Nanocrystalline MgO for asymmetric Henry and Michael reactions

Article abstract of DOI:10.1021/ja0440248

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 center. We

Full text of DOI:10.1021/ja0440248

Published on Web 09/01/2005
Nanocrystalline MgO for Asymmetric Henry and Michael
Reactions
Boyapati M. Choudary,*,† Kalluri V. S. Ranganath,‡ Ujjwal Pal,‡
Mannepalli L. Kantam,*,‡ and Bojja Sreedhar‡
Contribution from Ogene Systems (I) PriVate Limited, Hyderabad, India, and
Inorganic and Physical Chemistry DiVision, Indian Institute of Chemical Technology,
Hyderabad-500 007, India
Received October 1, 2004; E-mail: mlakshmi@iict.res.in; bmchoudary@yahoo.com
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 center. We herein report the design and development of a truly
recyclable heterogeneous catalyst, nanocrystalline magnesium oxide, for the asymmetric Henry reaction
(AH) to afford chiral nitro alcohols with excellent yields and good to excellent enantioselectivities (ee’s) for
the first time. Bronsted hydroxyls are the sole contributors for the ee, while they add on to the activity in
AH. It is demonstrated that the hydrogen bond interactions between the -OH groups of (S)-(-)-binol and
the -OH groups of MgO are essential for the induction of enantioselectivity. Further, to prove the above
hypothesis, we have successfully carried out another reaction, asymmetric Michael reaction (AM) with
nanocrystalline MgO. The reusable and suitably aligned nanocrystalline MgO-catalyzed AH and AM reactions
afforded chiral products with comparable ee’s to that of the homogeneous system.
Introduction
reactions with good to excellent ee’s are accomplished using
alkaloids,8,9 chiral crown ethers in the presence of bases,10
The carbon-carbon bond forming reactions are ubiquitous
in synthetic organic chemistry, which generated increasing
interest from both industrial and academic researchers over the
last few decades to find ways for economical processes.1,2
Nitroaldol and Michael reactions are the fundamental synthetic
tools for the construction of C-C bonds.3 The nitro group of
these products can undergo the Nef reaction,4 reduction to amino
group, or nucleophilic displacement.5 The asymmetric Henry
(AH) reactions with impressive enantioselectivities (ee’s) are
realized using a dinuclear zinc-chiral semi-azacrown6 complex
or copper bisoxazoline complexes.7 Asymmetric Michael (AM)
proline and proline-derived catalysts,11 diamines,12 natural
proteins,13 amino alcohols,14 and binol-derived complexes15 in
homogeneous media. In the area of heterogenized catalysts,
chiral polymers provide moderate ee’s in the AM reactions.16
(7) (a) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. T.;
Downey, C. W. J. Am. Chem. Soc. 2003, 125, 12692. (b) Christensen, C.;
Juhl, K.; Hazell, R. G.; Jorgensen, K. A. J. Org. Chem. 2002, 67, 4875.
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Yamashita, H.; Mukaiyama, T. Chem. Lett. 1985, 363.
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Chem. 1986, 51, 4710. (b) Kim, D. Y.; Huh, S. C.; Kim, S. M. Tetrahedron
Lett. 2001, 42, 6299. (c) Kacprzak, K.; Gawronski, J. Synthesis 2001, 961.
(d) Tian, S.-K.; Chen, Y.; Hang, J.; Tang, L.; Deng, L. Acc. Chem. Res.
2004, 37, 621. (e) Vakulya, B.; Varga, S.; Csampai, A.; Soos, T. Org.
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S.; Pham, V. Org. Lett. 2000, 2, 2975. (c) List, B.; Pojarliev, P.; Martin,
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V. Org. Biomol. Chem. 2005, 1.
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† Ogene Systems (I) Private Limited.
‡ Indian Institute of Chemical Technology.
(1) (a) Li, G. Y.; Zheng, G.; Noonan, A. F. J. Org. Chem. 2001, 66, 8677. (b)
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B. M. Science 1991, 254, 1471. (d) Trost, B. M. Angew. Chem., Int. Ed.
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9
10.1021/ja0440248 CCC: $30.25 © 2005 American Chemical Society
J. AM. CHEM. SOC. 2005, 127, 13167-13171
13167

A R T I C L E S
Choudary et al.
