A new chiral catalytic source with an N-P=O structural framework containing a proximal hydroxyl group for the borane-mediated asymmetric reduction of prochiral ketones

Article abstract of DOI:10.1016/j.tetasy.2003.11.002

(5S)-2-[(1R,2R,3S,5R)-2-Hydroxy-2,6,6-trimethylbicyclo[3.1.1] heptan-3-yloxy]-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo[3.3.0]octane has been successfully employed as a novel chiral catalytic source (4mol%) for borane-mediated asymmetric reduction of prochiral ketones thus providing the resulting secondary alcohols with up to 96% enantiomeric excess.

Full text of DOI:10.1016/j.tetasy.2003.11.002

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 47–52
A new chiral catalytic source with an N–P@O structural framework
containing a proximal hydroxyl group for the borane-mediated
asymmetric reduction of prochiral ketones
Deevi Basavaiah,* Gone Jayapal Reddy and Vanampally Chandrashekar
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Received 6 August 2003; revised 22 October 2003; accepted 4 November 2003
Abstract—(5S)-2-[(1R,2R,3S,5R)-2-Hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yloxy]-1,3-diaza-2-phospha-2-oxo-3-phenylbicy-
clo[3.3.0]octane has been successfully employed as a novel chiral catalytic source (4 mol %) for borane-mediated asymmetric
reduction of prochiral ketones thus providing the resulting secondary alcohols with up to 96% enantiomeric excess.
ꢀ 2003 Elsevier Ltd. All rights reserved.
1. Introduction
cyclo(3.3.0)octane 1 as a catalytic source for the borane-
mediated asymmetric reduction of prochiral ketones to
provide the resulting secondary alcohols in 59–96%
enantiomeric excess.
Boron based chiral reducing agents/catalysts occupy a
special place in chiral chemistry, particularly in asym-
metric reductions, because of their extensive use in effi-
ciently and conveniently transforming prochiral ketones
into the corresponding secondary alcohols with high
enantioselectivities.1–11 The recent elegant work of Wills
and coworkers12–17 on the applications of molecules
containing the N–P@O structural framework as novel
chiral catalysts for borane-mediated asymmetric reduc-
tion of prochiral ketones has generated a new inter-
est18–21 in the chemistry of asymmetric reductions. In
continuation of our work in the development of novel
chiral catalytic sources containing N–P@O structural
framework for borane-mediated asymmetric reduc-
tions,20;21 we herein report the application of (5S)-2-
[(1R,2R,3S,5R)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]-
heptan-3-yloxy]-1,3-diaza-2-phospha-2-oxo-3-phenylbi-
Recently, we have reported the applications of (1R,2R)-
1,2-bis[{(5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo-
[3.3.0]octan-2-yl}methylamino]cyclohexane 2, 1,4-bis-
[(5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo[3.3.0]-
octan-2-yl]piperazine 3 and (2S,5S)-1,3-diaza-2-phospha-
2-oxo-2-chloro-3-phenylbicyclo[3.3.0]octane 4 as useful
chiral catalysts/sources for borane-mediated asymmetric
reduction of prochiral a-halo ketones.20;21 The work of
Wills et al.,12;22 Buono et al.,18;23 on the role of a proximal
hydroxyl group in the catalysts in the asymmetric
reduction of prochiral ketones, has led us to design a
catalyst containing such a proximal hydroxyl group. We
planned to prepare the catalyst 1 and study its catalytic
applications in the reduction of prochiral ketones.
H
Ph
N
P
H
3C
N
O
O
N
H
N
O
O
N
P
N
N
P
O
OH
N
N
P
H
N
N
O
N
H
N
H
N
Cl
P
P
N
H
3C
Ph
Ph
Ph
O
N
Ph
H
Ph
4
3
1
2
* Corresponding author. Tel.: +91-40-3010221; fax: +91-40-3012460; e-mail: dbsc@uohyd.ernet.in
0957-4166/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.002

48
D. Basavaiah et al. / Tetrahedron: Asymmetry 15 (2004) 47–52
2. Results and discussion
We then employed a representative class of prochiral
a-halo ketones 5b–g for a borane-mediated asymmetric
reduction under the catalytic influence of the molecule 1
(4 mol %) to provide the resulting secondary alcohols
6b–g with high enantiomeric excesses (86–96%) (Eq. 3,
Table 2). Enantiomeric excesses of the chiral alcohols
6a–d were determined by HPLC analysis using the chiral
column (Chiralcel-OD) with reference to the corre-
sponding racemic alcohols while the enantiomeric puri-
ties of alcohols 6e–g were determined by 1H NMR
analysis of their acetates in the presence of a chiral shift
reagent, [Eu(hfc)3], with reference to their corresponding
racemic acetates.
