Enantioselective diethylzinc addition to aldehydes catalyzed by Ti(IV) complex of unsymmetrical chiral bis(sulfonamide) ligands of trans-cyclohexane 1,2-diamine

Article abstract of DOI:10.1016/j.tet.2006.11.022

Titanium(IV) complexes of bidentate trans-cyclohexane 1,2-diamine-based unsymmetrical chiral bis(sulfonamide) ligands were evaluated as catalysts for the asymmetric addition of diethylzinc to aldehydes. The reaction provided secondary alcohols in quantita

Full text of DOI:10.1016/j.tet.2006.11.022

Tetrahedron 63 (2007) 598–601
Enantioselective diethylzinc addition to aldehydes catalyzed
by Ti(IV) complex of unsymmetrical chiral bis(sulfonamide)
ligands of trans-cyclohexane 1,2-diamine
*
Alakesh Bisai, Pradeep K. Singh and Vinod K. Singh
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, U.P., India
Received 3 September 2006; revised 20 October 2006; accepted 9 November 2006
Available online 27 November 2006
Abstract—Titanium(IV) complexes of bidentate trans-cyclohexane 1,2-diamine-based unsymmetrical chiral bis(sulfonamide) ligands were
evaluated as catalysts for the asymmetric addition of diethylzinc to aldehydes. The reaction provided secondary alcohols in quantitative yields
and very good enantioselectivity (up to 96% ee).
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
through the desymmetrization of cyclohexyl-N-tosyl aziri-
dines with chiral amines (Fig. 1).
7
The enantioselective addition of organozinc reagents to
carbonyl compounds catalyzed by a metal–chiral ligand
complex has attracted attention for a long time. Since the
NHSO R
NHTs
2
1
reaction is very useful for the synthesis of optically active
secondary alcohols, several excellent chiral ligands have
been evaluated for dialkylzinc addition to carbonyls. In
catalytic asymmetric systems, small changes in the donating
ability of a ligand or the size of a substituent can have a
dramatic effect on the catalytic efficiency and enantioselec-
tivity. Thus, there is a need for developing new types of
NHSO2R
NHSO2Mes
2
1
R = p-Tol, 1a
NHTs
NHSO R
3
3
3
a, R = C H ;
6 5
2
b, R = o-NO2C6H4;
c, R = p-NO C H ;
2
6
4
3d, R = CH ; 3e, R = CF ;
3
3
2
3f, R = p-MeOC H ;
3
6 4
3
g, R = 3,5-Cl2-2-OHC6H2;
h, R = p-BrC H .
3
6
4
chiral ligands. Cyclohexanediamine based C -symmetric
2
bis(sulfonamide) chiral ligands of type 1, which bind well
with early transition metals and main group elements, have
been used for enantioselective addition of organozinc to
Figure 1. Symmetrical and unsymmetrical chiral ligands based on trans-
,2-cyclohexane diamine.
1
3
–5
carbonyl compounds.
In this paper, we report that these unsymmetrical
bis(sulfonamide) ligands are as efficient as C -symmetric
2
The use of C -symmetric ligands has an advantage of re-
2
bis(sulfonamide) ligands in the enantioselective addition of
diethylzinc to aldehydes.
stricting the number of possible competing diastereomeric
transition states. To the best of our knowledge, there is
6
only one report disclosed by Walsh and co-workers where
application of a pseudo C -symmetric bis(sulfonamide) li-
2
2
. Results and discussion
gand 2 has been reported for the enantioselective diethylzinc
addition to benzaldehyde. However, the enantiomeric ex-
5
c
At the outset, the addition of diethylzinc to benzaldehyde
was studied in the presence of 2–20 mol % catalyst prepared
cess was 91% using ligand 2, which is lower than the ee
obtained from C -symmetric ligand 1a (97% ee).
i
ꢁ
2
from a chiral ligand 3a and Ti(O Pr) at ꢀ30 C (Table 1).
