Asymmetric Michael addition reactions using a chiral La-Na aminodiolate catalyst

Article abstract of DOI:10.1016/S0957-4166(02)00240-9

(R,R)-(+)-2-[Benzyl-(2-hydroxy-2-phenylethyl)amino]-1-phenylethanol 1 is used as a chiral ligand in the synthesis of an optically active lanthanum-sodium amino diol complex LS-1. This heterobimetallic catalyst is quite effective as an asymmetric catalyst for various Michael addition reactions, ¹H NMR study indicates the co-ordination of enone to the central lanthanum atom in LS-1. The reaction conditions were optimized and the adducts were obtained in high yield with moderate to high enantiomeric excess under extremely mild conditions.

Full text of DOI:10.1016/S0957-4166(02)00240-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1053–1058
Asymmetric Michael addition reactions using a chiral La–Na
aminodiolate catalyst
N. Prabagaran and G. Sundararajan*
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
Received 9 April 2002; accepted 13 May 2002
Abstract—(R,R)-(+)-2-[Benzyl-(2-hydroxy-2-phenylethyl)amino]-1-phenylethanol 1 is used as a chiral ligand in the synthesis of an
optically active lanthanum–sodium amino diol complex LS-1. This heterobimetallic catalyst is quite effective as an asymmetric
1
catalyst for various Michael addition reactions, H NMR study indicates the co-ordination of enone to the central lanthanum
atom in LS-1. The reaction conditions were optimized and the adducts were obtained in high yield with moderate to high
enantiomeric excess under extremely mild conditions. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
lithium–aluminum complex. Herein, we discuss the syn-
thesis and catalytic applications of the lanthanum–
sodium aminodiol–heterobimetallic complex for
asymmetric Michael addition reactions.
Preparation of synthetic enzymes (chemzymes)1 remains
an interesting and challenging goal in the field of
supramolecular chemistry. Considerable new work con-
cerning reactions mediated by heterobimetallic com-
plexes has been reported.2 The use of chiral
heterobimetallic complexes is now common in Michael
addition,3 nitroaldol,4 hydrophosphorylation,5 epoxide
ring opening,6 epoxidation of a,b-unsaturated ketones,7
Diels–Alder,8 and nitro-Mannich9 reactions. The heter-
obimetallic complex, which contains an early and a late
transition metal showed some interesting properties
such as multifunctionality,10 that is to have both acidic
and basic centers in the same complex. In the complex,
the metal centers possibly ‘communicate’ with one
another, show some cooperative effects11 in the posi-
tioning of the reactants, enhance the reactivity of both
reactants and ultimately increase the stereoselectivity in
product formation.
2. Results and discussion
The heterobimetallic complex was synthesised from lan-
thanum chloride,16 sodiated amino diol Na2-1 and
sodium tert-butoxide.17 The combined analysis of the
product by inductively coupled plasma spectroscopy
(icp) analysis of lanthanum, sodium and the recovered
amount of amino diol showed that the LS-1 complex
consisted of lanthanum, sodium and amino diol in a
ratio of 1:3:3. The single crystal XRD of the ligand 1
was reported earlier18 by our group and a single crystal
XRD study of the catalyst is currently in progress. The
MMX energy-minimized structure of the lanthanum–
sodium amino diol complex LS-1 show the vacant site
at lower axis for substrate coordination. The central
lanthanum ion in the heterobimetallic catalyst is the
origin of Lewis acidity, while the dioxo-sodium moiety
was incorporated as a Bronsted base.19 The basicity of
the catalyst can be estimated by the abstraction of
protons from different substrates (Scheme 1).
