Direct asymmetric aldol reaction catalyzed by nanocrystalline magnesium oxide

Article abstract of DOI:10.1016/j.tet.2006.07.091

Nanomaterials with their three-dimensional structure and defined size and shape are considered to be suitable candidates for proper alignment with prochiral substrates for unidirectional introduction of reacting species to induce an asymmetric centre. The

Full text of DOI:10.1016/j.tet.2006.07.091

Tetrahedron 62 (2006) 9571–9576
Direct asymmetric aldol reaction catalyzed by nanocrystalline
magnesium oxide
a,*
b
B. M. Choudary, Lakkoju Chakrapani, Thekkathu Ramani, K. Vijay Kumar
b
b
b,
*
and M. Lakshmi Kantam
a
Ogene Systems (I) Pvt. Ltd, 11-6-56, GSR Estates, Moosapet, Hyderabad, India
b
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 15 April 2006; revised 7 July 2006; accepted 27 July 2006
Available online 17 August 2006
Abstract—Nanomaterials with their three-dimensional structure and defined size and shape are considered to be suitable candidates for
proper alignment with prochiral substrates for unidirectional introduction of reacting species to induce an asymmetric centre. The reusable
and suitably aligned nanocrystalline magnesium oxide catalyzed direct asymmetric aldol reaction afforded the chiral b-hydroxy carbonyl
compounds in good yields and moderate ee’s.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
enantioselectivities (ee’s) were accomplished by using di-
nuclear transition metal catalysts by Trost et al., Barbas III
et al. reported the direct asymmetric aldol reactions cata-
lyzed by aldolase enzymes and antibodies. List, Barbas
and their co-workers have explored the asymmetric aldol
reactions with excellent enantioselectivity by using L-pro-
5
6
The aldol reaction is considered to be one of the most impor-
tant carbon–carbon bond forming reactions in both the
biochemical and chemical domains. The aldol reaction is
ubiquitous in synthetic organic chemistry to generate the
elegant intermediates of anti-hypertensive drugs and calcium
7
8
line and its structural analogues for a-branched aliphatic
aldehydes. Only fair ee’s were observed for the reaction of
1
antagonists. Chiral b-hydroxy carbonyl compounds can
6
,9
be readily converted to 1,3-syn- and anti-diols and amino
alcohols, which are the building blocks in many natural
products such as antibiotics, pheromones and in many bio-
logically active compounds. The aldol products have
been successfully converted to key synthetic intermediates
of epithilone A and bryostatin 7.
aromatic aldehydes with acetone either by L-proline or
its derivatives and its structural analogues with the excep-
tion of N-substituted L-prolinamide derivatives. L-Prolin-
amide derivatives from b-amino alcohols gave high ee’s for
1
0
1
1
1
b
11
p-substituted benzaldehydes. In the area of heterogenized
catalysts, solid supported proline-terminated peptides and
benzylpencillin derivatives in conjunction with proline
grafted into mesoporous MCM-41 provide moderate ee’s
1
c
The direct aldol reaction, starting from an aldehyde and an
unmodified ketone, is highly atom efficient compared
with the process in which the preconversion of a ketone
moiety to a more reactive species such as an enol silyl ether,
enol methyl ether or ketone silyl acetal as the aldol donor
2
12
for the direct asymmetric aldol reaction. L-Proline in ionic
liquids and silica supported ionic liquids also provided
moderate enantioselectivity.
1
3
3
(
Mukaiyama aldol reaction) takes place.
A breakthrough in the asymmetric aldol reaction is achieved
with the introduction of in situ prepared heterobimetallic
catalysts, composed of both Lewis acidic sites and Lewis/
Shibasaki et al. achieved the first catalytic asymmetric aldol
reaction between aldehydes and unmodified ketones by
using heterobimetallic multifunctional catalysts. Later,
the direct asymmetric aldol reactions with good to excellent
2
,14
Bronsted basic sites.
explored the asymmetric direct enolate–electrophile reac-
Evans et al. and other groups have
1
c,4
1
5
tions catalyzed by Mg and its derived complexes. Transi-
tion metal chiral complexes, single-site catalysts with a
defined shape and stereochemistry, induce, in general, higher
enantioselectivity in asymmetric synthesis since they permit
unidirectional introduction of the reacting species onto a pro-
chiral substrate in the three-dimensional space to generate
the asymmetric centre. Conversely, heterogeneous catalysts
Keywords: Direct asymmetric aldol reaction; NAP-MgO; Enantiomeric
excess; b-Hydroxy carbonyl compounds.