4
The reaction completed in 6 h and the product was obtained
in very good yields (81–87%) and high enantioselectivities
Recently, we developed a very good method for the synthe-
sis of unsymmetrical bis(sulfonamide) ligands of type 3
(
88–96% ee). It is obvious from the results that 4–6 mol %
catalyst is optimum for high asymmetric induction (96%
ee) in the reaction. Under these optimized conditions, other
chiral ligands 3b–3h were evaluated for the same reaction
*
Corresponding author. Tel.: +91 512 2597291; fax: +91 512 2597436;
e-mail: vinodks@iitk.ac.in
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.022

A. Bisai et al. / Tetrahedron 63 (2007) 598–601
Table 1. Enantioselective diethylzinc addition to benzaldehyde in the pres-
ence of different chiral ligands 3a–3h
599
3. Conclusion
i
3
-Ti(OPr) , toluene,
30 °C, 6 h
OH
In conclusion, the chiral Ti(IV)–3 complex prepared from
Ti(O Pr) and unsymmetric bis(sulfonamide) ligands 3 was
4
i
-
4
PhCHO
+
Et Zn
2
Ph
found to be an effective catalyst for the enantioselective di-
ethylzinc addition to aldehydes. The reaction can furnish
a variety of secondary alcohols in good to excellent yields
(up to 99%) with excellent enantioselectivities (up to 96%
ee). These results provide a new way to design and synthe-
size new chiral ligands for enantioselective reactions.
a
b
Entry
Ligand
Mol %
% Yield
% ee
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
2
4
6
10
20
4
4
4
4
4
83
87
81
83
82
82
81
75
82
85
53
88
94
96
96
93
88
88
94
94
93
81
76
91
4. Experimental
4.1. General
1
1
1
0
1
2
3g
3h
4
4
All the chemicals were purchased either from Aldrich or
Alfa–Aesar and used without further purification. H and
C NMR spectra were recorded on JEOL JNM-LA 400
1
a
Isolated yields after purification.
The ees were determined by HPLC using chiralcel OD-H column.
1
3
b
spectrometer. All chemical shifts are quoted on the d scale,
with TMS as internal standard, and coupling constants are re-
ported in hertz. Routine monitoring of reactions was per-
formed by TLC using 0.2 mm Kieselgel 60 F254 precoated
aluminum sheets, commercially available from Merck. Visu-
alization was done by fluorescence quenching at 254 nm or
by exposure to iodine vapor. All the column chromatographic
separations were done by using silica gel (Acme’s, 100–200
mesh). HPLC was done on Daicel chiral column having
and the results are summarized in Table 1. The ligand 3a
(
reaction. The ligands 3c, 3d, and 3e showed comparable
asymmetric inductions (93–94% ee). Tridentate ligand 3g
having a hydroxyl group on the phenyl ring gave only
R¼Ph) gave the highest enantioselectivity (96% ee) in the
7
6% ee in the reaction.
The ligands 3a and 3d were selected for evaluation on other
substrates. Most of the aromatic aldehydes gave high asym-
metric induction in the diethylzinc addition reaction (Table
0
.46 cm I.D.ꢂ25 cm L. Petroleum ether used was of boiling
ꢁ
range 60–80 C. Reactions that needed anhydrous conditions
were run under the atmosphere of nitrogen using flame-dried
glassware. The organic extracts were dried over anhydrous
sodium sulfate. Evaporations of solvents were performed at
reduced pressure. Toluene and diethyl ether were both dis-
tilled from sodium benzophenone-ketyl. Dichloromethane
was distilled from calcium hydride. Acetonitrile was distilled
from anhydrous phosphorus pentoxide under nitrogen.
2
). However, 3a gave better results than 3d in the addition
of diethylzinc to cyclohexyl carboxaldehyde (Table 2, entry
2). The reactions were carried out on other aliphatic alde-
1
hydes, but we could not determine ee due to lack of base
line separation of products on chiral columns we had in
our laboratory. The mechanism of the reaction can be ex-
plained based on the literature work with C -symmetric
2
5
ligands.