The asymmetric Michael reaction which is an important
technique for carbonꢀcarbon and carbon–heteroatom
bond formation has been studied using chiral auxil-
iaries,12 chiral monometallic,13 chiral heterobimetallic14
and chiral crown ether complexes.15 The C2-symmetric
amino diol (R,R)-(+)-2-[benzyl-(2-hydroxy-2-phenyl-
ethyl)amino]-1-phenylethanol 1 has been used previ-
ously by our group for generating a heterobimetallic
To investigate the chiral induction properties of the
complex, the changes in the chemical shift of the C(1)
proton of the amino diol 1 in LS-1 was observed over
time. It was found that the complex was stable for 24
h, but with longer times, the complex decomposed.20
* Corresponding author. Tel.: +0-091-257-8254; fax: +0-091-257-8241;
e-mail: gsundar@iitm.ac.in
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00240-9

1054
N. Prabagaran, G. Sundararajan / Tetrahedron: Asymmetry 13 (2002) 1053–1058
NaH
Ph
H
Ph
H
Ph
H
Ph
Ph
Ph
N
THF, 1h
N
NaO
ONa
N
HO
OH
O
O
Na
O
Na
H
O
LaCl3
NaOtBu
La
Ph
Ph
thf, 45 min
N
N
Ph
O
Ph
O
Na
LS-1
Scheme 1. Synthesis of LS-1.
In the presence of 10 mol% of the catalyst LS-1, the
reaction of p-methyl thiophenol with cyclopentenone
was complete in 20 min in dry THF at −40°C but the ee
was poor. We next investigated the reaction in two
different solvents and found that the use of tolu-
ene:THF (1:1) gave the best result (48% ee) in a short
reaction time (Table 1).
Table 2. Effect of temperature variation in asymmetric
Michael addition reaction
SH
o
O
LS-1, 20 min
Toluene:THF
+
2a
*
SC6H4-p-Me
Temperature(oC): 35, 0, -40
Me
Temperature (°C)
Time (min)
ee (%)
Yield (%)
Table 1. Change of solvents and its effect in asymmetric
Michael addition reaction
35
0
−40
10
15
20
28
42
48
90
90
92
SH
o
O
LS-1
-40oC, solvent
2a
+
*
S-C6H4-p-Me
Me
The results shown in Table 3 indicate that the yield and
enantiomeric excess of the Michael adduct depends not
only on the nature of the catalyst but also on the
Michael acceptors and donors.
solvent : Toluene, THF, Toluene:THF
Solvent
Time (min)
ee (%)
Yield (%)
Toluene:THF
Toluene
THF
20
35
10
48
48
16
92
90
90
Table 3. Asymmetric Michael addition reaction of dialkyl
malonates to cycloalkenones
o
O
LS-1, 20 h
+
3
HNu
Toluene:THF
*
Nu
t
We assume here that in high polarity solvents the
complex dissociates and gives poor enantiomeric
excess.21 In low polar solvents the Michael acceptor and
donor possibly remain part of the ensemble to afford
the product with high enantiomeric excess.
n
n
Nu: -CH(CO2Et)2, -CH(CO2Bn)2, -CH(CO2 Bu)2
Product
Nu
n
Time
(h)
Yield
(%)
ee
(%) (%)
eea
When the temperature was lowered to −40°C, a higher
enantiomeric excess was observed in the product. Possi-
bly, at lower temperatures, the catalyst and the transi-
tion state are more immobilized, leading to enhanced
ee22 (Table 2).
3a
3b
3b
3c
3d
3e
3f
CH2(CO2Et)2
CH2(CO2Et)2
CH2(CO2Et)2
CH2(CO2Bn)2
CH2(CO2Bn)2
1
2
2
1
2
1
2
20
20
20
20
20
20
20
82
85
83
84
86
86
80
78
77
67b
93
95
77
80
86
80
–
83
92
90
94
t
CH2(CO2 Bu)2
t
CH2(CO2 Bu)2
The Michael additions of dialkyl malonates to
cycloalkenones were also performed with the LS-1
complex (Table 3) showing moderate to high enan-
tiomeric excess. However, the ee values are lower when
compared with the chiral induction seen when reactions
are carried out using the lithium–aluminum aminodio-
late Li-Al-1.