The desired catalyst 1 was prepared via treatment of 4
with ())-pinane-2,3-diol in the presence of NaH (Eq. 1).
We first examined the borane-mediated asymmetric
reduction of phenacyl bromide under the influence of 1
with different catalytic amounts (Eq. 2, Table 1). The
best results were seen when phenacyl bromide 5a was
treated with borane-dimethyl sulfide under the influence
of 1 (4 mol %) in refluxing toluene for 1 h, providing the
desired alcohol (S)-2-bromo-1-phenylethanol 6a in 88%
yield with 91% enantiomeric excess.
OH
With a view to examine the catalytic efficiency of 1, we
also performed the reduction of acetophenone 5h under
the influence of 1 (4 mol %) with BH3ÆSMe2. The
resulting (R)-1-phenylethanol 6h was obtained in 63%
enantiomeric purity. To understand the applicability of
this catalyst 1, we subjected the representative prochiral
ketones 5i–l to a borane-mediated reduction under the
influence of catalyst 1 (4 mol %). The resulting sec-
ondary alcohols 6i–l were obtained in 59–67% enan-
tiomeric excesses (Eqs. 4 and 5, Table 3). The
enantiomeric excesses of the chiral alcohols 6h–l were
determined by HPLC analysis using the chiral column
[Chiralcel-OD (6h, i, k, l) or Chiralcel-OD-H (6j)] with
reference to the corresponding racemic alcohols. From
these studies it is quite clear that a-halo ketones pro-
vide much better enantioselectivities than simple aryl
alkyl ketones.
OH
H
O
OH
N
N
P
H
O
N
Cl
P
N
Ph
NaH, DMF
90 min, 65%
O
Ph
1
4
ð1Þ
OH
O
Br
Br
1.0 eq. BH3.SMe2 / 1 (cat.)
Toluene, 110 oC, 1 h
6a
5a
ð2Þ
O
OH
1.0 eq. BH3.SMe2 / 1 (4 mol%)
R
Ar
Table 1. Asymmetric reduction of phenacyl bromide 5aa
Ar
R
Toluene, 110 ˚C, 1 h
76-85%
Entry
Catalyst 1 Yield
(mol %)
Enantiomeric
purity (%)c 6a
Configu-
rationd
6h-k
5h-k
(%)b 6a
59-67% ee
R = Me, Et, Pr
Ar = phenyl, naphth-1-yl
1
2
3
4
5
6
2
81
71
91
87
S
S
S
S
S
S
3
4
8087
88
ð4Þ
5
8089
84
7
1086
O
OH
83
1.0 eq. BH3.SMe2 / 1 (4 mol%)
a All reactions were carried out on a 0.5 mM scale of phenacyl bromide
with 0.5 mM of BH3ÆSMe2 in the presence of 1 in toluene for 1 h at
110 ꢁC.
Toluene, 110 ˚C, 1 h
71%
6l
70% ee
b Isolated yields of alcohols after purification by column chromato-
graphy (silica gel, 5% ethyl acetate in hexanes).
c Determined by HPLC analysis using the chiral column, Chiralcel-
OD.
5l
ð5Þ
It is worth comparing these results (for reduction of
a-halo ketones) with those of our earlier catalysts.