Corresponding authors. Tel./fax: +91 40 2377 5566 (B.M.C.); tel.: +91 40
719 3510; fax: +91 40 2716 0921 (M.L.K.); e-mail addresses:
bmchoudary@gmail.com; mlakshmi@iict.res.in
*
2
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.091

9572
B. M. Choudary et al. / Tetrahedron 62 (2006) 9571–9576
are not as effective as transition metal chiral complexes due
to their multisite active sites resulting from assorted crystal
structures with different shapes and sizes and also their steric
restrictions. Hence, creation of desired stereochemistry with
defined shape and size in heterogeneous catalysts to build
the asymmetric centre is a challenging problem.
Table 2. Effect of ligand on asymmetric aldol reaction between p-nitro-
benzaldehyde and acetone catalyzed by NAP-MgO at room temperature
a
Entry Ligand
Time Yield ee c
b
(h)
(%)
(%)
1
2
3
4
5
6
7
8
9
1
(1R,2R)-(+)-1,2-Diphenylethylenediamine 24
(1R,2R)-(ꢀ)-1,2-Diaminocyclohexane 24
(1S,2S)-(+)-1,2-Diphenylethylenediamine 24
75
75
75
75
75
75
75
60
60
75
15
12
16
25
0
0
0
0
0
1
6
(1S,2S)-(+)-1,2-Diaminocyclohexane
0
24
24
24
24
24
24
24
Nanocrystalline metal oxides with their three-dimensional
structure and defined size and shape are considered to be
suitable candidates for proper alignment with prochiral sub-
strates for unidirectional introduction of reacting species to
induce an asymmetric centre. Recently, our group evolved
the single-site nanocrystalline magnesium oxide (MgO)
for the synthesis of chiral epoxy ketones, chiral nitro alco-
0
(S)-(ꢀ)-1,1 -Binaphthyl-2,2 -diamine
0
0
(R)-(ꢀ)-1,1 -Binaphthyl-2,2 -diamine
(+)-Diethyl-L-tartrate
(S)-(ꢀ)-Binol
(R)-(ꢀ)-Binol
0
(ꢀ)-Diethyl-L-tartrate
0
a
Conditions: aldehyde (1.0 mmol), acetone (13.7 mmol), NAP-MgO
(0.100 g), dry THF (2 mL). In all cases 20 mol % of ligand was used.
Isolated yields.
1
7
hols and Michael adducts.
b
c
The ee% was determined by HPLC analysis using a chiral column
(
We herein report the direct asymmetric aldol reaction of
aldehydes and ketones catalyzed by nanocrystalline magne-
sium oxide (MgO) to afford the optically active b-hydroxy
carbonyl compounds in good yields and moderate ee’s.
chiralpak AS-H, AD-RH).
Table 3. Asymmetric aldol reaction between p-nitrobenzaldehyde and ace-
tone with different solvents by using (1S,2S)-(+)-1,2-diaminocyclohexane
as chiral ligand at room temperature
a
b
c
Entry
Solvent
Time (h)
Yield (%)
ee (%)
2
. Results and discussions
1
2
3
4
5
THF
DMF
DMSO
24
24
24
24
24
75
62
60
5
17
0
0
0
0
1
6
Various magnesium oxide crystals [commercial MgO, CM-
MgO (SSA: 30 m /g), conventionally prepared MgO, NA-
2
CHCl
DCM
3
2
MgO (SSA: 250 m /g) and aerogel-prepared MgO, NAP-MgO
(
5
2
SSA: 590 m /g)] were initially screened in the achiral
a
Conditions: aldehyde (1.0 mmol), acetone (13.7 mmol), (1S,2S)-(+)-1,2-
diaminocyclohexane (20 mol %), NAP-MgO (0.100 g), dry THF (2 mL).
Isolated yields.
The ee% was determined by HPLC analysis using a chiral column
chiralpak AS-H, AD-RH).
aldol reaction between p-nitrobenzaldehyde and acetone
at room temperature. Based on the results of the achiral aldol
reaction, we carried out direct asymmetric aldol reaction.
b
c
(
In the process of optimization of the reaction conditions, we
explored different samples of MgO and NAP-MgO was
found to be superior to others (Table 1). We have screened
different chiral auxiliaries for the asymmetric aldol reaction
between p-nitrobenzaldehyde and acetone catalyzed by
NAP-MgO as specified in Table 2 and optimum ee was
obtained with (1S,2S)-(+)-1,2-diaminocyclohexane.