a Addition using Li-Al-1.
b Cyclohexenone reacted with LS-1 prepared from lanthanum isopro-
poxide
To examine the activity of the LS-1 complex, cyclo-
hexenone was added at different times to the catalyst

N. Prabagaran, G. Sundararajan / Tetrahedron: Asymmetry 13 (2002) 1053–1058
1055
Table 4. Asymmetric Michael addition of thiophenols to
cycloalkenones
and the changes in the chemical shifts of the a-proton
of cyclohexenone were also followed and it was
observed that the LS-1 complex is active for 24 h and
after that, it decomposed slowly. The changes in the
chemical shifts of the a-proton of cyclohexenone show
that the carbonyl group of the enone is coordinated to
the lanthanum atom in the LS-1 molecule indicating
the Lewis acidity of the complex.
SH
o
O
LS-1, 20 min
R = H, CH3
S-C6H4-p-R
+
2
Toluene:THF
*
n
n
R
Product
R
n
Time
(min)
Yield
(%)
ee
(%)
eea
(%)
Based on these observations, a mechanism, almost
matching Shibasaki’s work on the formation of
Michael adducts, can be proposed where the enone
coordinates with the central metal ion and the donor is
deprotonated by the basic heterobimetallic complex.
The sodium enolate attacks the Michael acceptor and
holds it in a specific position leading to stereoinduction.
After the 1,4-addition, the cyclohexenone is released
from the lanthanum center, abstracting a proton from
the hydroxyl group in the complex to afford the 1,4-
adduct (Scheme 2).
2a
2b
2b
2c
2d
CH3
H
H
CH3
H
1
2
2
2
1
20
20
20
20
20
92
95
90
90
91
48
39
34b
43
54
26
40
–
40
32
a Addition using Li-Al-1.
b Cyclohexenone reacted with LS-1 prepared from lanthanum isopro-
poxide.
Table 5. Asymmetric Michael addition reactions of 2-
methyl cyclopentenone
o
*
4
O
*
SPh
o
*
5
*
CH(COOEt)2
Product
Donor
Time
Yield
(%)
de
(%)
ee
(%)
4
5
PhSH
CH2(CO2Et)2
20 min 90
20 h 86
45
60
47
25
Scheme 2. Proposed mechanism for asymmetric Michael
addition reaction using LS-1.
Asymmetric Michael additions of thiols to
cycloalkenones were also carried out leading to moder-
ate enantiomeric excess but comparatively higher than
the induction caused by the Li-Al-1 complex (Table 4).
We also performed some Michael addition reactions of
diethyl malonates and thiophenol using LS-1 prepared
from lanthanum isopropoxide and observed nearly
equivalent enantiomeric excess to that of LS-1 prepared
from lanthanum chloride.
Figure 1. HPLC spectra of compound 4, using iso-
propanol:hexane (2:98) solvent mixture and 0.5 mL/min flow
rate.
3. Conclusion
Asymmetric catalytic Michael addition of thiophenols
and diethyl malonates with 2-methyl cyclopentenone,
where two stereogenic centers23 were created by simple
Michael addition reaction, gave an ee of 47% for the
thiophenol adduct and the diastereoselectivity was 45%.
Whereas on using diethylmalonate as Michael donor,
we obtained 60% de and 25% ee (Table 5, Fig. 1).