d The absolute configuration was assigned by comparison of the sign of
the specific rotation with that of the reported molecule.24
O
OH
1 (4 mol%)
/
1.0 eq. BH3.SMe2
X
X
Ar
Ar
Toluene, 110 ˚C, 1 h
ð3Þ
88-94%
6a-g
86-96% ee
Ar = phenyl,4-methylphenyl, 4-bromophenyl, 4-chlorophenyl, 4-nitrophenyl
5a-g
X = Br, Cl

D. Basavaiah et al. / Tetrahedron: Asymmetry 15 (2004) 47–52
Table 2. Asymmetric reduction of prochiral a-halo ketonesa
49
25
D
Substrate
Ar
X
Product
Yield (%)b
½aŠ
Conf.c
Ee (%)d
5a
5b
5c
5d
5e
5f
Phenyl
Phenyl
Br
Cl
Br
Cl
Br
Br
Br
6a
6b
6c
6d
6e
6f
88
91
+41.5 (c 1.2, CHCl3)
S
S
S
S
S
S
S
91
86
+42.1 (c 1.0, C6H12
)
4-Methylphenyl
4-Methylphenyl
4-Bromophenyl
4-Chlorophenyl
4-Nitrophenyl
94
92
+39.9 (c 1.1, CHCl3)
+44.0( c 1.0, CHCl3)
+33.8 (c 2.4, CHCl3)
+39.0( c 1.0, CHCl3)
c 1.0, CHCl3)
91
88
89
92
96e
89e
92e
5g
6g
90+33.2 (
a All reactions were carried out on a 1 mM scale of a-halo ketone with 1 mM of BH3ÆSMe2 in the presence of 1 (4 mol %) in toluene for 1 h at 110 ꢁC.
b Isolated yields of alcohols after purification by column chromatography (silica gel, 5% ethyl acetate in hexanes).
c The absolute configuration was assigned by comparison of the signs of specific rotations with those reported.20;21;24;25
d Determined by HPLC analysis using the chiral column, Chiralcel-OD.
e
1
Enantiomeric excesses were determined by H NMR (200 MHz) analysis of the acetates in the presence of the chiral shift reagent, [Eu(hfc)3], with
reference to the corresponding racemic acetates.
Table 3. Enantioselective reduction of prochiral ketonesa
25
D
Entry
Ketone
Product
Yield (%)b
½aŠ
Conf.c
Ee (%)d
1
2
3
4
5
Acetophenone 5h
Propiophenone 5i
Butyrophenone 5j
1-Acenaphthone 5k
a-Tetralone 5l
6h
6i
(
80+29.0
c 1.0, MeOH)
R
R
R
R
R
63
67
59e
63
70
85
83
76
71
+30.7 (c 1.9, CHCl3)
+28.0( c 0.7, benzene)
+50.3 (c 1.08, ether)
)16.4 (c 0.75, MeOH)
6j
6k
6l
a All reactions were carried out on a 1 mM scale of prochiral ketone with 1 mM of BH3ÆSMe2 in the presence of 1 (4 mol %) in toluene for 1 h at 110 ꢁC.
b Isolated yields of alcohols after purification by column chromatography (silica gel, 5% ethyl acetate in hexanes).
c The absolute configuration was assigned by the comparison of the signs of the specific rotations with those reported.26–28
d Enantiomeric excesses were determined by the HPLC analysis using the chiral column, Chiralcel-OD.
e Enantiomeric excess was determined by the HPLC analysis using the chiral column, Chiralcel-OD-H.
Though catalyst 3 offers slightly better enantioselectiv-
ities (90–95% ee), the reaction requires more catalyst
(30mol %). 20 The present catalyst 1 provides (86–96%
ee with 4 mol % 1) slightly better enantioselectivities
than the chiral source 4 (81–91% ee with 5 mol % 4).21
From these comparisons it appears that proximal
hydroxyl group has some advantage on borane-medi-
ated asymmetric reductions of prochiral a-halo
ketones.29
developed a novel chiral catalytic source for borane-
mediated asymmetric reductions of prochiral ketones, in
particular a-halo ketones, to provide the resulting sec-
ondary alcohols in up to 96% enantiomeric excesses.
Studies are currently underway to understand the
mechanism of the reduction process.