NAP-MgO was tested in the direct asymmetric aldol reac-
tion of various substituted aromatic aldehydes (Table 4).
When benzaldehydes were substituted at the 4-position
with electron-withdrawing (EW) groups or electron-donating
(ED) groups, higher ee’s were observed when compared
with the corresponding 2-substituted benzaldehydes with
either EWor ED groups, which may be ascribed to the steric
hindrance for the unidirectional entry of reacting species.
(1S,2S)-(+)-1,2-Diaminocyclohexane (20 mol %) was used
as the chiral auxiliary with respect to the aldehyde.
To understand the relation between the structure and reactiv-
ity in the direct asymmetric aldol reaction, it is better to
know the structure and nature of the reactive species of
the catalyst. NAP-MgO has a three-dimensional structure,
which, having high surface concentrations of edge/corner
and various exposed crystal planes (such as 002, 001 and
Later, we explored the activity of NAP-MgO with different
solvents at different temperatures (Table 3). As the temper-
ature decreases, enantioselectivity increases with decrease
in rate of reaction. The solvent THF and a temperature
ꢁ
ꢀ
20 C showed optimum enantioselectivity.
1
11), leads to inherently high surface reactivity per unit
To evaluate the importance of our catalytic system, we
have carried out the aldol reaction with (1S,2S)-(+)-1,2-
diaminocyclohexane (20 mol %), 1 mmol of aldehyde and
1 mL of acetone in the absence of NAP-MgO at room tem-
perature. No aldol adduct was formed.
area. Thus, NAP-MgO indeed displayed the highest activity
compared to that of NA-MgO and CM-MgO. Besides this,
the NAP-MgO has a Lewis acid site Mg , Lewis basic sites
2
+
2
ꢀ ꢀ
and O , lattice bound and isolated Bronsted hydroxyls
and anionic and cationic vacancies.
O
1
6
The aldol reaction was known to be driven by base catalysts
and accordingly, the surface –OH and O of these magne-
sium oxide crystals are expected to trigger this reaction.
Table 1. Achiral aldol reaction between p-nitrobenzaldehyde and acetone at
room temperature catalyzed by different crystallites of MgO
a
2ꢀ
Entry
Catalyst
Solvent
Time (h)
Conversion (%)
1
2
3
NAP-MgO
CP-MgO
CM-MgO
THF
THF
THF
24
36
36
75
10
0
The NAP-MgO was reused after heating the catalyst at
ꢁ
2
50 C for 1 h under nitrogen atmosphere. Thus the catalyst
was reused for four times, which showed consistent yields
and ee’s.
a
Conditions: catalyst (100 mg), aldehyde (1 mmol), acetone (13.7 mmol).

B. M. Choudary et al. / Tetrahedron 62 (2006) 9571–9576
9573
a
Table 4. Direct asymmetric aldol reaction of aldehydes and acetone with NAP-MgO
O
C
OH
O
C
C
H
NAP-MgO, dry THF, -20 °C
CH3
R
CH2
R-CHO
+
(
1S,2S)-(+)-1,2-diaminocyclohexane
H C
CH3
3
1
1 samples
1
5-60% ee
b
c
Entry
1
Aldehyde
Time (h)
24
Yield (%)
ee (%)
60
CHO
70
F
CHO
2
3
4
24
24
24
65
67
48
40
40
Cl
Br
CHO
CHO
60
CN
CHO
d
75, 72, 0
e
e
5
6
24
24
53, 53
O2N
CHO
70
15
NO2
CHO
7
24
70
27
NO2
Cl
8
9
24
36
55
60
33
23
CHO
CHO
CHO
1
1
0
1
36
24
50
75
17
43
H3C
CHO
N
a
b
c
d
e
All reactions were performed on 1 mmol substrate in 1 mL (13.7 mmol) acetone using 100 mg of NAP-MgO.
Yield of the product after isolation by column chromatography.
The ee% was determined by HPLC analysis using a chiral column (chiralpak AS-H, AD-RH).
Fifth cycle.