The lanthanum sodium aminodiol complex LS-1 is a
good chiral catalyst for Michael addition reactions of
dialkyl malonates and thiols giving high enantiomeric
excess. Our H NMR study indicates that the catalysts
are stable for 24 h and suggests prior coordination of
enone to the central metal atom. 2-Methyl cyclopen-
1

1056
N. Prabagaran, G. Sundararajan / Tetrahedron: Asymmetry 13 (2002) 1053–1058
4.3. Michael addition reaction of donors to
cycloalkenones
To 10 mol% of LS-1 complex, the cycloalkenone (1
equiv.) and the Michael donor (1 equiv.) were added
sequentially using THF solvent. After 30 min the reac-
tion mixture was quenched with 1N HCl, and the
product was extracted with ethyl acetate. The organic
4. Experimental
All reactions were performed under an inert atmo-
sphere of dry nitrogen. (R)-(+)-Styrene oxide, 2-
cyclopentenone, 2-cyclohexenone, LaCl3, La(OiPr)3,
thiophenols, and p-methyl thiophenols were purchased
from E. Merck and used as such. Anhydrous THF was
obtained by distillation over sodium-benzophenone
ketyl. All other reagents were purified by literature
procedures.
layer was washed successively with
a saturated
NaHCO3 solution, brine and dried over anhydrous
Na2SO4. Removal of the solvent under reduced pres-
sure gave a syrupy mass, which on flash chromatogra-
phy using acetone:hexane (4:96) as eluent gave the
products.
1H and 13C NMR spectra were recorded in CDCl3 with
4.3.1. 3-(p-Methyl-phenylthio)cyclopentanone, 2a. Yield:
90%; MS (EI, m/z): 206 (M+), 124, 91, 55; IR (CCl4,
1
JEOL 400 MHz (model GSX 400). H and 13C NMR
1
cm−1): 3024, 2944, 1747, 1149. H NMR (CDCl3, 400
data are reported in parts per million (l) downfield
from tetramethylsilane. The following abbreviations are
used for the observed resonance patterns: s=singlet,
d=doublet, t=triplet, q=quartet, m=multiplet, b=
broad. IR spectra were recorded with a Shimadzu
(model 470) IR spectrophotometer. Optical rotations
were measured with a JASCO DIP-370 digital polar-
imeter (with 50 and 10 mm cells). Mass spectra (high
and low resolution mass spectra) were obtained from
Finnigan MAT (model 8230) high resolution mass spec-
trometer. Waters HPLC with Waters 486 Tunable
absorbance detector (u) containing chiralcel OD
column for studying enantiomeric excess. ICP–AES
analysis was carried out by ARC 3410 ICP-AES with
mini torch.
MHz) l: 1.94–2.24 (m, 2H, C-4), 2.25–2.30 (m, 2H,
C-5), 2.34 (s, 3H), 2.46 (dd, 1H, 6.8 and 18.3 Hz, C-2),
2.55 (dd, 1H, 6.8 and 18.3 Hz, C-2) 3.77–3.89 (m, 1H,
C-3), 7.12 (d, 2H, 8.5 Hz), 7.3 (d, 2H, 8.5 Hz); 13C
NMR (CDCl3, 100 MHz) l: 21.08 (C-4), 29.26, 36.73
(C-5), 43.80 (C-2), 45.14 (C-3), 129.85, 130.26, 132.77,
137.71, 216.43; [h]D=3.5 (c=1.20, CCl4) ee=43% (lit:
[h]D=+1.8 (c=2.00, CCl4) ee=22.8%).
4.3.2. 3-(Phenylthio)cyclohexanone, 2b. Yield: 91%; MS
(EI, m/z): 206 (M+), 110, 97, 77, 55. IR (CCl4, cm−1):
1
3072, 2928, 1715 (CꢁO), 1433, 1302, 1213. H NMR
(CDCl3, 400 MHz) l: 1.67–1.78 (m, 2H, C-5), 2.10–2.15
(m, 2H, C-4), 2.28–2.66 (m, 4H, C-2, C-6), 3.39–3.45
(m, 1H, C-3), 7.25–7.32 (m, 3H), 7.4–7.43 (m, 2H). 13C
NMR (CDCl3, 100 MHz) l: 23.9 (C-5), 31.09 (C-4),
40.75 (C-6), 45.98 (C-2), 47.62 (C-3), 127.66, 128.95,
132.92, 133.08, 208.61. [h]D=38.45 (c=1.6, benzene)
ee=54% (lit: [h]D=16.4 (c=1.0, benzene) ee=22.5%).