3. Experimental
In an attempt to understand the mechanistic pathway of
the reduction process, we attempted to recover the cat-
alyst by carrying out the reduction of acetophenone
(2 mM) with BH3ÆSMe2 (2 mM) in the presence of cat-
alyst 1 (0.08 mM). However, we found that the catalyst
was not recoverable intact in the reaction as shown by
the 31P NMR spectrum of the reaction mixture, which
showed broad signals at d 80–115 whereas the 31P NMR
spectrum of the original catalyst showed a single peak at
d 19.88. To understand the nature of the catalyst we also
treated 1 (0.1 mM) with BH3ÆSMe2 (0.2 mM) in toluene
(0.5 mL) for 10 min at reflux and recorded the 31P NMR
spectrum of the reaction mixture, which showed broad
signals at d 85–125. Since the enantioselectivities were
also reasonably high in the case of acetophenone 5h and
the other ketones 5i–l, it suggests that the diazaborol-
idine was not generated during the reaction process.21;30
From these studies, it is clear that the catalyst was not
intact, as it probably decomposed during the course of
reaction. Though the nature of the catalyst and the
reaction pathway are not clearly understood, we have
All melting points were recorded on a Superfit (India)
capillary melting point apparatus and are uncorrected.
IR spectra were recorded on a Jasco-FT-IR model 5300
or Perkin–Elmer model 1310spectrometer. 1H NMR
(200 MHz) and 13C NMR (50MHz) spectra were
recorded in deuterochloroform (CDCl3) on a Bruker-
AC-200 spectrometer using tetramethylsilane (TMS,
d ¼ 0) as the internal standard. 31P NMR (81 MHz)
spectra were recorded on a Bruker-AC-200 spectrometer
using 85% H3PO4 (d ¼ 0ppm) as the external standard.
Elemental analyses were recorded on a Perkin–Elmer
240C-CHN analyzer. Mass spectra were recorded on an
HP 5989 A (LC) (CI method) mass spectrometer. HPLC
analyses of alcohols were carried out on a Shimadzu
LC-10AD instrument using a chiral column (Chiralcel-
OD or Chiralcel-OD-H). Optical rotations were mea-
sured on a Jasco DIP 370digital polarimeter. We have
previously prepared 6a–f molecules and reported the
spectral data.20 The present spectral data (IR, 1H NMR,
13C NMR) of 6a–f is in agreement with the earlier data.

50
D. Basavaiah et al. / Tetrahedron: Asymmetry 15 (2004) 47–52
3.1. (5S)-2-[(1R,2R,3S,5R)-2-Hydroxy-2,6,6-trimeth-
ylbicyclo[3.1.1]heptan-3-yloxy]-1,3-diaza-2-phospha-
2-oxo-3-phenylbicyclo[3.3.0]octane 1
3.3. (S)-2-Chloro-1-phenylethanol 6b
25
Colorless oil; yield 91%; ½aŠ +42.1 (c 1.0, cyclohexane)
D
25
D
{lit.24 ½aŠ )48.1 (c 1.73, cyclohexane), (R)-configura-
To a stirred suspension of oil free NaH (2.0mM, 48 mg)
in DMF, was added slowly (1R,2R,3S,5R)-2,6,6-tri-
methylbicyclo[3.1.1]heptane-2,3-diol (1.0mM, 170mg)
at room temperature. After 5 min, the reaction mixture
was cooled to 0 ꢁC and (2S,5S)-1,3-diaza-2-phospha-2-
oxo-2-chloro-3-phenylbicyclo(3.3.0)octane 4 (1.10mM,
282.7 mg) added slowly. Then the reaction mixture was
stirred for 90min at room temperature and quenched
with water and diluted with ether (10mL). The organic
layer was separated and the aqueous layer extracted
with ether (3 · 20mL). The combined organic layer was
dried over anhydrous sodium sulfate and the solvent
removed under reduced pressure. The crude product
thus obtained, was purified by column chromatography
(silica gel, 25% ethyl acetate in hexanes) followed by
crystallization (40% ethyl acetate in hexanes) to afford
the desired (5S)-2-[(1R,2R,3S,5R)-2-hydroxy-2,6,6-
trimethylbicyclo[3.1.1]heptan-3-yloxy]-1,3-diaza-2-phos-
tion, 100% ee}; 86% ee, the enantiomeric purity was
determined by HPLC using a chiral column [Chiralcel-
OD, 90:10 hexanes/i-PrOH, 1.0mL/min, 254 nm, reten-
tion times: 7.89 min (S) and 9.09 min (R)].
3.4. (S)-2-Bromo-1-(4-methylphenyl)ethanol 6c
25
Viscous liquid; yield 94%; ½aŠ +39.9 (c 1.1, CHCl3)
D
25
D
{lit.20 ½aŠ +41.8 (c 1.0, CHCl3), (S)-configuration, 95%
ee}; 91% ee, the enantiomeric excess was determined by
HPLC using a chiral column [Chiralcel-OD, 97.5:2.5
hexanes/i-PrOH, 1.0mL/min, 254 nm, retention times:
16.15 min (S) and 19.36 min (R)].