Without catalyst.
3. Conclusion
4. Experimental
In conclusion, the NAP-MgO is an active, reusable catalyst
for the production of chiral b-hydroxy carbonyl compounds
through direct asymmetric aldol reaction. Thus nanocrystal-
line MgO with its definite shape, size and accessible –OH
groups and higher density of Mg at the edges/corner shows
higher activity in the direct asymmetric aldol reaction.
4.1. General
All chemicals were purchased from Aldrich and were used as
received. All solvents were of analytical grade from Merck
India Pvt. Ltd and used as such. All reactions were conducted
under nitrogen atmosphere at ꢀ20 C in THF. The H NMR
2
+
ꢁ
1

9574
B. M. Choudary et al. / Tetrahedron 62 (2006) 9571–9576
spectra of samples were recorded on a Varian-Unity
00 MHz and Bruker-Avance-300 MHz spectrometer using
TMS as an internal standard in CDCl . High Performance
by HPLC analysis using chiralcel AS-H column (isopropyl
alcohol/hexane 10:90), UV 254 nm, flow rate 1.0 mL/min;
major isomer, t 14.8 min and minor isomer, t 20.1 min.
4
3
R
R
Liquid Chromatography (HPLC) was performed using
AGILENT-1100 series liquid chromatograph equipped with
a single pump and UV detector (fixed at 216 nm) using chiral-
cel AS-H column with isopropanol/hexane as eluting agent.
Optical rotations were obtained on an automated JASCO
0
(2c). Yield, 67% (156 mg); colourless oil, H NMR
4.2.3. (4R)-Hydroxy-4-(4 -bromophenyl)-butan-2-one
1
(CDCl ): d 7.47 (d, J¼8.4 Hz, 2H, Ar-H), 7.22 (d, J¼
3
8.4 Hz, 2H, Ar-H), 5.08 (dd, J¼5.6, 7.8 Hz, 1H, –CHOH),
P-1020 polarimeter, and the values were reported in absolute
rotations: [a]D
3.38 (br s, 1H, –OH), 2.80–2.70 (m, 2H, –CH CO), 2.20 (s,
2
temperature
[concentration c g/100 mL of sol-
3H, –COCH ); IR (neat): 3427, 2913, 1703, 1438, 1369,
3
ꢀ
1
+
vent]. The absolute stereochemistry was assigned as (R) by
comparison of the optical rotation with the literature values.
For energy calibration, we have used the carbon 1s photo-
electron line. The carbon 1s binding energy was taken to
be 285.0 eV. Spectra were deconvoluted using the Sun
Solaris based vision 2 curve resolver. The location and the
full width at half maximum (FWHM) for a species were first
determined by using the spectrum of a pure sample.
1071, 546 cm ; Mass (EI): m/z 243 (M ), 43; HRMS
(ESI-MS) (ꢀve): exact mass calcd for (MꢀHꢀH O):
2
222.9759. Found: 222.9768; enantiomeric excess: 40%,
which was determined by HPLC analysis using chiralcel
AS-H column (isopropyl alcohol/hexane 15:85), UV
262 nm, flow rate 1.0 mL/min; major isomer, t 14.5 min
R
and minor isomer, t 19.8 min.
R
0
(2d). Yield, 60% (113 mg); pale yellow viscous oil, H
4
.2.4. (4R)-Hydroxy-4-(4 -cyanophenyl)-butan-2-one
1
4
.2. General procedure for the aldol reaction
NMR (CDCl ): d 7.64 (d, J¼8.1 Hz, 2H, Ar-H), 7.47 (d,
3
A mixture of acetone (1 mL, 13.7 mmol), (1S,2S)-(+)-1,2-
diaminocyclohexane (20 mol %, 22.8 mg) and catalyst
J¼8.1 Hz, 2H, Ar-H), 5.20 (m, 1H, –CHOH), 3.32 (br s,
1H, –OH), 2.82 (m, 2H, –CH CO), 2.21 (s, 3H, –COCH );
3
2
ꢀ1
(
100 mg) was introduced into a 25 mL round bottomed flask
IR (neat): 3418, 2934, 1713, 1489, 1369, 1077, 538 cm
;
ꢁ
+
containing dry THF (2 mL) at ꢀ20 C and stirred for 30 min
under nitrogen atmosphere. To the reaction mixture, alde-
hyde (1 mmol) was added at that temperature and stirring
was continued. After completion of the reaction (monitored
by TLC), the reaction mixture was centrifuged to separate
the catalyst and washed several times with THF. The com-
bined organic layers were dried over Na SO and the solvent
Mass (EI): m/z 189 (M ), 43; HRMS (ESI-MS) (ꢀve): exact
mass calcd for (MꢀHꢀH O): 170.0606. Found: 170.0600;
2
enantiomeric excess: 30%, which was determined by
HPLC analysis using chiralcel AS-H column (isopropyl
alcohol/hexane 30:70), UV 254 nm, flow rate 1.0 mL/min;
major isomer, t 10.6 min and minor isomer, t 19.8 min.