4.1.1. 4-Methyl-N-(2-trifluoromethanesulfonylamino-
cyclohexyl)-benzene sulfonamide. This was prepared as per
7b
Table 2. Enantioselective diethylzinc addition to aldehydes in the presence
of different chiral ligands 3a and 3d
the general procedure from N-tosyl cyclohexyl aziridines;
ꢁ
25
7
0% yield (0.516 g); white solid; mp 123–126 C; [a]D
i
3
a and 3d-Ti(O Pr)4,
ꢀ34.0 (c 1.0, CHCl ); R 0.36 (30% EtOAc in petroleum
OH
3
f
1
toluene, -30 °C, 6 h
ether); H NMR (CDCl , 400 MHz) d: 7.77 (d, J¼8.3 Hz,
3
RCHO
+
Et2Zn
R
2
H), 7.33 (d, J¼8.3 Hz, 2H), 5.97 (d, J¼7.1 Hz, 1H, NH),
4.97 (d, J¼8.8 Hz, 1H, NH), 3.16–3.25 (m, 1H), 2.92–3.00
a
b
Entry
R
% Yield
% ee
(m, 1H), 2.44 (s, 3H), 2.17–2.23 (m, 1H), 1.42–1.71 (m,
13
3
a
3d
3a
3d
3H), 1.08–1.39 (m, 4H); C NMR (CDCl , 100 MHz) d:
3
143.9, 137.3, 129.9, 126.9, 59.3, 56.4, 33.9, 33.0, 24.5, 24.2,
21.6. Anal. Calcd for C H F N O S : C, 41.99; H, 4.78;
N, 7.00. Found: C, 42.19; H, 4.83; N, 7.02.
1
2
3
4
5
6
7
8
9
Ph
87
97
81
92
98
94
84
91
74
83
85
56
75
98
84
84
99
93
74
94
74
87
94
57
96
96
82
95
93
92
92
93
76
93
95
96
94
96
79
93
90
94
92
93
83
92
95
82
4-Cl–C
4-OMe–C
6 4
3-Br–C H
6 4
H
14 19 3 2 4 2
6
H
4
i
4- Pr–C
3-Cl–C
3-F–C
3-Cl-4-F–C
2,3-F –C
3,5-Me –C
3-Me–C
6 4
H
H
6 4
H
6 4
4.1.2. N-(2-p-Toluenesulfonylamino-cyclohexyl)-3,5-
dichloro-2-hydroxy-benzene sulfonamide. This was
prepared as per the general procedure from N-tosyl cyclo-
7
b
6
H
3
2
6 3
H
hexyl aziridines; 66% yield (0.554 g); light yellow solid; mp
1
1
1
0
1
2
2
6
H
3
ꢁ
1–84 C; [a]D +3.70 (c 1.0, CHCl ); R 0.42 (50% EtOAc
3 f
25
8
6 4
H
1
c
in petroleum ether); H NMR (CDCl , 400 MHz) d: 7.65–
3
c-C
6
H
11
7
.78 (m, 3H), 7.55 (s, 1H), 7.30 (d, J¼7.8 Hz, 2H), 5.87
a
Isolated yields were reported here after purification.
The ees were determined by HPLC using chiralcel OD-H or chiralpak
AD-H column.
Reaction time was 10–12 h and ees were determined using its 4-methoxy-
benzoate.
(br s, 1H, NH), 4.55 (br s, 1H, NH), 2.75–2.95 (m, 2H),
b
2
1
.43 (s, 3H), 2.03–2.15 (m, 1H), 1.50–1.70 (m, 3H), 1.09–
.24 (m, 4H). Anal. Calcd for C H Cl N O S : C, 46.25;
c
19 22
2 2 5 2
H, 4.49; N, 5.68. Found: C, 46.39; H, 4.51; N, 5.71.

600
A. Bisai et al. / Tetrahedron 63 (2007) 598–601
ꢀ
1
1
4.2. General procedure for the enantioselective diethyl-
zinc addition to aldehydes
973, 832 cm
;
H NMR (CDCl , 400 MHz) d: 7.25
3
(d, J¼8.0 Hz, 2H), 7.20 (d, J¼8.0 Hz, 2H), 4.54 (t, J¼
6
.6 Hz, 1H), 2.90 (h, J¼7.1 Hz, 1H), 1.92 (br s, 1H, OH),
Diethylzinc (1.2 mL, 1 M solution in n-hexane) was added
to a solution of ligand 3 (4 mol %) in dry toluene (2 mL)
at rt. It was stirred for 15 min and then the flask was cooled
1.69–1.84 (m, 2H), 1.23 (d, J¼6.8 Hz, 6H), 0.91 (t, J¼
7.3 Hz, 3H). Anal. Calcd for C H O: C, 80.85; H, 10.18.
1
2 18
Found: C, 80.90; H, 10.21; HPLC conditions: Diacel chiral-
pak AD-H (4.6 cm I.D.ꢂ25 cm), 95:5 hexane/i-PrOH,
ꢁ
i
to ꢀ30 C. Ti(O Pr) (0.36 mL) solution in 0.5 mL toluene
4
was added dropwise to the reaction mixture. After stirring
the orange color solution for 5 min at the same temperature,
an aldehyde (1 mmol) was added and stirred for 6 h. The
reaction was quenched with 2 mL of 2 N HCl and extracted
with diethyl ether. The organic layer was washed with brine
and dried over anhydrous Na SO . The solvent was evapo-
0.5 mL/min flow rate, l¼254 nm, t (major)¼15.80 min
R
and t (minor)¼16.89 min.
