, 3H, OMe), 3.7e4.0
(m, 2H, H6; H60), 4.25 (d, J¼7.8 Hz, 1H, H1), 13C NMR (100.6 MHz,
d
0.92 (t, J¼7.2 Hz, 3H, CH2CH3), 1.7e1.8 (m, 2H, CH2CH3), 4.61 (t,
J¼7.2 Hz, 1H, PhCH), 7.3e7.4 (m, 5H, PhH).
CDCl3): d 57.2, 60.2, 60.9, 62.5, 70.1, 74.7, 83.6, 95.6, 104.6, HRMS [ESI].
m/z calcd for C9H17O6: 221.1025 [MꢀH]ꢀ, found: 221.1025 [MꢀH]ꢀ.
3.3.2. (S)-1-(4-Chlorophenyl)-1-propanol. ½a D31
ꢀ15.1 (c 1.00, benzene)
ꢃ
(lit.16
½
a 2D9
ꢃ
þ24.1 (c 1.00, benzene, 90% ee (R))). The ee of the product
3.2.5. Methyl 2,3-di-O-methyl-
a
-
D
-mannopyranoside (5). White solids;
þ40.7 (c 1.0, CHCl3); IR (KBr) 614, 890, 955, 996, 1025,
2.13 (br s, 1H,
was determined as 67% ee (S) by HPLC analysis. tR of S-isomer,
12.2 min; tR of R-isomer, 13.0 min [column, CHIRALCEL OD-H (DAI-
CEL): eluent, hexanee2-propanol (95:5), 0.5 mL/min]; 1H NMR
mp 49 ꢁC; ½a 2D6
ꢃ
1061, 3000e3700 br cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
OH), 2.50 (br s, 1H, OH), 3.3e3.7 (m, 12H, OMe ꢂ3; H2; H4; H5),
(400 MHz, CDCl3):
CH2CH3), 3.75 (s, 1H, OH), 4.61 (t, J¼6.4 Hz, 1H, ArCH), 7.2e7.4 (m, 4H,
ArH).
d
0.91 (t, J¼7.2 Hz, 3H, CH2CH3), 1.6e1.9 (m, 2H,
3.8e3.9 (m, 3H, H3; H6; H60), 4.82 (s, 1H, H1), 13C NMR (100.6 MHz,
CDCl3): d 54.9, 57.1, 59.1, 62.7, 67.1, 72.0, 75.8, 81.0, 98.5; HRMS [ESI]. m/
z calcd for C9H17O6: 221.1025 [MꢀH]ꢀ, found: 221.1025 [MꢀH]ꢀ.
3.3.3. (S)-1-(4-Methylphenyl)-1-propanol. ½a D31
ꢀ20.2 (c 0.77, ben-
ꢃ
3.2.6. Methyl 2,3-di-O-acetyl-
a
-
D
-glucopyranoside (6). Colorless oil;
zene) (lit.17
½
a 2D0
ꢃ
ꢀ38.5 (c 1.10, benzene, 90% ee (S))). The ee of the
½
a 2D9
ꢃ
þ149.2 (c 0.46, CHCl3) (lit.13
½
a 1D9
ꢃ
þ127 (c 0.46, CHCl3)); IR (KBr)
product was determined as 60% ee (S) by HPLC analysis. tR of R-isomer,

4224
K. Michigami, M. Hayashi / Tetrahedron 69 (2013) 4221e4225
16.7 min; tR of S-isomer, 19.2 min [column, CHIRALPAK AD-H (DAI-
CEL): eluent, hexanee2-propanol (99:1), 1.0 mL/min]; 1H NMR
by silica gel column chromatography (eluent: hexane/ethyl
acetate¼9/1 then 4/1).
(400 MHz, CDCl3):
d
0.91 (t, J¼7.6 Hz, 3H, CH2CH3), 1.6e1.9 (m, 2H,
CH2CH3), 2.35 (s, 3H, Me), 4.57 (t, J¼6.6 Hz, 2H, ArCH), 7.16 (d, J¼8.4 Hz,
3.4.1. (R)-1-Phenyl-1-pentanol. ½a D28
ꢃ
þ19.8 (c 1.20, CHCl3) (lit.16
½ ꢃ
a 2D9
2H, ArH), 7.24 (d, J¼8.4 Hz, 1H, ArH).
þ40.0 (c 1.00, CHCl3, 98% ee (R))). The ee of the product was de-
termined as 54% ee (R) by GC analysis. tR of R-isomer, 24.8 min; tR of S-
3.3.4. (S)-1-(4-Methoxyphenyl)-1-propanol. ½a D27
ꢃ
ꢀ21.8 (c 1.20, ben-
isomer, 25.6 min [column, SUPELCO
1H NMR (400 MHz, CDCl3):
a
-DEXÔ 325: 120 ꢁC (constant)];
zene) (lit.16
½
a 2D9
ꢃ
þ41.9 (c 1.00, benzene, 80% ee (R))). The ee of the
d
0.88 (t, J¼7.0 Hz, 3H, CH2CH3),1.3e1.4 (m,
product was determined as 64% ee (S) by GC analysis. tR of R-isomer,
67.5 min; tR of S-isomer, 70.9 min [column, SUPELCO -DEXÔ 225:
120 ꢁC (constant)]; 1H NMR (400 MHz, CDCl3):
0.90 (t, J¼7.6 Hz, 3H,
4H, CH(OH)CH2C2H4CH3), 1.6e1.9 (m, 2H, CH(OH)CH2Pr), 4.67 (t,
J¼6.6 Hz, 1H, CH(OH)Bu), 7.3e7.4 (m, 5H, ArH).
b
d
CH2CH3), 1.6e1.9 (m, 2H, CH2CH3), 3.73 (s, 1H, OH), 3.82 (s, 3H, OMe),
4.54 (t, J¼7.0 Hz, 1H, ArCH), 6.83 (d, J¼8.4 Hz, 2H, ArH), 7.27 (d,
J¼8.4 Hz, 2H, ArH).
