The one-pot Wittig reaction: A facile synthesis of α,β- unsaturated esters and nitriles by using nanocrystalline magnesium oxide

Article abstract of DOI:10.1002/adsc.200606001

Nanocrystalline magnesium oxide was found to be an effective heterogeneous, solid base catalyst for the one-pot Wittig reaction to afford α,β-unsaturated esters and nitriles in excellent yields with high E-stereoselectivity in the presence of triphenylphosphine under mild conditions.

Full text of DOI:10.1002/adsc.200606001

FULL PAPERS
DOI: 10.1002/adsc.200606001
The One-Pot Wittig Reaction: A Facile Synthesis of a,b-Unsatu-
rated Esters and Nitriles by Using Nanocrystalline Magnesium
Oxide
Boyapati M. Choudary,a,* Koosam Mahendar ,b M. Lakshmi Kantam,b,*
Kalluri V. S. Ranganath,b and Taimur Atharb
a
Ogene Systems (I) Pvt. Ltd, # 11-6-56, GSR Estates, Moosapet, Hyderabad, 500037, India
Fax: (+91)-40-2377-5566; e-mail: bmchoudary@yahoo.com
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
b
Fax: (+91)-40-27160921or; e-mail: lkmannepalli@yahoo.com
Received: January 2, 2006; Revised: June 23, 2006; Accepted: July 11, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Nanocrystalline magnesium oxide was Keywords: a-fluoro-a,b-unsaturated esters; nano-
found to be an effective heterogeneous, solid base crystalline magnesium oxide; triphenylphosphine;
catalyst for the one-pot Wittig reaction to afford a,b- a,b-unsaturated esters; Wittig reaction
unsaturated esters and nitriles in excellent yields
with high E-stereoselectivity in the presence of tri-
phenylphosphine under mild conditions.
Introduction
ligands. Lebel et al. reported the methylenation of al-
dehydes by rhodium complexes in the presence of
The development of methods for the stereoselective PPh3 using CH2N2 or TMSCHN2 as the diazo precur-
formation of C=C double bonds represents one of the sors.[9] The Wadsworth–Emmons (WWE) reaction is
most important challenges in organic synthesis.[1] The also a widely used method for the preparation of a,b-
Wittig reaction and its variants have been acknowl- unsaturated esters as a well established alternative to
edged as powerful and versatile tools in organic syn- the Wittig olefination. The phosphonate anions are
thesis for the formation of C=C double bonds.[2] The strongly nucleophilic and react readily with aldehydes
most important intermediates for several biologically to form olefins. Generally, the WWE is performed in
active molecules[3] ánd fluoro compounds[4] have been the presence of relatively strong bases such as n-bu-
synthesized through the Wittig reaction.
tyllithium, potassium tert-butoxide, sodium hydride,
The most impressive variant in the Wittig reaction LDA, DBU, Triton B, N-ethylpiperidine etc. under
is the replacement of the three step-process, involving homogenous conditions.[2b,10]
the preparation of a phosphonium salt, followed by
Some of the catalysts are expensive, complex or
base treatment to give an ylide, and subsequent reac- poorly available and reactions are performed in the
tion with carbonyl compounds to give olefinic prod- homogenous conditions, which contaminates the
ucts, with a one-pot synthesis. a,b-Unsaturated esters products and restricts use in industry. As a result of
are obtained directly in one pot in good yields by the the increased environmental consciousness in chemi-
reaction of an aldehyde with methyl bromoacetae cal research and industry, efforts are now directed to-
using n-Bu3P/Zn at 1008C[5] with catalytic amounts of wards heterogenization. We reported earlier on the
tributylarsine or dibutyl telluride[6] or PEG-supported WWE reaction by using the heterogeneous solid base
telluride[7] in the presence of triphenyl phosphite in catalysts Mg-Al-hydrotalcite-O-t-Bu and NAP-
stoichiometric amounts. Other reports[8] include the MgO.[11]
use of ethyl diazoacetate (EDA) instead of a-bromo
Nanocrystalline metal oxides[12a,b] have been effi-
esters in the above protocol by using catalytic ciently used as absorbents for gases and destruction
amounts of iron, ruthenium, or cobalt porphyrin com- of hazardous chemicals and as catalysts for organic
plexes or ruthenium and rhenium complexes in the transformations.[11b,12c–g] These high reactivities are due
presence of PPh3, PACHTREU(GN OMe)3, PAHCTRE(UGN OEt)3 or other PPh2R to high surface areas combined with unusually reac-
Adv. Synth. Catal. 2006, 348, 1977 – 1985
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1977

Boyapati M. Choudary et al.