R
R
2
4
0
Yield, 75% (156 mg); pale brown viscous oil, H NMR
was removed under reduced pressure. After purification by
column chromatography on silica gel using 10% ethyl ace-
tate in petroleum ether, the aldol adduct was obtained.
4.2.5. (4R)-Hydroxy-4-(4 -nitrophenyl)-butan-2-one (2e).
1
(CDCl ): d 8.20 (d, J¼7.0 Hz, 2H, Ar-H), 7.52 (d, J¼
3
7
.0 Hz, 2H, Ar-H), 5.30–5.20 (m, 1H, –CHOH), 3.56 (br s,
The chiral auxiliary (1S,2S)-(+)-1,2-diaminocyclohexane
can be recovered quantitatively with no observable change
in enantiomeric purity from the same chromatographic
column by increasing the proportion of ethyl acetate in the
eluent.
1H, OH), 2.85–2.80 (m, 2H, –CH CO), 2.21 (s, 3H,
2
–COCH ); Mass (EI): m/z 209 (M ), 43; HRMS (ESI): exact
3
+
6
mass calcd for C H NO : 209.06809. Found: 232.1411
1
0
11
4
+
(M+Na) ; IR (neat): 3419, 2930, 1716, 1514, 1480,
ꢀ
1
1370 cm ; enantiomeric excess: 53%, which was deter-
mined by HPLC analysis using chiralcel AS-H column
(isopropyl alcohol/hexane 15:85), UV 254 nm, flow rate
0
2a). Yield, 70% (127 mg); colourless oil, H NMR
4
.2.1. (4R)-Hydroxy-4-(4 -fluorophenyl)-butan-2-one
1
(
1.0 mL/min; major isomer, t 14.2 min and minor isomer,
R
(
CDCl ): d 7.38 (d, J¼8.0 Hz, 2H, Ar-H), 7.09 (d,
tR 20.3 min.
3
J¼8.0 Hz, 2H, Ar-H), 5.16 (dd, J¼4.6, 6.6 Hz, 1H,
0
Yield, 70% (146 mg); pale brown viscous oil, H NMR
–
2
1
(
1
CHOH), 3.35 (br s, 1H, –OH), 2.87 (m, 2H, –CH CO),
2
4.2.6. (4R)-Hydroxy-4-(2 -nitrophenyl)-butan-2-one (2f).
1
.23 (s, 3H, –COCH ); IR (neat): 3445, 2925, 1713, 1509,
3
+
377; Mass (EI): m/z 182 (M ), 43; HRMS (ESI-MS)
(CDCl ): d 7.96 (dd, J¼1.2, 8.1 Hz, 1H, Ar-H), 7.91 (dd,
3
ꢀve): exact mass calcd for (MꢀHꢀH O): 163.0559. Found:
J¼1.2, 8.1 Hz, 1H, Ar-H), 7.71 (dt, J¼1.2, 8.1 Hz, 1H, Ar-
H), 7.44 (dt, J¼1.2, 8.1 Hz, 1H, Ar-H), 5.70 (dd, J¼9.3 Hz,
1H, –CHOH), 3.76–3.70 (br s, 1H, OH), 2.70–2.85 (m, 2H,
–CH CO), 2.24 (s, 3H, –COCH ); Mass (EI): m/z 209
2
63.0559; enantiomeric excess: 60%, which was determined
by HPLC analysis using chiralcel AS-H column (isopropyl
alcohol/hexane 20:80), UV 257 nm, flow rate 1.0 mL/min;
major isomer, t 8.9 min and minor isomer, t 11.2 min.