4.1. Synthesis of LS-1
To a suspension of sodium hydride (41 mg, 1.71 mmol)
in THF was added amino diol 1 (290 mg, 0.836 mmol).
The mixture was allowed to stir for 1 h to obtain
sodiated amino diol.
4.3.3. 3-(p-Methylphenylthio)cyclohexanone, 2c. Yield:
90%. MS (EI, m/z) 220 (M+), 124, 97, 79, 55. IR (CCl4,
To LaCl3 (68 mg) the above sodiated amino diol (327
mg, 0.836 mmol) was added with sodium tert-butoxide
(0.4 mmol). The mixture was allowed to stir for 45 min
and the solution was filtered. Half of the filtrate could
be used ‘as is’ or alternatively the dried complex could
be used as catalyst for the Michael addition reactions.
1
cm−1): 2928, 1718, 1485, 1443, 1305, 1273. H NMR
(CDCl3, 400 MHz) l: 1.65–1.72 (m, 2H, C-5), 2.09–2.15
(m, 2H, C-4), 2.32 (s, 3H), 2.27–2.67 (m, 4H, C-2, C-6),
3.31–3.37 (m, 1H, C-3), 7.11 (d, 2H, 8.3 Hz), 7.32 (d,
2H, 8.3 Hz). 13C NMR (CDCl3, 100 MHz) l: 21.00
(C-5), 23.91 (C-4), 31.12, 40.72 (C-6), 46.33 (C-2), 47.65
(C-3), 129.70, 133.81, 137.98, 208.75. [h]D=+32.1 (c=
1.2, benzene) ee=45% (lit: [h]D=+70 (c=2.0, benzene)
ee=100%).
4.2. ICP analysis of the LS-1 complex
A suspension of LaCl3 (68 mg, 0.278 mmol) in dry
THF was treated with a solution of sodiated amino diol
(327 mg, 0.836 mmol) in dry THF and the mixture
stirred for 45 min at 0°C with sodium tert-butoxide (0.4
mmol). After separating and drying the supernatant
solution, a portion of the complex (26 mg) was taken
and made up to a volume of 10 mL using a 1:1 mixture
of water and conc. nitric acid. The aqueous solution
was filtered and this solution was used for ICP analysis.
The metal contents were found to be La: 286.57 mg/L
(calculated 290.58 mg/L) and Na: 140.21 mg/L (calcu-
lated 144.28 mg/L).
4.3.4. 3-(Phenylthio)cyclopentanone, 2d. Yield: 95%; MS
(EI, m/z): 192 (M+) 110, 83, 55; IR (CCl4, cm−1): 3024,
2945, 1748 (CꢁO), 1150; H NMR (CDCl3, 400 MHz)
l: 1.96–2.23 (m, 2H, C-4), 2.26–2.37 (m, 2H, C-5) 2.45
(dd, 1H, 6.8 and 18.0 Hz, C-2), 2.59 (dd, 1H, 6.8 and
18.5 Hz, C-2), 3.85–3.92 (m, 1H, C-3), 7.24–7.41 (m,
5H); 13C NMR (CDCl3, 100 MHz) l: 29.18 (C-4), 36.62
(C-5), 43.22 (C-2), 45.09 (C-3), 127.27, 128.98, 131.81,
134.08, 216.6; [h]D=+3.2 (c=1.0, CCl4) ee=39% (lit:
[h]D=1.8 (c=1.54, CCl4) for ee=22.5%).
1

N. Prabagaran, G. Sundararajan / Tetrahedron: Asymmetry 13 (2002) 1053–1058
1057
4.3.5. 3-[Bis(ethoxycarbonyl)methyl]cyclopentanone, 3a.
Yield: 82%; MS (EI, m/z): 242 (M+), 197, 160, 83. IR
4.3.10.