FULL PAPERS
tive morphologies. Herein, we report an effective
one-pot Wittig reaction to afford a,b-unsaturated
esters and nitriles in excellent yields with high E-ste-
reoselectivity by using nanocrystalline magnesium
oxide catalyst (NAP-MgO) (Scheme 1).
Results and Discussion
Various magnesium oxide crystals [commercial MgO,
CM-MgO (SSA: 30 m2 gÀ1), conventionally prepared
MgO, NA-MgO (SSA: 250 m2 gÀ1), aerogel prepared
MgO, NAP-MgO (SSA: 590 m2 gÀ1)] were initially
evaluated in the Wittig reaction with benzaldehyde,
ethyl bromoacetate and PPh3 at room temperature in
order to understand the relationship between struc-
ture and reactivity. All these MgO crystals catalyze
the Wittig reaction in quantitative yields. However,
the nanocrystalline MgO (NAP-MgO) was found to
be more active than NA-MgO and CM-MgO in the
Wittig reaction (Table 1).
In the studies regarding the effect of various sol-
vents, the reaction was conducted between benzalde-
hyde and ethyl bromoacetate, in the presence of tri-
phenylphosphine and NAP-MgO with different sol-
vents like toluene, acetonitrile, THF, 1,4-dioxane, tol-
uene/DMF (1:1), methanol and DMF (Table 2). When
we take DMF alone as a solvent at room temperature,
the desired olefin could be obtained in quantitative
yields with excellent stereoselectivity. In all the other
solvents, the olefinated product was isolated in low
yields. In methanol, the olefinated product was ob-
tained quantitatively, but with poor stereoselectivity
compared to the reaction conducted in DMF
(Table 2, entry7). Therefore, we conclude that DMF is
a suitable solvent for this reaction. We have also
Scheme 1. NAP-MgO-catalyzed Wittig reaction between al-
dehydes and a-halo esters or nitriles.
Table 1. Wittig reaction between benzaldehyde and ethyl
bromoacetate/PPh3 with various catalysts[a]
.
Entry
Catalyst
Time [h]
Yield [%][b]
E/Z[c]
1.
2.
3.
4.
5.
NAP-MgO
NA-MgO
CM-MgO
Sil-NAP-MgO
Sil-NA-MgO
8
96
95
94
92
90
99:1
99:1
97:3
99:1
99:1
17
23
18
32
[a]
Reaction conditions: benzaldehyde (1 mmol), ethyl bro-
moacetate (1 mmol), PPh3 (1 mmol), catalyst (0.075 g),
DMF (5 mL) at room temperature.
[b]
[c]
Isolated yield.
The ratio of E:Z isomers was determined by 1H NMR
spectroscopy of the crude reaction mixture.
Table 2. Optimization of Wittig reaction of benzaldehyde
with ethyl bromoacetate/PPh3 catalyzed by NAP-MgO[a]
.
Entry Solvent
Time [h] Yield [%][b] E/Z[c]
1.
2.
3.
4.
5.
6.
7.
Toluene
Toluene/DMF (1:1) 15
2[d]
–
–
74
96
90
86
84
94
99:1
99:1
99:1
98:2
99:1
84:16
DMF
8
tested different organic [PACHTERNGU(OPh3), PACHTRE(UNG OMe3)] and inor-
ganic [NaHSO3, Na2SO3] reducing agents under the
same reaction conditions, but all are inactive.
Acetonitrile
THF
1,4-Dioxane
Methanol
17
18
20
8
To determine the generality of this reaction, a vari-
ety of structurally different aldehydes with different
a-halo esters including methyl, ethyl, tert-butyl substi-
tuted ones and a-bromoacetonitrile were employed
and the results are summarized in Table 3. It was
found that aliphatic, aromatic and heterocyclic alde-
hydes afforded good to excellent yields with high ste-
reoselectivity. As expected the rate of the reaction is
[a]
Reaction conditions: benzaldehyde (1 mmol), ethyl bro-
moacetate (1 mmol), PPh3 (1 mmol), catalyst NAP-MgO
(0.075 g), solvent (5 mL) at room temperature.