3.5. (S)-2-Chloro-1-(4-methylphenyl)ethanol 6d
pha-2-oxo-3-phenylbicyclo[3.3.0]octane as white needles
25
Colorless oil; yield 92%; ½aŠ +44.0( c 1.0, CHCl3) {lit.20
25
D
D
(254 mg, 65%); mp 138–140 ꢁC; ½aŠ )22.3 (c 1.05,
25
D
½aŠ +47.2 (c 1.1, CHCl3), (S)-configuration, 92% ee};
CHCl3); IR (KBr): 3335, 1602, 1523, 1325, 1242 cmÀ1
;
88% ee, the enantiomeric excess was determined by
HPLC using a chiral column [Chiralcel-OD, 97.5:2.5
hexanes/i-PrOH, 1.0mL/min, 254 nm, retention times:
14.64 min (S) and 16.80min ( R)].
1H NMR: d 0.89 (s, 3H), 1.31 (s, 3H), 1.41–2.57 (m,
13H), 2.95–3.12 (m, 1H), 3.16–3.48 (m, 3H), 4.02–4.21
(m, 1H), 4.53–4.78 (m, 2H), 6.58–6.72 (m, 3H), 7.08–
7.23 (m, 2H); 13C NMR: d 24.17, 24.77 (d, J ¼ 9:1 Hz),
26.01, 27.03, 28.72, 30.06 (d, J ¼ 8:9 Hz), 34.89 (d,
J ¼ 5:8 Hz), 38.95, 39.64, 47.11 (d, J ¼ 3:5 Hz), 48.88,
51.69 (d, J ¼ 8:2 Hz), 58.81 (d, J ¼ 6:6 Hz), 76.73,
86.22, 112.45, 116.67, 129.04, 148.35; 31P NMR: d 19.88;
MS (LC-CI) (m=z): 390(M) þ, 391 (M+H)þ; Anal. Calcd
for C21H31N2O3P: C, 64.59; H, 8.00; N, 7.17. Found: C,
64.48; H, 8.05; N, 7.12%.
3.6. (S)-2-Bromo-1-(4-bromophenyl)ethanol 6e
25
White solid; yield 89%; mp 71–72 ꢁC; ½aŠ +33.8 (c 2.4,
D
25
D
ration, 94% ee}; 96% ee, the enantiomeric excess was
CHCl3) {lit.25 ½aŠ )31.0( c 2.9, CHCl3), (R)-configu-
1
determined by H NMR spectral analysis of the corre-
sponding acetate in the presence of chiral shift reagent,
Eu(hfc)3, with reference to the racemic acetate.20
3.2. Representative procedure. Asymmetric reduction
of phenacyl bromide: synthesis of (S)-2-bromo-
1-phenylethanol 6a
3.7. (S)-2-Bromo-1-(4-chlorophenyl)ethanol 6f
To
a stirred solution of (5S)-2-[(1R,2R,3S,5R)-2-
hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yloxy]-
1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo[3.3.0]octane
1 (0.04 mM, 15.6 mg) in toluene (5 mL) was added
borane-dimethyl sulfide (1.0mM, 76 mg) at room tem-
perature and the reaction mixture heated to 110 ꢁC.
Once the temperature was stabilized at 110 ꢁC, phena-
cyl bromide (1.0mM, 199 mg) in toluene (2 mL) was
added dropwise over a period of 10min after which
stirring continued for a further 1 h (monitored by
TLC). The reaction mixture was then allowed to cool
to room temperature and quenched with methanol.