2
3
+
ꢀ1
(M ), 43; IR (neat): 3416, 2934, 1719, 1512, 1376 cm
;
R
R
enantiomeric excess: 15%, which was determined by
HPLC analysis using chiralcel AS-H column (isopropyl alco-
hol/hexane 30:70), UV 254 nm, flow rate 1.0 mL/min; major
isomer, t 10.4 min and minor isomer, t 13.1 min.
0
.2.2. (4R)-Hydroxy-4-(4 -chlorophenyl)-butan-2-one
2b). Yield, 65% (128 mg); colourless oil, H NMR
4
(
1
(
CDCl ): d 7.36 (d, J¼8.2 Hz, 2H, Ar-H), 7.20 (d, J¼
3
R
R
8
3
–
5
.2 Hz, 2H, Ar-H), 5.10 (dd, J¼5.0, 7.0 Hz, 1H, –CHOH),
0
Yield, 70% (146 mg); yellow viscous oil, H NMR (CDCl ):
.55 (br s, 1H, –OH), 2.67 (m, 2H, –CH CO), 2.10 (s, 3H,
2
4.2.7. (4R)-Hydroxy-4-(3 -nitrophenyl)-butan-2-one (2g).
1
COCH ); IR (neat): 3433, 2924, 1709, 1463, 1370, 1079,
3
3
ꢀ1
+
67 cm ; Mass (EI): m/z 179 (M ), 43; HRMS (ESI-MS)
d 8.24 (s, 1H, Ar-H), 8.13 (d, J¼8.6 Hz, 1H, Ar-H), 7.71 (d,
J¼7.5 Hz, 1H, Ar-H), 7.53 (t, J¼7.5 Hz, 1H, Ar-H), 5.27–
5.15 (m, 1H, –CHOH), 3.50 (br s, 1H, OH), 2.82 (m, 2H,
(
1
ꢀve): exact mass calcd for (MꢀHꢀH O): 179.0264. Found:
2
79.0265; enantiomeric excess: 48%, which was determined

B. M. Choudary et al. / Tetrahedron 62 (2006) 9571–9576
9575
–
1
CH CO), 2.23 (s, 3H, –COCH ); IR (neat): 3414, 2931,
2
715, 1519, 1370 cm ; Mass (EI): m/z 209 (M ), 43; enan-
were obtained from Nano Scale Materials Inc., Manhattan,
Kansas, USA.
3
ꢀ
1
+
tiomeric excess: 27%, which was determined by HPLC anal-
ysis using chiralcel AS-H column (isopropyl alcohol/hexane
2
1
0:80), UV 254 nm, flow rate 1.0 mL/min; major isomer, tR
1.1 min and minor isomer, t 15.0 min.
References and notes
R
1
. (a) Marciniak, G.; Delgado, A.; Velly, J.; Leclerc, G.; Decker,
N.; Schwartz, J. J. Med. Chem. 1989, 32, 1402; (b) Enders,
D.; Muller, S.; Demir, A. S. Tetrahedron Lett. 1988, 29,
6437; (c) Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai,
H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
0
2h). Colourless oil, H NMR (CDCl ): d 7.60 (d,
4
(
.2.8. (4R)-Hydroxy-4-(2 -chlorophenyl)-butan-2-one
1
3
J¼8.6 Hz, 1H, Ar-H), 7.34–7.14 (m, 3H, Ar-H), 5.46 (m,
J¼10.4 Hz, 1H, –CHOH), 3.58 (br s, 1H, –OH), 2.90–3.05
(
2
4
m, 2H, –CH CO), 2.22 (s, 3H, –COCH ); IR (neat): 3410,
2
930, 1712, 1440, 840 cm ; Mass (EI): m/z 179 (M ),
3; enantiomeric excess: 33%, which was determined by
2. (a) Trost, B. M. Science 1991, 254, 1471; (b) Trost, B. M.
Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
3. (a) Palomo, C.; Oiarbide, M.; Garcia, J. Chem. Soc. Rev. 2004,
33, 65; (b) Machajewski, T. D.; Wong, C.-H. Angew. Chem.,
Int. Ed. 2000, 39, 1352.
3
ꢀ
1
+
HPLC analysis using chiralcel AS-H column (isopropyl
alcohol/hexane 8:92), UV 262 nm, flow rate 1.0 mL/min;
major isomer, t 18.2 min and minor isomer, t 20.1 min.
4. Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki,
M. Angew. Chem., Int. Ed. 1997, 36, 1871.
R
R
4
6
7
.2.9. (4R)-Hydroxy-4-phenyl-butan-2-one (2i). Yield,
0% (98 mg); colourless oil, H NMR (CDCl ): d 7.33–
.17 (m, 5H, Ar-H), 5.15–5.04 (m, 1H, –CHOH), 3.17 (br
5. (a) Trost, B. M.; Ito, H. J. Am. Chem. Soc. 2000, 122, 12003; (b)
Trost, B. M.; Ito, H.; Silcoff, E. R. J. Am. Chem. Soc. 2001, 123,
3367; (c) Evans, D. A.; Downey, C. W.; Hubbs, J. L. J. Am.
Chem. Soc. 2003, 125, 8706.
6. Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem.
Soc. 2001, 123, 5260 and the references therein.
7. (a) Casas, J.; Engqvist, M.; Ibrahem, I.; Kaynak, B.; Cordova,
A. Angew. Chem., Int. Ed. 2005, 44, 1343; (b) Northrup, A. B.;
Mangion, I. K.; Hettche, F.; MacMillan, D. W. C. Angew.
Chem., Int. Ed. 2004, 43, 2152; (c) Pidathala, C.; Hoang, L.;
Vognola, N.; List, B. Angew. Chem., Int. Ed. 2003, 42, 2785;
1
3
s, 1H, –OH), 2.80–2.75 (m, 2H, –CH CO), 2.17 (s, 3H,
2
–
Mass (EI): m/z 164 (M ), 43; HRMS (EI): exact mass calcd
for C H O : 164.0833. Found: 164.0837 (M ); enan-
1
tiomeric excess: 23%, which was determined by HPLC anal-
ysis using chiralcel AS-H column (isopropyl alcohol/hexane
ꢀ
1
COCH ); IR (neat): 3413, 2932, 1718, 1450, 890 cm
;
3
+
13a
+
0 12 2
20:80), UV 254 nm, flow rate 1.0 mL/min; major isomer, tR
16.0 min and minor isomer, t 19.2 min.
R
(
d) List, B. Tetrahedron 2002, 58, 5573; (e) List, B. Acc.
0
2j). Yield, 50% (89 mg); colourless oil, H NMR (CDCl ):
4
(
.2.10. (4R)-Hydroxy-4-(4 -methylphenyl)-butan-2-one
Chem. Res. 2004, 37, 548; (f) Notz, W.; Tanaka, F.; Barbas,
C. F., III. Acc. Chem. Res. 2004, 37, 580.
1
3
d 7.26 (d, J¼7.8 Hz, 2H, Ar-H), 7.17 (d, J¼7.8 Hz, 2H, Ar-
8. (a) Hartikka, A.; Arvidsson, P. I. Tetrahedron: Asymmetry
2004, 15, 1831; (b) Torii, H.; Nakadai, M.; Ishihara, K.;
Saito, S.; Yamamoto, H. Angew. Chem., Int. Ed. 2004, 43,
1983.
9. List, B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc.
2000, 122, 2395.
10. (a) Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37, 570; (b)
Kofoed, J.; Nielsen, J.; Reymond, J.-L. Bioorg. Med. Chem.
Lett. 2003, 13, 2445.
11. (a) Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.;
Jiang, Y.-Z.; Wu, Y.-D. J. Am. Chem. Soc. 2003, 125,
5262; (b) Tang, Z.; Yang, Z.-H.; Chen, X. H.; Cun, L. F.;
Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. J. Am. Chem. Soc.
2005, 127, 9285.
H), 5.25 (m, 1H, –CHOH), 3.32 (br s, 1H, –OH), 2.77–2.88
(
–
m, 2H, –CH CO), 2.35 (s, 3H, –CH ), 2.20 (s, 3H,
2 3
ꢀ
COCH ); IR (neat): 3423, 2925, 1710, 1464, 808 cm ;
3
1
+
Mass (EI): m/z 178 (M ), 43; HRMS (EI): exact mass calcd
for C H O : 178.09938. Found: 160.08882 (MꢀHꢀH O);
1
1
14
2
2
enantiomeric excess: 17%, which was determined by HPLC
analysis using chiralcel AS-H column (isopropyl alcohol/
hexane 15:85), UV 257 nm, flow rate 1.0 mL/min; major iso-
mer, t 9.4 min and minor isomer, t 11.2 min.