Isolated yield.
[b]
[c]
The ratio of E:Z isomers was determined by 1H NMR
spectroscopy of the crude reaction mixture.
[d]
In toluene after 2 h, the catalyst sticks to the flask walls.
Table 3. Wittig reaction of different aldehydes with various a-halo esters and bromoacetonitrile catalyzed by NAP-MgO[a]
.
Entry
Aldehyde 1
Substrate 2
Time [h]
Yield of 3 [%][b]
E/Z[c]
1
2
3
4
5
C6H5-
2a
2b
2c
2d
2e
8
96
94
96
92
90
99:1
99:1
50:50
98:2
99:1
10
14
26
28
1978
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Adv. Synth. Catal. 2006, 348, 1977 – 1985

Facile Synthesis of a,b-Unsaturated Esters and Nitriles
Table 3. (Continued)
FULL PAPERS
Entry
Aldehyde 1
Substrate 2
Time [h]
Yield of 3 [%][b]
E/Z[c]
6
7
8
9
C6H5
4-NO2C6H4-
2f
32
90
98, 95[d], 98[e]
97
97
96
95
92
96
94
98
96
96
94
94
89
86
88
86
89
88
92
94
94
96
76
79
91
88
92
82
86
93
94
90
93
95
92
91
94
90
96
83
88
81
88
91
82
86
96:4
99:1
99:1
36:74
96:4
99:1
99:1
96:4
96:4
99:1
99:1
23:77
99:1
99:1
99:1
99:1
99:1
99:1
44:56
98:2
99:1
99:1
99:1
99:1
99:1
99:1
99:1
99:1
55:45
99:1
99:1
92:8
91:9
99:1
99:1
48:52
99:1
99:1
99:1
99:1
99:1
99:1
99:1
99:1
99:1
95:5
99:1
99:1
2a
2b
2c
2d
2a
2b
2a
2a
2a
2b
2c
2a
2b
2a
2b
2a
2b
2c
2d
2a
2b
2a
2b
2a
2b
2a
2b
2c
2a
2b
2a
2b
2a
2b
2c
2d
2a
2b
2a
2b
2a
2b
2a
2b
2d
2a
2b
3, 3[d], 3[e]
4
9
20
4
9
3
4
4
4
9
7
9
12
12
14
16
18
32
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
4-ClC6H4-
2-NO2C6H4-
2-ClC6H4-
3-CNC6H4-
4-COOHC6H4-
4-CH3C6H4-
4-CH3OC6H4-
3,4-Cl2C6H3-
5
3
3
4-CF3C6H4-
4-BnO,3-MeOC6H3-
2-naphthyl-
16
20
10
8
12
12
10
4
3
6
5
10
24
8
6
3
3
10
8
11
10
20
11
11
trans-C6H4CH=CH-
1-(2-Br)-piperanyl
2-furfuryl-
2-pyridyl
2-(1-Me)-imidazolyl
cyclohexyl-
CH
3A
CH3CHACTHER(UNG CH3)CH2-
54[f]
2a
2b
5
4
90
86
99:1
99:1
55
[a]
Reaction conditions: aldehyde (1 mmol), a-halo ester or bromoacetonitrile (1 mmol), PPh3 (1 mmol), catalyst NAP-MgO
(0.075 g), DMF (5 mL) at room temperature.
[b]
[c]
[d]
[e]
[f]
Isolated yield.
The ratio of E:Z isomers was determined by 1H NMR spectroscopy of the crude reaction mixtures.
2nd cycle.
4th cycle.
PMB=p-methoxybenzyl.
Adv. Synth. Catal. 2006, 348, 1977 – 1985
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1979

Boyapati M. Choudary et al.
FULL PAPERS
Table 4. Synthesis of a-fluoro-a,b-unsaturated esters by
faster with benzaldehydes having electron-withdraw-
ing groups than the substrates bearing an electron-do-
nating group. Aromatic aldehydes with electron-with-
drawing groups in any position on aromatic ring gave
excellent yields (entries 7–19, 26–29). Electron-donat-
ing group containing aromatic aldehydes gave good
yields (entries 20–25). Highly conjugated aromatics
like naphthaldehyde and cinnamaldehyde (entries 32–
36), heteroaromatic aldehydes (entries 39–46) and ali-
phatic aldehydes (entries 47–53) afforded good yields.