Table 1. Achiral Henry Reaction Catalyzed by Different
Scheme 1. Asymmetric Henry and Michael Reactions Catalyzed
by Nanocrystalline Magnesium Oxide
Crystallites of MgO between Benzaldehyde and Nitromethane at
25 °Ca
entry
catalyst
time (h)
yield (%)b
1
2
3
4
5
NAP-MgO
NA-MgO
CM-MgO
Sil-NAP-MgO
Sil-NA-MgO
6
10
18
20
30
95
95
20c
90
90
a Conditions: benzaldehyde (1.0 mmol, 0.1 mL), nitromethane (5.0 mmol,
0.305 g), NAP-MgO (0.125 g), dry THF (5 mL). b Isolated yields. c The
byproduct was dehydrated Henry product (olefin).
A breakthrough both in AM and AH catalytic reactions is
achieved with the introduction of in situ prepared heterobime-
tallic catalysts, composed of both Lewis acidic sites and Lewis/
Bronsted basic sites.17 Transition metal chiral complexes, single-
site catalysts with a defined shape and stereochemistry, induces,
in general, higher enantioselectivity in asymmetric synthesis
since they permit unidirectional introduction of the reacting
species onto a prochiral substrate in the three-dimensional space
to generate the asymmetric center. Conversely, heterogeneous
catalysts 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 center is a challenging problem. Nanocrystalline
metal oxides find excellent applications as active adsorbents
for gases and destruction of hazardous chemicals and catalysts
for various organic transformations.18,19 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 center.19d Recently, we evolved
the single-site nanocrystalline MgO for the synthesis of chiral
epoxy ketones.19d
Table 2. Asymmetric Henry Reaction between Nitromethane and
Benzaldehyde Catalyzed by NAP-MgO with Different Ligands at
-78 °C
entry
ligand
yield (%)a
ee (%)b
1
(S)-(-)-binol
95, 70,c 50,d
40,e 95,f 0,f 0g
95
90, 58,c 10,d
0,e 90f
2
3
4
5
6
7
protected -OHs of (S)-(-)-binol
0
(S)-(-)-1,1′-binaphthyl-2,2′-diamine 90
30
40
30
0
(1R,2R)-(-)-1,2-diaminocyclohexane 90
(DHQD)2PHAL
L-proline
(+)-diethyl L-tartrate
80
NR
90
20
a Isolated yields. b Absolute configurations were determined to be S.
c With NA-MgO. d With CM-MgO. e With silylated NAP-MgO. f Fifth
cycle. g Without catalyst; ee’s were measured by Diacel Chiralcel HPLC
using OD column with 3% 2-propanol in hexane. Conditions: benzaldehyde
(1.0 mmol), nitromethane (5.0 mmol), NAP-MgO (0.125 g), dry THF (5
mL), (S)-(-)-binol (0.040 g).
Table 3. Asymmetric Henry Reaction between Benzaldehyde and
Nitromethane Catalyzed by NAP-MgO with Different Solvents at
25 °Ca
entry
solvent
time (h)
yield (%)b
ee (%)c
1
2
3
4
5
methanol
24
24
24
15
06
40
30
0
40
30
0
55
60
acetonitrile
1,2-dichloroethane
toluene
95d
95d
We herein report the design and development of a truly
recyclable heterogeneous catalyst, nanocrystalline magnesium
oxide, for the AH and AM reactions to afford chiral nitro
alcohols and Michael adducts in good to excellent yields and
enantioselectivities for the first time (Scheme 1).
THF
a Conditions: benzaldehyde (1.0 mmol, 0.1 mL), nitromethane (5.0 mmol,
0.305 g), NAP-MgO (0.125 g), solvent (5 mL). b Isolated yields. The
byproduct was dehydrated Henry product (olefin) in case of entries 1 and
2. c Absolute configurations were determined to be S. d No byproduct
Results and Discussion
Various magnesium oxide crystals20 [commercial MgO,
CM-MgO (SSA: 30 m2/g), conventionally prepared MgO,
NA-MgO (SSA: 250 m2/g), and aerogel-prepared MgO, NAP-
MgO (SSA: 590 m2/g)] were initially screened in the achiral
Henry reaction between benzaldehyde and nitromethane at room
temperature. NAP-MgO and NA-MgO gave nitro alcohols with
good yields, while CM-MgO afforded olefin product (major)
along with nitroaldol product (Table 1).