R
R
0
5% (124 mg); white solid, H NMR (CDCl ): 8.50–8.53
4
7
.2.11. 4-Hydroxy-4-(2 -pyridyl)-butan-2-one (2k). Yield,
1
3
(
1
(
–
1
m, 1H, PyH), 7.71 (dt, 1H, J¼7.9, 1.7 Hz, PyH), 7.45 (d,
H, J¼7.9, 1.7 Hz, PyH), 7.16–7.23 (m, 1H, PyH), 5.19
12. (a) Andreae, M. R. M.; Davis, A. P. Tetrahedron: Asymmetry
2005, 16, 2487; (b) Dhar, D.; Beadham, I.; Chandrasekaran,
S. Proc. Indian Acad. Sci. Chem. Sci. 2003, 115, 365.
13. (a) Loh, T.-P.; Feng, L.-C.; Yang, H.-Y.; Yang, J.-Y.
Tetrahedron Lett. 2002, 43, 8741; (b) Chandrasekhar, S.;
Narsimhulu, Ch.; Ramakrishna, N.; Sultana, S. Tetrahedron
Lett. 2004, 45, 4581; (c) Gruttadauria, M.; Riela, S.; Meo,
dd, 1H, J¼8.2, 3.9 Hz, –CHOH), 2.90–3.06 (m, 2H,
CH CO), 2.21 (s, 3H, –COCH ); IR (neat): 3133, 1718,
2 3
ꢀ
1
+
595 cm ; Mass (EI): m/z 166 (M+1) , 43; HRMS (ESI-
MS) (+ve): exact mass calcd for (M+H): 166.0868. Found:
66.0856; enantiomeric excess: 43%, which was determined
1
by HPLC analysis using chiralcel OJ-H column (isopropyl
alcohol/hexane 1:3), UV 206 nm, flow rate 1.0 mL/min;
major isomer, t 19.5 min and minor isomer, t 21.5 min.
0
Lo; Francesca D Anna, P.; Noto, R. Tetrahedron Lett. 2004,
45, 6113.
R
R
1
4. For reviews, see: Shibasaki, M.; Sasai, H.; Arai, T. Angew.
Chem., Int. Ed. 1997, 36, 1236.
Acknowledgements
15. (a) Evans, D. A.; Nelson, S. G. J. Am. Chem. Soc. 1997, 119,
452; (b) Barnes, D. M.; Zhang, J.; Morton, H. E.; King,
6
We wish to thank the CSIR for financial support under the
Task Force Project CMM-0005. L.C. and T.R. thank the
Council of Scientific and Industrial Research, India, for
the award of fellowship. Nanocrystalline MgO catalysts
S. A.; Ji, J. J. Am. Chem. Soc. 1999, 121, 10215; (c) Willis,
M. C.; Cutting, G. A.; Piccio, V. J.-D.; Durbin, M. J.; John,
M. P. Angew. Chem., Int. Ed. 2005, 44, 1543; (d) Evans,
D. A.; Tedrow, J. S.; Shaw, J. T.; Downey, C. W. J. Am.

9
576
B. M. Choudary et al. / Tetrahedron 62 (2006) 9571–9576
Jiang, Y.; Lagadic, I.; Zhang, D. J. Phys. Chem. 1996, 100,
12142.
Chem. Soc. 2002, 124, 392; (e) Evans, D. A.; Tedrow, J. S.;
Shaw, J. T.; Downey, C. W. Org. Lett. 2002, 4, 1127.
6. (a) Jeevanandam, P.; Klabunde, K. J. Langmuir 2002, 18, 5309;
b) Richards, R.; Li, W.; Decker, S. C.; Zaikovski; Volodin, A.;
Rieker, T.; Klabunde, K. J. J. Am. Chem. Soc. 2000, 122, 4921;
c) Klabunde, K. J.; Stark, J.; Mohs, C.; Park, D. G.; Decker, S.;
1
17. (a) Choudary, B. M.; Kantam, M. L.; Ranganath, K. V. S.;
Mahendar, K.; Sreedhar, B. J. Am. Chem. Soc. 2004, 126,
3396; (b) Choudary, B. M.; Ranganath, K. V. S.; Pal, U.;
Kantam, M. L.;Sreedhar, B.J. Am. Chem. Soc. 2005, 127, 13167.
(
(