R
4.2.6. (R)-1-(3-Chlorophenyl)-1-propanol (Table 2, entry
6). 94% ee; 93% yield (0.160 g); colorless liquid; [a]
2
5
D
8
a
16
+32.1 (c 1.30, CHCl ) (lit. [a]D ꢀ28.4 (c 3.74, CHCl ,
2
4
3
3
rated and the crude mixture was chromatographed over silica
gel using EtOAc and petroleum ether as eluents (5–10%).
Enantiomeric excess was determined using Chiralcel OD-H
or Chiralpak AD-H column.
98% ee)); R 0.34 (10% EtOAc in petroleum ether); spectro-
f
8
a
scopic data identical to that reported; HPLC conditions:
Diacel chiralpak AD-H (4.6 cm I.D.ꢂ25 cm), 95:5 hexane/
i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t (major)¼
R
1
5.92 min and t (minor)¼16.69 min.
R
4
8
.2.1. (R)-1-Phenyl-1-propanol (Table 2, entry 1). 96% ee;
7% yield (0.118 g); colorless liquid; [a] +45.5 (c 1.14,
2
5
4.2.7. (R)-1-(3-Fluorophenyl)-1-propanol (Table 2, entry
7). 92% ee; 84% yield (0.129 g); colorless liquid; [a]D
+32.7 (c 1.61, CHCl ); R 0.37 (10% EtOAc in petroleum
3
ether); IR (thin film): 3362, 2969, 2932, 2877, 1591, 1486,
1451, 1248, 1142, 1100, 1044, 1016, 979, 872, 787, 751,
696 cm ; H NMR (CDCl , 400 MHz) d: 7.26–7.32 (m,
D
8
a
16
25
CHCl ) (lit. [a]D ꢀ40.7 (c 1.95, CHCl , 91% ee)); R
3
3
f
0.37 (10% EtOAc in petroleum ether); spectroscopic data
identical to that reported; HPLC conditions: Diacel chiral-
f
8
a
cel OD-H (4.6 cm I.D.ꢂ25 cm), 98:2 hexane/i-PrOH,
ꢀ
1 1
0
.5 mL/min flow rate, l¼254 nm, t (major)¼28.86 min
R
3
and t (minor)¼35.70 min.
1H), 7.05–7.10 (m, 2H), 6.95 (td, J¼8.6, 2.7 Hz, 1H), 4.60
R
(
t, J¼6.4 Hz, 1H), 1.97 (br s, 1H, OH), 1.69–1.83 (m, 2H),
4
2
+
.2.2. (R)-1-(4-Chlorophenyl)-1-propanol (Table 2, entry
0.91 (t, J¼7.3 Hz, 3H). Anal. Calcd for C H FO: C,
9 11
2
5
). 96% ee; 98% yield (0.115 g); colorless liquid; [a]
70.11; H, 7.19. Found: C, 70.24; H, 7.09; HPLC conditions:
Diacel chiralpak AD-H (4.6 cm I.D.ꢂ25 cm), 95:5 hexane/
D
8
b
20
37.3 (c 1.57, CHCl ) (lit. [a]D +26.4 (c 5.27, benzene,
3
9
scopic data identical to that reported; HPLC conditions:
7% ee)); R 0.28 (10% EtOAc in petroleum ether); spectro-
i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t (major)¼
f
R
8
a
15.32 min and t (minor)¼16.28 min.
R
Diacel chiralpak AD-H (4.6 cm I.D.ꢂ25 cm), 95:5 hexane/
i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t (major)¼
4.2.8. (R)-1-(3-Chloro-4-fluorophenyl)-1-propanol (Table
2, entry 8). 93% ee; 93% yield (0.174 g); colorless liquid;
R
1
6.89 min and t (minor)¼17.62 min.