When we did the reaction with a vanillin derivative
(entries 30, 31) moderate yields were obtained, which
might be due to bulky and electron-donating groups
on the aromatic ring. g,d-Epoxy-a,b-unsaturated
esters, useful building blocks, could also be synthe-
sized by the current method in good yields with excel-
using NAP-MgO.[a]
Entry Aldehyde (R)
Time [h] Yield [%][b] E/Z[c]
1.
2.
3.
4.
C6H5- (a)
4-NO2C6H4- (b)
4-CH3OC6H4-(c) 48
3-CNC6H4- (d) 36
40
36
56
69
42
67
10:90
29:71
9:91
16:84
[a]
Reaction conditions: Aldehyde (1 mmol), ethyl bromo-
fluoroacetate (1 mmol), PPh3 (1 mmol), catalyst NAP-
MgO (0.075 g), DMF (5 mL) at room temperature.
Isolated yield.
[b]
[c]
The ratio of E:Z isomers was determined by 19F NMR[14b]
spectroscopy of the crude reaction mixtures.
lent stereoselectivity (entries 54 and 55). In most of group than with substrates bearing electron-donating
these a,b-unsaturated esters, the traditional E-stereo- groups.
selectivity was maintained, compared with typical
In our mechanistic studies, there was no reaction
Wittig reactions of stabilized ylides. But a substituent between benzaldehyde and ethyl bromoacetate on
at the ortho-position of an aromatic aldehyde shows using NAP-MgO in the absence of PPh3, whereas
little difference in stereoselectivity (entries 13, 14, 37, only 5% conversion was observed in the presence of
38) that might be due to an ortho steric effect. In the PPh3 without NAP-MgO. These results indicate that
reaction between aldehyde and a-chloro esters, the both PPh3 and NAP-MgO are essential for this reac-
olefinated product (entries 4, 5, 6, 10, 25, 42, 51) was tion. So, it can be assumed that PPh3 reacts with ethyl
obtained quantitatively, with high stereoselectivity in bromoacetate via an SN2 mechanism forming a phos-
longer reaction times compared to a-bromo esters, phonium ylide, which immediately attacks the benzal-
which might be due to the difference in electronega- dehyde carbonyl carbon and forms an oxaphosphe-
tivity between chlorine and bromine. We have also tane intermediate, then by eliminating the Ph3P=O, it
prepared a,b-unsaturated nitriles by this method in forms an olefin (Scheme 3). In these steps, MgO ef-
excellent yields (entries 3, 9, 17, 24, 34, 41) but with fectively catalyzed and accelerated the formation of
poor stereoselectivity. The increase in Z-isomer is due the phosphonium ylide and the olefination reactions.
to the lower steric requirements of the linear cyano To confirm this, ethyl bromoacetate and PPh3 were
group.
stirred with catalyst the NAP-MgO in DMF over-
A fluorine atom substitution, adjacent to the ester night, and then the catalyst was filtered. To this fil-
moiety, increases significantly the biological activity trate, benzaldehyde was added and the misxture was
of these compounds, as exemplified in vitamin A and stirred for 20 h but only a 50% yield was obtained.
pheromone chemistry.[4a] We have also synthesized a- There is only 5% conversion in the reaction between
fluoro-a,b-unsaturated esters (5) (Scheme 2, Table 4), benzaldehyde and ethyl bromoacetate/PPh3 without
a useful class of intermediates in the synthesis of a va- using NAP-MgO. In another reaction, the pre-preÀ-
+
riety of biologically active fluoro compounds such as pared phosphonium salt[26] Ph3P CH2 COOEtBr
retinoids, insect sex pheromones, and pyrethroids[13,4c] was reacted with benzaldehyde in DMF, and stirred
through a Wittig reaction under these optimized con- with and without the catalyst. It was observed that in
ditions in moderate yields[14a] with Z-selectivity the presence of catalyst, after 20 h, the olefinated
(Scheme 2, Table 4). The rate of the reaction is faster product was obtained quantitatively, but in the ab-
with a benzaldehyde having an electron-withdrawing sence of catalyst, even after 24 h, only 5% product
was obtained. Therefore, it can be concluded that
À
À
MgO catalyzes this reaction.
This is further substantiated by 31P NMR studies. In
the absence of both aldehyde and catalyst, formation
of the phosphonium salt was observed. But when the
same reaction was performed without aldehyde but in
the presence of catalyst, formation of phosphonium
salt and phosphonium ylide were observed. To ad-
dress this issue, we conducted three experiments.