3-[Bis(tert-butoxycarbonyl)methyl]cyclohexa-
none, 3f. Yield: 80%; MS (EI, m/z): 312 (M+), 256, 200,
(CCl4, cm−1): 2976, 2928, 1744, 1734, 1148; H NMR
96, 57. IR (CCl4, cm−1): 2976, 2928, 1740, 1724, 1366,
1
1
(CDCl3, 400 MHz) l: 1.20 (t, 3H, 7.3 Hz), 1.21 (t, 3H,
7.32 Hz), 1.58–1.66 (m, 1H, C-4), 1.93–2.0 (m, 1H,
C-4), 2.1–2.31 (m, 1H, C-3), 2.45–2.86 (m, 4H, C-2,
C-5), 3.27 (d, 1H, 9.28 Hz, C-6), 4.12–4.19 (m, 4H); 13C
NMR (CDCl3, 100 MHz) l: 13.93, 27.34 (C-4), 36.18
(C-3), 38.06 (C-5), 42.77 (C-2), 56.38 (C-6), 61.47,
61.57, 167.95, 168.04, 217.11; [h]D=+27.1 (c=1.05,
CHCl3) ee=28% (lit: [h]D=+28.35 (c=1.89, CHCl3)
ee=82%).
1158; H NMR (CDCl3, 400 MHz) l: 1.39 (s, 9H), 1.40
(s, 9H), 1.41–1.65 (m, 2H, C-5), 1.89–2.02 (m, 2H, C-4),
2.14–2.21 (m, 1H, C-3), 2.30–2.40 (m, 4H, C-2, C-6),
3.01 (d, 1H, 7.81 Hz, C-7); 13C NMR (CDCl3, 100
MHz) l: 27.56, 27.94 (C-5), 28.79 (C-4), 37.88 (C-3),
41.1 (C-6), 45.2 (C-2), 58.75 (C-7), 81.85, 81.83, 167.18,
167.28, 210.09; [h]D=+6.5 (c=2.0, CHCl3) ee=96%
(lit: [h]D=4.2 (c=1.02, CHCl3) ee=65%.
4.3.11. 3-(Phenylthio)-2-methylcyclopentanone, 4. Yield:
90%; MS (EI, m/z): 206 (M+); IR (CCl4, cm−1): 1744;
1H NMR (CDCl3, 400 MHz) l: 1.11 (d, 3H, 6.9 Hz,
C-6), 1.77–1.80 (m, 2H, C-4), 2.08–2.18 (m, 3H, C-2,
C-5), 2.25–2.37 (m, 1H, C-3), 7.27–8.1 (m, 5H); 13C
NMR (CDCl3, 100 MHz) l: 10.2 (C-6), 28.43 (C-4),
36.77 (C-5), 44.29 (C-2), 45.53 (C-3), 128.43, 129.58,
130.03, 133.59, 219.82.
4.3.6. 3-[Bis(ethoxycarbonyl)methyl]cyclohexanone, 3b.
Yield: 85%; MS (EI, m/z): 256 (M+), 211, 182, 160, 97;
IR (CCl4, cm−1): 2968, 2930, 1754, 1724, 1443, 1359,
1
1134; H NMR (CDCl3, 400 MHz) l: 1.27 (t, 3H, 7.33
Hz), 1.28 (t, 3H, 7.27 Hz), 1.52–1.69 (m, 2H, C-5),
1.96–2.11 (m, 2H, C-4), 2.22–2.31 (m, 1H, C-3), 2.38–
2.47 (m, 2H, C-6), 2.49–2.57 (m, 2H, C-2), 3.35 (d, 1H,
7.82 Hz, C-7), 4.20 (q, 2H, 7.32 Hz), 4.21 (q, 2H, 7.32
Hz); 13C NMR (CDCl3, 100 MHz) l: 14.07, 14.10,
27.50 (C-5), 29.35 (C-4), 36.32 (C-3), 38.20 (C-6), 42.91
(C-2), 56.52 (C-7), 61.62, 61.45, 168.09, 168.18, 217.27;
[h]D=+2.9 (c=2.13, CHCl3) ee=84% (lit: [h]D=+2.9
(c=2.56, CHCl3) ee 81%).