R
2
5
D 3 f
[a] +30.2 (c 1.37, CHCl ); R 0.29 (10% EtOAc in petro-
leum ether); IR (thin film): 3346, 2969, 2932, 2878, 1599,
4.2.3. (R)-1-(4-Methoxyphenyl)-1-propanol (Table 2, en-
try 3). 82% ee; 81% yield (0.135 g); colorless liquid; [a]
2
5
1499, 1460, 1409, 1338, 1253, 1096, 1054, 1016, 978, 885,
824, 793, 710 cm ; H NMR (CDCl , 400 MHz) d: 7.39 (dd,
D
8
a
16
ꢀ1 1
+
35.0 (c 1.68, CHCl ) (lit. [a]D ꢀ31.5 (c 2.1, CHCl ,
3
3
3
91% ee)); R 0.20 (10% EtOAc in petroleum ether); spectro-
scopic data identical to that reported; HPLC conditions:
J¼7.1, 2.0 Hz, 1H), 7.16–7.21 (m, 1H), 7.10 (t, J¼8.6 Hz,
1H), 4.57 (t, J¼6.4 Hz, 1H), 1.93 (br s, 1H, OH), 1.67–1.83
(m, 2H), 0.90 (t, J¼7.6 Hz, 3H). Anal. Calcd for C H ClFO:
f
8
a
Diacel chiralpak AD-H (4.6 cm I.D.ꢂ25 cm), 95:5 hexane/
9
10
i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t (major)¼
C, 57.31;H, 5.34. Found:C, 57.46;H, 5.39;HPLC conditions:
R
2
4.78 min and t (minor)¼27.73 min.
Diacel chiralpak AD-H (4.6 cm I.D.ꢂ25 cm), 95:5 hexane/
R
i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t (major)¼
R
4
.2.4. (R)-1-(3-Bromophenyl)-1-propanol (Table 2, entry
13.40 min and t (minor)¼14.28 min.
R
2
5
4). 95% ee; 92% yield (0.202 g); colorless liquid; [a]D +26.9
c 1.79, CHCl ); R 0.31 (10% EtOAc in petroleum ether); IR
(
4.2.9. (R)-1-(2,3-Difluorophenyl)-1-propanol (Table 2,
entry 9). 83% ee; 74% yield (0.128 g); colorless liquid;
[a]D +20.6 (c 1.59, CHCl ); R 0.37 (10% EtOAc in petro-
3
f
(
thin film): 3348, 3062, 2967, 2930, 2875, 1593, 1569, 1467,
425, 1342, 1195, 1076, 1016, 911, 840, 781, 670 cm ; H
ꢀ
1
1
25
1
NMR (CDCl , 400 MHz) d: 7.49–7.51 (m, 1H), 7.40 (dt,
3
f
leum ether); IR (thin film): 3350, 2971, 2935, 2880, 1626,
1595, 1485, 1277, 1203, 1095, 1043, 958, 878, 824, 786,
749, 725 cm ; H NMR (CDCl , 400 MHz) d: 7.21–7.23
3
J¼7.6, 1.7 Hz, 1H), 7.19–7.27 (m, 2H), 4.58 (t, J¼6.6 Hz,
ꢀ1 1
1
for C H BrO: C, 50.26; H, 5.15. Found: C, 50.41; H, 5.13;
H), 1.68–1.85 (m, 2H), 0.92 (t, J¼7.3 Hz, 3H). Anal. Calcd
3
(m, 1H), 7.04–7.11 (m, 2H), 4.97 (t, J¼6.3 Hz, 1H), 1.98
(br s, 1H, OH), 1.75–1.87 (m, 2H), 0.96 (t, J¼7.3 Hz, 3H).
Anal. Calcd for C H F O: C, 62.78; H, 5.85. Found: C,
62.93; H, 5.91; HPLC conditions: Diacel chiralcel OD-H
4.6 cm I.D.ꢂ25 cm), 99:1 hexane/i-PrOH, 0.5 mL/min
flow rate, l¼254 nm, t (major)¼20.44 min and t (minor)¼
9
11
HPLC conditions: Diacel chiralpak AD-H (4.6 cm
I.D.ꢂ25 cm), 95:5 hexane/i-PrOH, 0.5 mL/min flow rate,
l¼254 nm, t (major)¼16.88 minandt (minor)¼17.66 min.