Encouraged with the initial success in the achiral Henry
reaction, we carried out AH reaction of benzaldehyde with
nitromethane. In the process of optimization of the AH reaction,
we explored different samples of MgO (Table 2, entry 1) with
various chiral auxiliaries (Table 2) and solvents (Table 3) at
different temperatures (Table 4). Among the MgO samples
screened in the AH reaction, the NAP-MgO was found to be
superior than the NA-MgO and CM-MgO in terms of yields
and ee’s. The ee’s of the AH product are 90, 58, and 10% using
the NAP-MgO, NA-MgO, and assorted crystals of CM-MgO,
respectively (Table 2). (S)-(-)-1,1′-Bi-2-naphthol [(S)-(-)-
binol], a versatile chiral auxiliary in various asymmetric or-
ganic transformations,21 offered optimum ee in the AH reaction
of benzaldehyde with nitromethane. As the temperature de-
creases, ee increases remarkably with decrease of rate of
(17) (a) Arai, T.; Sasai, H.; Aoe, K.; Okamura, K.; Date, T.; Shibasaki, M.
Angew. Chem., Int. Ed. Engl. 1996, 35, 104. (b) Arai, T.; Yamada, Y. M.
A.; Yamamoto, N.; Sasai, H.; Shibasaki, M. Chem.sEur. J. 1996, 2, 1368.
(c) Kim, Y. S.; Matsunaga, S.; Das, J.; Sekine, A.; Ohshima, T.; Shibasaki,
M. J. Am. Chem. Soc. 2000, 122, 6506. (d) Matsunaga, S.; Ohshima, T.;
Shibasaki, M. Tetrahedron Lett. 2000, 41, 8473. (e) Sasai, H.; Suzuki, T.;
Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992, 114, 4418. (f)
Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.; Shibasaki, M.
J. Org. Chem. 1995, 60, 7388.
(18) (a) Lucas, E.; Decker, S.; Khaleel, A.; Seitz, A.; Fultz, S.; Ponce, A.; Li,
W.; Carnes, C.; Klabunde, K. J. Chem.sEur. J. 2001, 7, 2505. (b) Schlogl,
R.; Abd Hamid, S. B. Angew. Chem., Int. Ed. 2004, 43, 1628. (c) Bell, A.
T. Science 2003, 299, 1688. (d) Choudary, B. M.; Ranganath, K. V. S.;
Yadav, J.; Kantam, M. L. Tetrahedron Lett. 2005, 46, 1369.
(19) (a) Carnes, C. L.; Klabunde, K. J. Langmuir 2000, 16, 3764. (b) Sharghi,
H.; Sarvari, M. H. Synthesis 2002, 8, 1057 (c) Banerjee, M.; Roy, S. Chem.
Commun. 2003, 534. (d) Choudary, B. M.; Kantam, M. L.; Ranganath, K.
V. S.; Mahender, K.; Sreedhar, B. J. Am. Chem. Soc. 2004, 126, 3396. (e)
Sarvari, M. H.; Sharghi, H. J. Org. Chem. 2004, 69, 6953. (f) Kim, Y. J.;
Varma, R. S. Tetrahedron Lett. 2004, 45, 7205.
(20) Utamapanya, S.; Klabunde, K. J.; Schlup, J. R. Chem. Mater. 1991, 3,
175.
(21) Brunel, J. M. Chem. ReV. 2005, 105, 857.
9
13168 J. AM. CHEM. SOC. VOL. 127, NO. 38, 2005

Nanocrystalline MgO for AH and AM Reactions
A R T I C L E S
Table 4. Asymmetric Henry Reaction between Benzaldehyde and
Scheme 2. Asymmetric Henry Reaction of R-Keto Esters with
Nitromethane Catalyzed by NAP-MgO at -78 °C
Nitromethane Catalyzed by NAP-MgO at Different Temperaturesa
entry
T (°
C)
time (h)
yield (%)b
ee (%)
1
2
3
4
40
25
0
4
6
7
70c
90
95
95
30
60
70
90
-78
12
a Conditions: benzaldehyde (1.0 mmol, 0.1 mL), nitromethane (5.0 mmol,
0.305 g), NAP-MgO (0.125 g), THF (5 mL), (S)-binol (5.0 mmol, 0.040
g). b Isolated yields. Conversions are 100% at all temperatures. c The
byproduct was dehydrated Henry product (olefin); ee’s were measured by
Diacel Chiralcel HPLC using OD column with 3% 2-propanol in hexane.
Table 6. Asymmetric Henry Reaction between R-Keto Esters and
Nitromethane Catalyzed by NAP-MgO at -78 °C
entry
substrate
time (h)
product
yield (%)a
ee (%)d
Table 5. Asymmetric Henry Reaction Catalyzed by NAP-MgO
with Substituted Benzaldehydes and Nitromethane at -78 °Ca
1
2
4a
4b
20
24
5a
5b
75, 40,b 30c
70
98, 0,c 0d
98
a Isolated yields. b With NA-MgO. c With CM-MgO. d Absolute con-
figurations were determined to be S.