4.3.12. 3-[Bis(ethoxycarbonyl)methyl]-2-methylcyclopen-
tanone, 5. Yield: 86%; MS (EI, m/z): 256 (M+). IR
1
(CCl4, cm−1): 1731, 1651; H NMR (CDCl3, 400 MHz)
l: 1.1 (d, 3H, 6.9 Hz, C-6), 1.27 (m, 6H), 1.68–1.76 (m,
2H, C-4), 2.03–2.20 (m, 1H, C-3), 2.33–2.54 (m, 2H,
C-5), 2.95 (m, 1H, C-2), 3.27 (d, 1H, 6.8 Hz, C-7), 4.20
(q, 4H, 3.5 Hz); 13C NMR (CDCl3, 100 MHz) l: 13.19,
14.05 (C-6), 24.68 (C-4), 36.73 (C-3), 43.62 (C-5), 47.83
(C-2), 54.7 (C-7), 61.50, 61.55, 167.95, 168.37, 216.82.
4.3.7. 3-[Bis(benzyloxycarbonyl)methyl]cyclopentanone,
3c. Yield: 84%; MS (EI, m/z): 366 (M+), 289, 107, 91;
1
IR (CCl4, cm−1): 2978, 2928, 1747, 1733, 1452, 1398; H
NMR (CDCl3, 400 MHz) l: 1.58–1.77 (m, 2H, C-4),
1.97–2.98 (m, 5H, C-2, C-3, C-5), 3.33 (d, 1H, 7.81 Hz,
C-6), 5.11 (s, 2H), 5.12 (s, 2H), 7.20–7.41 (m, 10H). 13C
NMR (CDCl3, 100 MHz) l: 24.41 (C-4), 38.32 (C-3),
40.53 (C-5), 41.06 (C-2), 55.72 (C-6), 66.28, 66.30,
128.13, 128.24, 128.53, 135.13, 135.24, 170.83, 170.92,
217.30. [h]D=+31.9 (c=1.27, CHCl3) ee=93% (lit:
[h]D=+28.35 (c=1.89, CHCl3) ee=85%).
Acknowledgements
A research fellowship to one of the authors by the
Council of Scientific and Industrial Research, India is
gratefully acknowledged. We thank CSIR-India (No.
01/1476/97/EMR-II) for financial support and RSIC
(IIT-Madras) for 400 MHz NMR spectra.
4.3.8. 3-[Bis(benzyloxycarbonyl)methyl]cyclohexanone,
3d. Yield: 86%; MS (EI, m/z): 380 (M+), 289, 91. IR
(CCl4, cm−1): 3040, 2944, 1753, 1721; 1H NMR (CDCl3,
400 MHz) l: 1.40–1.60 (m, 2H, C-5), 1.81–1.96 (m, 2H,
C-4), 2.11–2.19 (m, 1H, C-3), 2.27–2.38 (m, 2H, C-6),
2.43–2.51 (m, 2H, C-2), 3.33 (d, 1H, 7.81 Hz, C-7), 5.06
(s, 2H), 5.07 (s, 2H), 7.17–7.25 (m, 10H); 13C NMR
(CDCl3, 100 MHz) l: 24.46 (C-5), 28.59 (C-4), 38.06
(C-3), 40.90 (C-6), 45.00 (C-2), 56.63 (C-7), 66.76,
67.21, 128.30, 128.47, 128.51, 135.07, 135.17, 167.48,
167.58, 209.34; [h]D=+1.2 (c=1.68, CHCl3) ee=95%
(lit: [h]D=+1.1 (c=2.21, CHCl3) ee=88%.
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(KBr, cm−1): 2976, 1741, 1718, 1401, 1129; H NMR
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