9
10 2
R
R
(
4.2.5. (R)-1-(4-Isopropylphenyl)-1-propanol (Table 2,
entry 5). 93% ee; 98% yield (0.174 g); colorless liquid;
R
R
22.74 min.
2
5
[
a] +35.4 (c 1.68, CHCl ); R 0.34 (10% EtOAc in petro-
D 3 f
leum ether); IR (thin film): 3362, 2962, 2930, 2873, 1661,
613, 1511, 1460, 1418, 1330, 1208, 1094, 1047, 1013,
4.2.10. (R)-1-(3,5-Dimethylphenyl)-1-propanol (Table 2,
entry 10). 93% ee; 83% yield (0.136 g); colorless liquid;
1

A. Bisai et al. / Tetrahedron 63 (2007) 598–601
601
2
5
[a] +31.8 (c 0.85, CHCl ); R 0.31 (10% EtOAc in petro-
leum ether); IR (thin film): 3357, 3012, 2965, 2926, 2872,
References and notes
D
3
f
1
7
6
1
606, 1460, 1348, 1161, 1094, 1044, 1022, 976, 897, 847,
08 cm ; H NMR (CDCl , 400 MHz) d: 6.94 (s, 2H),
1. Reviews: (a) Yus, M.; Ramon, D. J. Pure Appl. Chem. 2005, 77,
2111–2119; (b) Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed.
2004, 43, 284–287; (c) Soai, K.; Niwa, S. Chem. Rev. 1992,
92, 833–856; (d) Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101,
757–824.
ꢀ
1 1
3
.91 (s, 1H), 4.51 (t, J¼6.6 Hz, 1H), 2.31 (s, 6H), 1.67–
.85 (m, 2H), 0.91 (t, J¼7.3 Hz, 3H). Anal. Calcd for
C H O: C, 80.44; H, 9.82. Found: C, 80.60; H, 9.80;
1
1 16
HPLC conditions: Diacel chiralcel OD-H (4.6 cm I.D.ꢂ
2. For some recent selected papers in this area, see: (a) Cozzi, P. G.;
Kotrusz, P. J. Am. Chem. Soc. 2006, 128, 4940–4941; (b) Huang,
J.; Ianni, J. C.; Antoline, J. E.; Hsung, R. P.; Kozlowski, M. C.
Org. Lett. 2006, 8, 1565–1568; (c) Roudeau, R.; Pardo, D. G.;
Cossy, J. Tetrahedron 2006, 62, 2388–2394; (d) Richmond,
M. L.; Seto, C. T. J. Org. Chem. 2003, 68, 7505–7508; (e)
DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2002, 4, 3781–
3784; (f) Nugent, W. A. Org. Lett. 2002, 4, 2133–2136; (g)
DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2001, 3, 3053–
3056.
3. Review: Walsh, P. J. Acc. Chem. Res. 2003, 36, 739–749.
4. (a) Yoshioka, M.; Kawakita, T.; Ohno, M. Tetrahedron Lett.
1989, 30, 1657–1660; (b) Takahashi, H.; Kawakita, T.;
Yoshioka, M.; Kobayashi, S.; Ohno, M. Tetrahedron Lett.
1989, 30, 7095–7098; (c) Takahashi, H.; Kawakita, T.; Ohno,
M.; Yoshioka, M.; Kobayashi, S. Tetrahedron 1992, 48, 5691–
5700; (d) Rozema, M. J.; Sidduri, A.; Knochel, P. J. Org.
Chem. 1992, 57, 1956–1958; (e) Brieden, W.; Ostwald, R.;
Knochel, P. Angew. Chem., Int. Ed. Engl. 1993, 32, 582–584;
(f) Nowotny, S.; Vettel, S.; Knochel, P. Tetrahedron Lett. 1994,
35, 4539–4540; (g) Ostwald, R.; Chavant, P.; Stadtmuller, H.;
Knochel, P. J. Org. Chem. 1994, 59, 4143–4153; (h) Lutz, C.;
Knochel, P. J. Org. Chem. 1997, 62, 7895–7898; (i) Ho, D. E.;
Betancort, J. M.; Woodmansee, D. H.; Larter, M. L.; Walsh,
P. J. Tetrahedron Lett. 1997, 38, 3867–3870; (j) Pritchett, S.;
Woodmansee, D. H.; Davis, T. J.; Walsh, P. J. Tetrahedron
Lett. 1998, 39, 5941–5942.