Table 7. Effect of Ligand on AM Reaction between Chalcone and
Nitromethane Catalyzed by NAP-MgO at 25 °Ca
entry
ligand
time (h) yield (%)b ee (%)
1
2
3
4
5
6
7
8
9
(1R,2R)-(-)-1,2-diaminocyclohexane
(1R,2R)-(+)-1,2-diphenylethylenediamine
(1S,2R)-(+)-2-amino-1,2-diphenylethanol
(1R,2S)-(-)-N-methylephedrine
(+)-diethyl L-tartrate
8
8
95
95
90
90
50
90
NR
NR
90
90
82
60
0
0
60
0
12
12
18
12
15
15
12
(S)-(-)-1,1′-binaphthyl-2,2′-diamine
(S)-(-)-binol
entry
substrate
time (h)
product
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
12
18
15
16
15
20
20
15
15
18
18
15
3a
3b
3c
3d
3e
3f
3g
3h
3i
95
95
95
90
90
80
95
90
90
80
70
70
90
98
80
98
77
85
70
70
60
86
70
60
L-proline
L-proline methyl ester
0
80
a In all cases 25 mol % of ligand was used. Conditions: chalcone (1.0
mmol, 0.208 g), nitromethane (50.0 mmol, 3.05 g), NAP-MgO (0.125 g),
dry THF (5 mL). b Isolated yields.
between chalcone and nitromethane, was studied using nano-
materials. When we tried the asymmetric Michael (AM) reaction
with the (S)-(-)-binol, no reaction took place due to inadequate
basicity.10,17d To enhance the basicity, we have evaluated several
chiral amine ligands in the asymmetric Michael reaction (Table
7). Among the MgO samples screened in the AM reaction of
chalcone with nitromethane using (1R,2R)-(-)-diaminocyclo-
hexane (DAC) as chiral auxiliary, the NAP-MgO was found to
be superior to NA-MgO and CM-MgO in terms of yields and
ee’s. The ee’s of the product are 90, 46, and 5% using the NAP-
MgO, NA-MgO, and assorted crystals of CM-MgO, respec-
tively. In an attempt to optimize the AM reaction, the effect of
solvent and temperatures was studied. NAP-MgO, using DAC
as chiral auxiliary in THF at -20 °C, was found to be the best
system.
In general, chiral bidentate systems composed of primary
and secondary amines afforded better ee’s (Table 7, entries
1-3, 6, and 9), while chelation with tertiary amine, -COOH,
or -OH displayed no ee’s (Table 7, entries 4, 5, 7, and 8).
In the AM reaction with NAP-MgO, the rate of the reaction
is faster in the presence of chiral auxiliary. As the lig-
and concentration increases, the rate of the reaction increases
with the increase of ee (Figure 1). These results are in
consonance with the earlier reported ligand acceleration effects23
that include metal-diamine accelerated asymmetric Michael
reactions.24
10
11
12
1j
1k
1l
3j
3k
3l
a Conditions: benzaldehyde (1.0 mmol), nitromethane (5.0 mmol), NAP-
MgO (0.125 g), dry THF (5 mL), (S)-(-)-binol (0.040 g). b Isolated yields.
c Absolute configurations were determined to be S.
reaction. The solvent THF and temperature of -78 °C showed
optimum ee’s.
To widen the scope, NAP-MgO was tested in the AH reaction
of aromatic, aliphatic, and cyclic aldehydes with nitromethane.
When benzaldehydes are substituted at the 4-position with
electron-withdrawing (EW) groups, higher ee’s are observed
than the one bearing electron-donating (ED) groups at the
4-position (Table 5, entries 2, 4, 6, and 8). On the other hand,
in the AH reaction using NAP-MgO, 2-substituted benzalde-
hydes with either EW or ED groups exhibit a decrease of ee
when compared with the corresponding 4-substituted benzal-
dehydes, which may be ascribed to the steric hindrance for the
unidirectional entry of reacting species (Table 5, entries 2-9).
NAP-MgO catalyzed the AH reaction of R-keto esters with
nitromethane to â-nitro R-hydroxy esters, which are vital chiral
intermediates with quaternary carbon centers in higher ee’s than
reported22 using (S)-binol as a chiral auxiliary (Scheme 2).