The solvent was removed under reduced pressure and
the residue obtained, purified by column chromato-
graphy (silica gel, 5% ethyl acetate in hexanes) to
25
Colorless oil; yield 92%; ½aŠ +39.0( c 1.0, CHCl3) {lit.20
D
25
D
89% ee, the enantiomeric excess was determined by H
½aŠ +38.6 (c 1.15, CHCl3), (S)-configuration, 91% ee};
1
NMR spectral analysis of the corresponding acetate in
the presence of chiral shift reagent, Eu(hfc)3, with ref-
erence to the racemic acetate.20
3.8. (S)-2-Bromo-1-(4-nitrophenyl)ethanol 6g
25
Light yellow solid; yield 90%; mp 78–80 ꢁC; ½aŠ +33.2
D
25
D
configuration, 91% ee}; 92% ee, the enantiomeric excess
(c 1.0, CHCl3) {lit.21 ½aŠ +32.0( c 1.0, CHCl3), (S)-
1
was determined by H NMR spectral analysis of the
corresponding acetate in the presence of chiral shift
reagent, Eu(hfc)3, with reference to the racemic acetate;
provide the desired (S)-2-bromo-1-phenylethanol 6a
25
D
in 88% yield (177 mg) as a colorless oil; ½aŠ +41.5 (c
25
D
1.2, CHCl3) {lit.24 ½aŠ )39.0( c 8.00, CHCl3), (R)-
IR (KBr): 3543 cmÀ1
;
1H NMR: d 2.77 (d, 1H,
configuration, 93% ee}; 91% ee, the enantiomeric ex-
cess was determined by HPLC using a chiral column
[Chiralcel-OD, 90:10 hexanes/i-PrOH, 1.0mL/min,
254 nm, retention times: 8.12 min (S) and 9.60min ( R)].
J ¼ 3:6 Hz), 3.45–3.73 (m, 2H), 4.98–5.10(m, 1H), 7.58
(d, 2H, J ¼ 8:6 Hz), 8.23 (d, 2H, J ¼ 8:6 Hz); 13C NMR:
d 39.13, 72.68, 123.80, 127.01, 147.54, 147.83.

D. Basavaiah et al. / Tetrahedron: Asymmetry 15 (2004) 47–52
51
3.9. (S)-1-Acetoxy-2-bromo-1-(4-nitrophenyl)ethane
3.14. (R)-1,2,3,4-Tetrahydronaphth-1-ol 6l
25
Colorless oil; yield 71%; ½aŠ )16.4 (c 0.75, MeOH)
Light yellow solid; yield 75%; mp 102–105 ꢁC; ½aŠ25 +46.6
(c 0.9, CHCl3); IR (KBr): 1751 cmÀ1; 1H NMR: dD2.18 (s,
3H), 3.58–3.74 (m, 2H), 5.99–6.08 (m, 1H), 7.55 (d, 2H,
J ¼ 8:6 Hz) 8.25 (d, 2H, J ¼ 8:6 Hz); 13C NMR: 20.87,
33.38, 73.70, 124.00, 127.73, 144.61, 148.26, 169.56.
D
25
D
{lit.26 ½aŠ )23.14 (c 1.3, MeOH), (R)-configuration,
94% ee}; 70% ee, the enantiomeric excess was deter-
mined by HPLC using a chiral column [Chiralcel-OD,
97.5:2.5 hexanes/i-PrOH, 0.4 mL/min, 254 nm, retention
times 35.50min ( S) and 39.52 min (R)]; IR (neat):
3356 cmÀ1; 1H NMR: d 1.45–2.14 (m, 5H), 2.61–2.92 (m,
2H), 4.70–4.92 (m, 1H), 7.04–7.33 (m, 3H), 7.38–7.56
(m, 1H); 13C NMR: d 18.84, 29.19, 32.21, 67.96, 126.02,
127.38, 128.60, 128.84, 137.00, 138.86.
3.10. (R)-1-Phenylethanol 6h
25
Colorless oil; yield 80%; ½aŠ +29.0( c 1.0, MeOH) {lit.26
D
25
D
½aŠ +44.12 (c 3.0, MeOH), (R)-configuration, 97% ee};
63% ee, the enantiomeric excess was determined by
HPLC using a chiral column [Chiralcel-OD, 95:5 hex-
anes/i-PrOH, 1.0mL/min, 254 nm, retention times:
Acknowledgements
8.76 min (R) and 10.72 min (S)]; IR (neat): 3362 cmÀ1
1H NMR: d 1.46 (d, 3H, J ¼ 6:8 Hz), 2.10(br s, 1H),
;
We thank CSIR (New Delhi) for funding this project.