In the first experiment, ethyl bromoacetate and tri-
phenylphosphine were stirred in DMF without alde-
Scheme 2. Wittig reaction of various benzaldehydes with
ethyl bromofluoroacetate by using NAP-MgO.
1980
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Facile Synthesis of a,b-Unsaturated Esters and Nitriles
FULL PAPERS
Scheme 3. The plausible mechanism for the Wittig reaction catalyzed by NAP-MgO.
hyde and catalyst. Within 30 min, triphenylphosphine 15 h there is a decrease in the intensity of the phos-
had completely disappeared (followed by TLC) and phonium salt peak and a simultaneous increase in the
formation of phosphonium salt Ph3P+CH2COOEtBrÀ intensity of phosphonium ylide peak in the 31P NMR
was observed via SN2 mechanism. This was confirmed spectra. The phosphonium salt was not completely
by the observed peak at d=20.987 (lit.[15] d=20.5) in converted into the phosphonium ylide even after 24 h,
the 31P NMR spectrum shown in Figure 1 of the Sup- so there may be an equilibrium between phosphoni-
porting Information. In the second experiment, ethyl um salt and ylide. Along with these phosphonium salt
bromoacetate and triphenylphosphine were stirred in and ylide peaks, two more peaks are observed at d=
DMF without aldehyde but in the presence of the cat- 22.1–22.4 and d=16.1–16.3. We assume that these
alyst, NAP-MgO, after 1 h there is no phosponium peaks also could be due to the salt (d=22.1–22.4) and
ylide peak; instead we observed the phosphonium salt the ylide (d=16.1–16.3), which are co-ordinated with
peak at d=20.88 and another peak at d=22.23 in the catalyst.[15,16] This is further confirmed by the addi-
31P NMR spectrum. The reaction was continued and tion of the aldehyde (4-nitrobenzaldehyde) to the re-
samples were withdrawn periodically after 2 h, 6 h, action mixture after 24 h, which gave the desired
9 h, 12 h, 15 h and they showed peaks in the regions product and the phosphine oxide at d=29.26 (lit.[17]
1
d=17.8–17.9 and 20.8–20.9 corresponding to phospho- d=30.2), as observed in H and 31P NMR spectra, re-
nium ylide, Ph3P=CHCOOEt {lit.[15]: d17.9} and the spectively, and those two peaks at d=22.1–22.4 and
phosphonium salt, Ph3P+CH2COOEtBrÀ (lit.[15] d= d=16.1–16.3 had disappeared in 31P NMR spectrum
20.5}, respectively (see Figures 3–7 in the Supporting (see Figure 9 in the Supporting Information). Thus,
Information). On increasing the reaction time, i.e., 2– the entire phosphonium salt was completely convert-
Adv. Synth. Catal. 2006, 348, 1977 – 1985
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1981

Boyapati M. Choudary et al.
FULL PAPERS
Scheme 4. The plausible mechanism for the stereoselective E-a,b-unsaturated esters and Z-a-fluoro,a,b-unsaturated esters in
Wittig reaction catalyzed by NAP-MgO.
ed into the phosphonium ylide which, on interaction a complex with the unsaturated Mg+ site (Lewis acid
with the aldehyde, gave the product and phosphine type) of NAP-MgO. The Lewis acid moiety (Mg2+/
oxide. In the third experiment, ethyl bromoacetate Mg+) of the catalyst co-ordinates with OÀ of the alde-
and triphenylphosphine were stirred in DMF with 4- hyde carbonyl oxygen and carbonyl oxygen of ylide
nitrobenzaldehyde in the presence of the catalyst, ester moiety of the betaine intermediate[20,21]
NAP-MgO, and after 3 h, we observed only one (Scheme 3 and Scheme 4). In the betaine, thealdehyde
peak[18] at d=29.67 (lit.[17] d=30.2) corresponding to R group and the ylide COOEt group should be in dif-
triphenylphosphine oxide in the 31P NMR spectrum ferent planes for minimizing their steric interac-
1
and the product in the H NMR spectrum while there tions.[22] Therefore, a trans-oxaphosphetane will be
are no peaks at d=22.1–22.4 and d=16.1–16.3 in the formed by the planar four-centered transition state to
31P NMR spectrum (see Figure 10 in the Supporting relieve a dominating 1,2 interaction between the R
Information).