3.4.2. (S)-1-Phenylethanol. ½a D27
ꢃ
ꢀ5.8 (c 0.62, CHCl3) (lit.18
½ ꢃ
a 2D3
þ55.9 (c 0.78, CHCl3, 94.9% ee (R))). The ee of the product was de-
termined as 13% ee (S) by GC analysis. tR of S-isomer, 13.1 min; tR of R-
isomer, 13.6 min [column, Spelco
NMR (400 MHz, CDCl3):
a
-DEXÔ 325: 110 ꢁC (constant)]; 1H
3.3.5. (S,E)-1-Phenylpent-1-en-3-ol. ½a D30
ꢃ
ꢀ8.6 (c 1.00, CHCl3) (lit.16
d
1.51 (d, J¼6.8 Hz, 3H, CH(OH)CH3); 4.91
½
a 2D8
ꢃ
þ6.1 (c 1.01, CHCl3, 75% ee (R))). The ee of the product was de-
(q, J¼6.8 Hz, 1H, PhCH(OH)Me); 7.2e7.4 (m, 5H, ArH).
termined as 47% ee (S) by HPLC analysis. tR of R-isomer, 11.0 min; tR of
S-isomer, 18.5 min [column, CHIRALCEL OD-H (DAICEL): eluent,
hexanee2-propanol (95:5), 1.0 mL/min]; H NMR (400 MHz, CDCl3):
Acknowledgements
1
d
0.98 (t, J¼7.6 Hz, 3H, CH2CH3), 1.5e1.9 (m, 2H, CH2CH3), 3.75 (s,
This work was supported by a Grant-in-Aid (No. B23350043) for
Scientific Research on Innovative Areas ‘Molecular Activation Di-
rected toward Straightforward Synthesis’, Ministry of Education,
Culture, Sports, Science and Technology (MEXT), Japan and by
Special Coordination Funds for Promoting Science and Technology,
Creation of Innovation Centers for Advanced Interdisciplinary Re-
search Areas (Innovative Bioproduction Kobe), MEXT, Japan.
3H, OH), 4.1e4.2 (m, 1H, PhC2H2CHOH), 6.22 (d, J¼16.0, 3.0 Hz, 1H,
PhCH]CH), 6.58 (d, J¼16.0 Hz, 1H, PhCH]CH), 7.1e7.5 (m, 5H, PhH).
3.3.6. (S)-1-Phenyl-3-pentanol. ½a D29
ꢃ
þ4.8 (c 1.00, EtOH) (lit.16
½ ꢃ
a 2D8
ꢀ23.4 (c 1.00, EtOH, 81% ee (R))). The ee of the product was de-
termined as 35% ee (S) by HPLC analysis. tR of R-isomer, 8.2 min; tR of S-
isomer, 11.6 min [column, CHIRALPAK AD-H (DAICEL): eluent,
1
hexanee2-propanol (99:1), 1.0 mL/min]; H NMR (400 MHz, CDCl3):
Supplementary data
d
0.95 (t, J¼7.6 Hz, 3H, CH2CH3), 1.5e1.9 (m, 4H, PhCH2CH2CH(OH)
CH2CH3), 2.6e9.9 (m, 2H, PhCH2), 3.5e3.6 (m, 1H, CHOH), 7.1e7.3 (m,
5H, ArH).
Detailed experimental procedures and characterization data
(1H, 13C, IR, mass spectrometry) can be found. Supplementary data
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.03.090.
3.3.7. (S)-1-(2-Furyl)-1-propanol. ½a D30
ꢃ
ꢀ13.3 (c 1.00, CHCl3) (lit.16
½ ꢃ
a 2D8
þ25.9 (c2.10, CHCl3, 90% ee (R))). The ee of the product was determined
as 53% ee (S) by GC analysis. tR of R-isomer, 19.3 min; tR of S-isomer,
References and notes
20.4 min [column, SUPELCO
(400 MHz, CDCl3):
b
-DEXÔ 225: 90 ꢁC (constant)]; 1H NMR
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(dd, J¼3.2, 1.2 Hz, 1H, ArH), 7.38 (d, J¼1.2 Hz, 1H, ArH).
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-DEXÔ 225: 120 ꢁC (con-
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½ ꢃ
a 2D8
þ4.5 (c 1.00, CHCl3, 67% ee (R))). The ee of the product was determined
as 48% ee (S) by GC analysis. tR of S-isomer, 21.2 min; tR of R-isomer,
22.8 min [column, SUPELCO b
-DEXÔ 225: 100 ꢁC (constant)]; 1H NMR
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Riera, A.; Verdaguer, X. Tetrahedron: Asymmetry 2004, 15, 2085e2090; (q) Sza-
(400 MHz, CDCl3): 0.9e1.9 (m, 16H, C6H11CH(OH)CH2CH3), 4.2e4.3
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