We thank UGC (New Delhi) for recognizing our Uni-
versity of Hyderabad as ꢀUniversity with potential for
excellence (UPE)ꢁ and for generous funding and also for
the Special Assistance Program in Organic Chemistry in
the School of Chemistry, University of Hyderabad,
Hyderabad. G.J.R. and V.C. also thank CSIR (New
Delhi) for their research fellowships.
4.84 (q, 1H, J ¼ 6:8 Hz), 7.18–7.41 (m, 5H); 13C NMR:
d 25.11, 70.43, 125.45, 127.49, 128.54, 145.94.
3.11. (R)-1-Phenylpropan-1-ol 6i
25
Colorless oil; yield 85%; ½aŠ +30.7 (c 1.9, CHCl3) {lit.26
D
25
D
½aŠ +43.03 (c 5.1, CHCl3), (R)-configuration, 96% ee};
67% ee, the enantiomeric purity was determined by
HPLC using a chiral column [Chiralcel-OD, 95:5 hex-
anes/i-PrOH, 1.0mL/min, 254 nm, retention times:
References and Notes
1. Brown, H. C.; Jadhav, P. K.; Singaram, B. In Modern
Synthetic Methods; Scheffold, R., Ed.; Springer: Heidel-
berg, 1986; Vol. 4, pp 307–356.
2. Brown, H. C.; Ramachandran, P. V. Acc. Chem. Res.
1992, 25, 16–24.
8.32 min (R) and 10.05 min (S)]; IR (neat): 3373 cmÀ1
;
1H NMR: d 0.93 (t, 3H, J ¼ 7:0Hz), 1.68–1.93 (m, 3H),
4.61 (t, 1H, J ¼ 6:8 Hz), 7.22–7.44 (m, 5H); 13C NMR: d
10.12, 31.85, 75.93, 126.02, 127.41, 128.35, 144.66.
3. Ramachandran, P. V.; Brown, H. C.; Pitre, S. Org. Lett.
2001, 3, 17–18.
4. Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37,
1986–2012.
3.12. (R)-1-Phenylbutan-1-ol 6j
5. Singh, V. K. Synthesis 1992, 605–617.
6. Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763–784.
7. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc.
1987, 109, 5551–5553.
8. Prasad, K. R. K.; Joshi, N. N. J. Org. Chem. 1996, 61,
3888–3889.
9. Zhou, H.; Lu, S.; Xie, R.; Chan, A. S. C.; Yang, T. K.
Tetrahedron Lett. 2001, 42, 1107–1110.
10. Delogu, G.; Fabbri, D.; Candia, C.; Patti, A.; Pedotti, S.
Tetrahedron: Asymmetry 2002, 13, 891–898.
11. Cho, B. T.; Choi, O. K.; Kim, D. J. Tetrahedron:
Asymmetry 2002, 13, 697–703.
25
Colorless oil; yield 83%; ½aŠ +28.0( c 0.7, benzene)
D
25
D
{lit.27 ½aŠ )45.2 (c 4.81, benzene), (S)-configuration,
100% ee}; 59% ee, the enantiomeric excess was deter-
mined by HPLC using a chiral column [Chiralcel-OD-
H, 95:5 hexanes/i-PrOH, 0.7 mL/min, 254 nm, retention
times: 12.30min ( R) and 13.10min ( S)]; IR (neat):
1
3300 cmÀ1; H NMR: d 0.93 (t, 3H, J ¼ 7:0Hz), 1.21–
1.91 (m, 5H), 4.68 (t, 1H, J ¼ 6:6 Hz), 7.19–7.40(m,
5H); 13C NMR: d 13.93, 19.00, 41.23, 74.33, 125.93,
127.38, 128.36, 145.02.
12. Gamble, M. P.; Studley, J. R.; Wills, M. Tetrahedron Lett.
1996, 37, 2853–2856.
13. Burns, B.; Gamble, M. P.; Simm, A. R. C.; Studley, J. R.;
Alcock, N. W.; Wills, M. Tetrahedron: Asymmetry 1997, 8,
73–78.
14. Burns, B.; King, N. P.; Tye, H.; Studley, J. R.; Gamble,
M. P.; Wills, M. J. Chem. Soc., Perkin Trans. 1 1998,
1027–1038.
15. Gamble, M. P.; Studley, J. R.; Wills, M. Tetrahedron:
Asymmetry 1996, 7, 3071–3074.