group on the aldehyde and the COOEt group on the
The phosphonium ylide peak appears at a higher ylide, which predominates to give E-a,b-unsaturated
magnetic field than that of the phosphonium salt in esters[2a,23] (Scheme 3 and Scheme 4). When the hy-
the 31P NMR spectrum. This fact may be attributed to drogen is substituted by a fluorine atom in the same
a lower positive charge on the phosphorus atom in E-form of the a,b-unsaturated ester, the product a-
the ylide than that in the phosphonium salt.
fluoro-a,b-unsaturated ester is considered as the Z-
The carbanionoid carbon of the ylide attacks the form according to the atomic number priority and the
electrophilic carbon of the carbonyl group of alde- same Z-isomer of the fluoro compound was predomi-
hyde with the formation of a betaine, which in turn nantly obtained under our optimized conditions
drives the formation of a very strong phosphorus- (Scheme 2 and Scheme 4, Table 4) (see Figures 11–14
oxygen bond, a four-membered cyclic transition state in the Supporting Information). Thus, a similar con-
“oxaphosphetane”, which collapses into the olefin densation holds good for a,b-unsaturated esters (E-
and Ph3P=O (Scheme 3).
form) and a-fluoro-a,b-unsaturated esters (Z-form),
Generally, the stereochemistry of the Wittig reac- as their basic structure is unaltered except for the flu-
tion is influenced by the presence of p-acceptor orine substitution as can be seen in Scheme 4. In con-
groups at the a-carbon. Resonance-stabilized ylides, trast, in a,b-unsaturated nitriles, the increase in Z-
bearing a p-acceptor group at the a-carbon, react isomer is due to the lower steric requirement of the
with aldehydes to give almost exclusively E-olefins, linear cyano group. Due to the above described rea-
where as non-stabilized ylides, bearing an a-alkyl sons, i.e., the formation of a “betaine” intermediate
group afford Z-olefins.[2a] In the Wittig reaction using which forms a complex with the unsaturated Mg+ site
NAP-MgO, olefins are obtained with high selectivity (Lewis acid type) of MgO, we obtained almost the
towards the E-isomer which is due to the surface of same selectivity of a,b-unsaturated esters in various
the catalyst and its highly reactive sites.[12c,19] Here we reactions with different MgO crystallites CM-MgO,
assume that the formed intermediate “betaine” forms NA-MgO, Sil-NA-MgO and Sil-NAP MgO (Table 1).
1982
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Facile Synthesis of a,b-Unsaturated Esters and Nitriles
FULL PAPERS
To understand the relationship between structure ported soluble PEG-supported telluride as an effec-
and reactivity of the catalyst in detail, we need to tive catalyst for the Wittig-type reaction to give a va-
know the structure and nature of the reactive sites of riety of a,b-unsaturated esters. The catalyst was re-
NAP-MgO. NAP-MgO has a single-crystallite, three- covered quantitatively, but in the second run only a
dimensional polyhedral structure, which shows the 69% yield was obtained.[7] Sun and Kühn reported
presence of high surface concentrations of edge/ the olefination of aldehydes with ethyl diazoacetate in
corner and various exposed crystal planes (such as the presence of PPh3 catalyzed by a ClFeTPP porphy-
002, 001, 111), which leads to an inherently high sur- rin complex in an ionic liquid [bmim] PF6. The cata-
face reactivity per unit area. Thus, NAP-MgO indeed lyst was reusable with an 88% yield in the 2nd cycle.[8a]
displayed the highest activity compared to NA-MgO
and CM-MgO. Besides this, the NAP-MgO has Lewis
acid sites, Mg2+, Lewis basic sites O2À and OÀ, lattice- Conclusions
bound and isolated Brønsted hydroxy groups and
anionic and cationic vacancies.[12c,19] Wittig reactions In summary, nanocrystalline MgO was found to be an
are known to be driven by base catalysts[23,24] and, ac- effective heterogeneous catalyst for the one-pot
cordingly, the surface -OH, O2À sites of these oxide Wittig reaction to afford a,b-unsaturated esters and
crystals are expected to trigger these reactions. To ex- nitriles in excellent yields with high E-stereoselectiv-
amine the role of -OH, Sil-NA-MgO and Sil-NAP- ity in the presence of triphenylphosphine. To con-
MgO,[12c] devoid of free -OH, were tested in Wittig re- clude, the simplicity of our procedure, the mildness of
actions. It is found that the silylated MgO samples the reaction conditions, the excellent yields, the high
had longer reaction times than the corresponding stereoselectivity, together with capacity for easy sepa-
MgO samples in the Wittig reaction (Table 1). Al- ration of reaction mixture, especially the reusability
though both NAP-MgO and NA-MgO possess de- of the catalyst, demonstrates our method to be practi-
fined shapes and the same average concentrations of cal for the synthesis of a,b-unsaturated esters and ni-
surface -OH groups, a possible rationale for higher re- triles.