2
5 cm), 99.5:0.5 hexane/i-PrOH, 0.5 mL/min flow rate,
l¼254 nm, tR (major)¼20.33 min and tR (minor)¼
2
2.15 min.
4.2.11. (R)-1-(3-Methylphenyl)-1-propanol (Table 2, en-
try 11). 95% ee; 94% yield (0.141 g); colorless liquid;
2
5
8a
16
[
CHCl , 44% ee)); R 0.31 (10% EtOAc in petroleum ether);
a] +37.9 (c 1.76, CHCl ) (lit. [a]D ꢀ12.1 (c 2.43,
D
3
3 f
8
a
spectroscopic data identical to that reported; HPLC condi-
tions: Diacel chiralcel OD-H (4.6 cm I.D.ꢂ25 cm), 98:2 hex-
ane/i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t (major)¼
R
1
5.34 min and t (minor)¼18.45 min.
R
4
.2.12. (R)-1-Cyclohexyl-propanol (Table 2, entry 12).
2
5
9
6% ee; 56% yield (0.085 g); colorless liquid; [a] +7.0
D
8
b
20
(c 1.04, CHCl ) (lit. [a]D +6.35 (c 3.0, CHCl , 95%
3 3
ee)); H NMR (CDCl , 400 MHz) d: 3.27–3.28 (m, 1H),
1
3
1
0
.73–1.79 (m, 2H), 1.63–1.68 (m, 1H), 1.52–1.54 (m, 1H),
.99–1.43 (m, 9H), 0.95 (t, J¼7.4 Hz, 3H). Anal. Calcd for
C H O: C, 76.00; H, 12.76. Found: C, 76.19; H, 12.80.
9 18
4.2.13. 4-Methoxybenzoate derivative of (R)-1-cyclo-
hexyl-propanol. Yield 65% (0.046 g); colorless liquid;
2
5
1
[
a] +13.6 (c 1.02, CHCl ); H NMR (CDCl , 400 MHz)
D 3 3
d: 8.02 (d, J¼8.8 Hz, 2H), 6.92 (d, J¼9.0 Hz, 2H), 4.90–
4
5
7
.92 (m, 1H), 3.86 (s, 3H), 1.59–1.80 (m, 8H), 1.06–1.33 (m,
H), 0.91 (t, J¼7.3 Hz, 3H). Anal. Calcd for C H O : C,
1
7 24 3
5. For structure and mechanistic aspect, see: (a) Pritchett, S.;
Woodmansee, D. H.; Gantzel, P.; Walsh, P. J. J. Am. Chem.
Soc. 1998, 120, 6423–6424; (b) Royo, E.; Betancort, J. M.;
Davis, T. J.; Caroll, P.; Walsh, P. J. Organometallics 2000, 19,
4840–4851; (c) Balsells, J.; Betancort, J. M.; Walsh, P. J.
Angew. Chem., Int. Ed. 2000, 39, 3428–3429.
3.88; H, 8.75. Found: C, 74.01; H, 8.80; HPLC conditions:
Diacel chiralpak AD-H (4.6 cm I.D.ꢂ25 cm), 99.8:0.2
hexane/i-PrOH, 0.5 mL/min flow rate, l¼254 nm, t
R
(
major)¼24.40 min and t (minor)¼30.81 min.
R
6
. Whitesell, J. K. Chem. Rev. 1989, 89, 1581–1590.
7. (a) Bisai, A.; Prasad, B. A. B.; Singh, V. K. Tetrahedron Lett.
005, 46, 7935–7939; (b) Bisai, A.; Prasad, B. A. B.; Singh,
Acknowledgements
2
V.K.S. thanks the Department of Science and Technology,
Government of India for a research grant. A.B. and P.K.S.
thank the Council of Scientific and Industrial Research,
New Delhi, for research fellowships.
V. K. ARKIVOC 2007, (Part v), 20–37.
8. (a) Chen, Y.-J.; Lin, R.-X.; Chen, C. Tetrahedron: Asymmetry
2004, 15, 3561–3571; (b) Dai, W.-M.; Zhu, H.-J.; Hao, X.-J.
Tetrahedron: Asymmetry 2000, 11, 2315–2337.