Even though the three forms of magnesium oxide crystals
catalyze this reaction, only NAP-MgO induces the enantiose-
lectivity (Table 6).
(22) (a) Christensen, C.; Juhl, K.; Hazell, R. G.; Jorgensen, K. A. Chem.
Commun. 2001, 2222. (b) Du, D.-M.; Lu, S.-F.; Fang, T.; Xu, J. J. Org.
Chem. 2005, 70, 3712.
Spurred with the success of AH reactions, another important
C-C bond formation, asymmetric Michael (AM) reaction
9
J. AM. CHEM. SOC. VOL. 127, NO. 38, 2005 13169

A R T I C L E S
Choudary et al.
induction was found with the EW and ED substituents compared
to Ar2 (Table 8).
To understand the relation between structure and reactivity
in both AH and AM reactions, it is better to know the structure
and nature of the reactive sites of NAP-MgO. NAP-MgO has
three-dimensional polyhedral structure, which having the pres-
ence of high surface concentrations of edge/corner and various
exposed crystal planes (such as 002, 001, and 111) leads to
inherently high surface reactivity per unit 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 Mg2+, Lewis basic sites O2- and O-, lattice
bound and isolated Bronsted hydroxyls, and anionic and cationic
vacancies.25 Both Henry and Michael reactions are known to
be driven by base catalysts,26 and accordingly, the surface -OH
and O2- of these oxide crystals are expected to trigger these
reactions. To examine the role of -OH, the Sil-NA-MgO and
Sil-NAP-MgO,27 devoid of free -OH, were tested in AH and
AM reactions. It is found that the silylated MgO samples had
reaction times longer than that of the corresponding MgO
samples in both reactions, and no ee is observed (Tables 2 and
8, entry 1). These results indicate that Bronsted hydroxyls are
the sole contributors for the ee, while they add on to the activity
in AH and AM reactions, which is largely driven by Lewis basic
O2- and O-sites. When protected hydroxyls of (S)-(-)-binol
(Table 2) were used in place of (S)-(-)-binol in the AH reaction
catalyzed by NAP-MgO, no ee was observed. Similarly, in the
AM reaction, a bidentate system composed of at least one
primary or secondary amine gave better ee’s and tertiary amine
gave no ee. These results establish that the hydrogen bond
interactions between the -OH or -NH groups of chiral auxiliary
and -OH groups of MgO are essential for the induction of
enantioselectivity. Although both the NAP-MgO and NA-MgO
possess defined shapes and the same average concentrations of
surface -OH groups, a possible rationale for the display of
higher ee by the NAP-MgO is that the -OH groups present on
edge and corner sites on the NAP-MgO, which are stretched in
three-dimensional space, are more isolated and accessible for
the chiral ligand for greater alignment, whereas the hindered
-OHs situated on flat planes in closer proximity with each other
present in relatively large numbers on NA-MgO28 disable proper
alignment for the chiral ligand.
Figure 1. Effect of ligand concentration on the rate of the reaction as a
function of time at -20 °C.
Table 8. Asymmetric Michael Reaction between Nitroalkanes and
Various Michael Acceptors Catalyzed by NAP-MgO at -20 °C
Using (1R,2R)-(-)-1,2-Diaminocyclohexane
Michael
Michael
donor
entry
acceptor
time (h)
product
yield (%)a
ee (%)b
1
6a
2
12
7a
95, 70,c 30,d 96, 48,c 5,d
95,f 0g 0,e 96f
2
3
4
5
6
7
8
9
10
6b
6c
6a
6d
6e
6f
6g
6h
6i
2
2
15
18
16
24
24
20
30
72
72
7b
7c
7d
7e
7f
7g
7h
7i
90
70
95
90
84
90
74
95
70
82
68
66
80
63
0
2a
2a
2a
2a
2a
2a
2a
NR
NR
7j
0
a Isolated yields. b Absolute configurations were found to be R. c With
NA-MgO. d With CM-MgO. e With silylated NAP-MgO. f Fifth cycle.
g Without catalyst. Absolute configurations were determined to be R.