16. Burns, B.; Studley, J. R.; Wills, M. Tetrahedron Lett. 1993,
34, 7105–7106.
3.13. (R)-1-(Naphth-1-yl)ethanol 6k
25
Colorless oil; yield 76%; ½aŠ +50.3 (c 1.08, ether) {lit.28
D
25
D
½aŠ +82.1 (c 1.0, ether), (R)-configuration, >99% ee};
63% ee, the enantiomeric excess was determined by
HPLC using a chiral column [Chiralcel-OD, 95:5 hex-
anes/i-PrOH, 1.0mL/min, 254 nm, retention times:
24.44 min (S) and 37.72 min (R)]; IR (neat): 3368 cmÀ1
;
1H NMR: d 1.64 (d, 3H, J ¼ 6:0Hz), 2.65 (br s, 1H),
5.59 (q, 1H, J ¼ 6:0Hz), 7.36–8.20 (m, 7H); 13C NMR:
24.41, 67.04, 122.11, 123.28, 125.57, 126.04, 127.89,
128.94, 130.36, 133.89, 144.51.
17. Burns, B.; King, N. P.; Studley, J. R.; Tye, H.; Wills, M.
Tetrahedron: Asymmetry 1994, 5, 801–804.
18. Brunel, J. M.; Legrand, O.; Buono, G. Eur. J. Org. Chem.
2000, 3313–3321.

52
D. Basavaiah et al. / Tetrahedron: Asymmetry 15 (2004) 47–52
19. Li, K.; Zhou, Z.; Wang, L.; Chen, Q.; Zhao, G.; Zhou, Q.;
Tang, C. Tetrahedron: Asymmetry 2003, 14, 95–100.
20. Basavaiah, D.; Jayapal Reddy, G.; Chandrashekar, V.
Tetrahedron: Asymmetry 2001, 12, 685–689.
21. Basavaiah, D.; Jayapal Reddy, G.; Chandrashekar, V.
Tetrahedron: Asymmetry 2002, 13, 1125–1128.
22. Gamble, M. P.; Simith, A. R. C.; Wills, M. J. Org. Chem.
1998, 63, 6068–6071.
23. Chiodi, O.; Fotiadu, F.; Sylvestre, M.; Buono, G. Tetra-
hedron Lett. 1996, 37, 39–42.
24. Imuta, M.; Kawai, K. I.; Ziffer, H. J. Org. Chem. 1980, 45,
3352–3355.
have briefly compared our results with that of catalysts A
(Wills),22 B, and C (Buono).18;23 The Wills catalyst A shows
better enantioselectivities than our catalyst 1. The Buono
catalyst B offers better enantioselectivities in some cases
than our catalyst 1 while our catalyst 1 shows better
enantioselectivities than B in certain cases. However, the
catalyst C and our catalyst 1 provide similar enantioselec-
tivities. The Corey chemzyme D31 offers better enantio-
selectivities than all these catalysts.
30. The reduction of acetophenone with BH3ÆSMe2 in the
presence of (S)-2-anilinomethylpyrrolidine (10mol %) pro-
vided (R)-1-phenylethanol in 14% enantiomeric purity.
Asami, M.; Sato, S.; Watanabe, H. Chem. Lett. 2000, 990–
991.
25. Hiratake, J.; Inagaki, M.; Nishioka, T.; Oda, J. J. Org.
Chem. 1988, 53, 6130–6133.
26. Prasad, K. R. K.; Joshi, N. N. Tetrahedron: Asymmetry
1996, 7, 3147–3152.
31. Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C. P.;
Singh, V. K. J. Am. Chem. Soc. 1987, 109, 7925–7926.
27. Noyori, R.; Tomino, I.; Tanimoto, Y.; Nishizawa, M.
J. Am. Chem. Soc. 1984, 106, 6709–6716.
28. Theisen, P. D.; Heathcock, C. H. J. Org. Chem. 1988, 53,
2374–2378.
29. With a view to have a quick understanding of the influence
of proximal hydroxyl group on the enantioselectivities, we
H
Ph
N
P
Ph
Ph
MeO
O
PhHP
Ph
OH
O
P
O
O
P
O
N
OH
N
O
N
N
O
Ph
Ph
B
HO
CH3
MeO
C
D
A
B