activity to a,b-unsaturated esters and nitriles by the
NAP-MgO is that -OH groups present on the edge
and corner sites on the NAP-MgO, which are stretch-
ed in three-dimensional space, are more isolated and
accessible for the reactants. NAP-MgO has a single
Experimental Section
crystallite polyhedral structure with the presence of
high surface concentrations of edge/corner and vari-
ous exposed crystal planes (such as 002, 001, 111),
which leads to inherently high surface reactivity per
unit area. Thus, NAP-MgO indeed displayed the high-
est activity compared to NA-MgO and CM-MgO. In
the Wittig reaction, O2À/OÀ sites of NAP-MgO ab-
stract an acidic proton of the Ph3P+-CH2-COOEtBrÀ
(PPh3 reacts with ethyl bromoacetate via an SN2
mechanism), giving a carbanion, which forms a com-
plex with the unsaturated Mg+ site (Lewis acid type)
of NAP-MgO. The Wittig reaction proceeds via dual
activation of both substrates (nucleophiles and electo-
philes) by NAP-MgO. Thus, the Lewis base (O2À/OÀ)
of the catalyst activates Ph3P+-CH2-COOEtBrÀ, and
the Lewis acid moiety (Mg2+/Mg+) activates the car-
General Remarks
Nanocrystalline MgO samples were obtained from Nano-
Scale Materials Inc., Manhattan, Kansas, USA. All catalysts
are calcined at 4008C for 4 h before use. All chemicals were
purchased from Aldrich Chemicals and S.D Fine Chemicals,
Pvt. Ltd. India and used as received. All LR grade solvents
were used as received from S.D Fine Chemicals, Pvt. Ltd.
India. ACME silica gel (100–200 mesh) was used for column
chromatography and thin layer chromatography was per-
formed on Merck precoated silica gel 60-F254 plates. The
1H NMR spectra were recorded on
200 MHz or Bruker-Avance 300 MHz spectrometer.
a Varian-Gemini
a
Chemical shifts (d) are reported in ppm, using TMS (d=0)
as an internal standard in CDCl3. 31P NMR spectra were re-
corded on a Varian-Unity 400 MHz spectrometer. Chemical
bonyls of the aldehyde and the ylide ester (Scheme 3 shifts (d) are reported in ppm, using 85% H3PO4 as an ex-
ternal standard in CDCl3. The 19F NMR spectra were re-
and Scheme 4).[20]
corded on a Varian-Unity 400 MHz spectrometer. The E/Z
The catalyst was reused for 4 cycles without loss of
activity (entry 7, Table 3). In the 2nd cycle, a 95%
yield was obtained. After the 3rd cycle, the catalyst
was calcined at 2508C for 1 h under a nitrogen flow
and reused and the desired product was obtained in
98% yield. Sychev et al. reported that hydrotalcites
efficiently catalyzed the liquid phase synthesis of al-
kenes in the Wittig reaction, but they did not specify
1
ratio was determined from H NMR and 19F NMR spectra
using coupling constant (J) values. All the liquid secondary
ion mass spectrometric (LSI-MS) experiments were carried
out using an Autospec M (Micromass, Manchester, UK)
mass spectrometer of EBE geometry, equipped with an
OPUS V3.1X data system. A 2.2 mA primary beam of
cesium ions accelerated to 25 keV and the ion source was
operated at an acceleration voltage of 8 kV to effect ioniza-
the reusability of the catalyst.[25] Yong Tong et al., re- tion.
Adv. Synth. Catal. 2006, 348, 1977 – 1985
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
1983

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Acknowledgements
We wish to thankthe CSIR for financial support under the
TaskForce Project COR-0003. K. M and K. V. S. R thank
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1985