The XPS spectrum of the CH3-NO2 treated NAP-MgO for
the Mg 2p exhibits two lines at 48.70 and 49.65 eV, which can
be attributed to magnesium in NAP-MgO and Mg-C of O2N-
H2C-MgO (8),29 respectively (Figure 1, Supporting Informa-
tion). An endotherm at 450 °C that gives off a fragment (m/z )
60 amu), corresponding to NO2CH2+• in DTA-TGA-MS of the
nitromethane-treated NAP-MgO (Figure 2, Supporting Informa-
tion), further reiterates the formation of surface 8 moiety. When
the nitromethane-treated NA-MgO was subjected to DTA-TGA-
MS, no such endotherm is visible corresponding to 8. This is
To widen the scope, a system composed of NAP-MgO-DAC
in THF was evaluated in the AM reaction of different acyclic
enones with nitromethane and 2-nitropropane. Chalcones pro-
vided good to excellent yields and ee’s (Table 8, entries 1-7).
Conversely, no AM reaction was observed using aliphatic
enones.
It can be seen that the unsubstituted phenyls of chalcone gave
the best ee. Substitution on either of the phenyls of the chalcones
and the nature of substituents have a considerable impact on
the stereochemistry of the products. With respect to the effect
of substituents on the Ar2 group, EW substituents gave higher
enantioselectivity than did the ED substituents. Evaluating the
effect of substituents in the Ar1 group, the lowest asymmetric
(25) (a) Jeevanandam, P.; Klabunde, K. J. Langmuir 2002, 18, 5309. (b)
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9
13170 J. AM. CHEM. SOC. VOL. 127, NO. 38, 2005

Nanocrystalline MgO for AH and AM Reactions
A R T I C L E S
Scheme 3. Proposed Mechanism for Asymmetric Henry and Michael Reactions Catalyzed by NAP-MgO
due to the presence of low concentrations of Mg+ ion (0.5%)
in NA-MgO. In AH and AM reactions, O2-/O- of NAP-MgO
abstracts an acidic proton of the nitromethane, giving a
carbanion, which forms a complex with the unsaturated Mg+
site (Lewis acid-type) of NAP-MgO. The AH and AM reactions
proceed via dual activation of both substrates (nucleophiles and
electrophiles) by NAP-MgO. Thus, the Lewis base (O2-/O-)
of the catalyst activates nitroalkanes, and the Lewis acid moiety
(Mg2+/Mg+) activates the carbonyls of aldehydes and enones
(Scheme 3).30
The activation of carbonyl through the Lewis acid site is
indeed observed earlier in achiral Henry reaction.31a,b The
activation of carbonyls through hydrogen bonding by Lewis
acids is also known.31c Similarly, acid-base dichotomy is well-
known in biological systems.32 The chiral auxiliaries, binol, or
DAC bound to NAP-MgO with proper alignment via hydrogen
bonds direct the delivery of -CH2NO2 stereoselectively to the
Mg+ (Lewis acid)-activated carbonyl of aldehydes or chalcones
via oxygen coordination to afford the chiral nitro alcohols or
Michael adducts. The NAP-MgO was reused after heating the
catalyst at 250 °C for 1 h under nitrogen atmosphere. Thus, the
catalyst was reused five times, which showed consistent yields
and ee’s both in AH and AM reactions (Table 2, entry 1 and
Table 8, entry 1). The reusable and suitably aligned nanocrys-
talline MgO with reactants catalyzed AH and AM reactions
affords chiral nitro alcohols and Michael adducts with compa-
rable ee’s to that of the homogeneous systems.
Acknowledgment. K.V.S.R. and U.P. thank the CSIR India
for the award of fellowship. Nanocrystalline MgO catalysts were
obtained from NanoScale Materials Inc., Manhattan, Kansas,
USA.
Note Added after ASAP Publication. In the version
published on the Internet September 1, 2005, there was an error
in Scheme 3. It is correct in the version published September
9, 2005, and in the print version.
Supporting Information Available: Experimental section and
product characterization. This material is available free of charge
via the Internet at http://pubs.acs.org.
(30) (a) Shibasaki, M.; Kanai, M. Chem. Pharm. Bull. 2001, 49, 511. (b) Sasai,
H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc.
1995, 117, 6194. (c) Shibasaki, M.; Kanai, M.; Funabashi, K. Chem.
Commun. 2002, 1989.
(31) (a) Kisanga, P. B.; Verkade, J. G. J. Org. Chem. 1999, 64, 4298. (b)
McNulty, J.; Dyck, J.; Larichev, J.; Capretta, A.; Robertson, A. J. Lett.
Org. Chem. 2004, 1, 137. (c) Pikho, P. M. Angew. Chem., Int. Ed. 2004,
43, 2062.
JA0440248
(32) (a) Barrett, A. G. M.; Graboski, G. G. Chem. ReV. 1986, 86, 751. (b) Barrett,
A. G. M. Chem. Soc. ReV. 1991, 20, 95.
9
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