Bifunctional catalysts stabilized on nanocrystalline magnesium oxide for one-pot synthesis of chiral diols

Article abstract of DOI:10.1002/adsc.200404112

New bifunctional catalysts composed of PdCl₄^2-, OsO₄^2- and OsO₄^2-, WO ₄^2- designed and prepared by a counterionic stabilization technique involving the reactions of Na₂PdCl₄-K ₂OsO₄ and K₂OsO₄-Na ₂WO₄ with nanocrystalline MgO are well characterized. These bifunctional catalysts, NAP-Mg-PdOs and NAP-Mg-OsW perform tandem Heck asymmetric dihydroxylation and asymmetric dihydroxylation-N-oxidation reactions, respectively, in the presence of the chiral ligand 1,4-bis(9-o- dihydroquinidinyl)phthalazine [(DHQD)₂PHAL] in a single pot. It is quite impressive to note that H₂O₂ is used as a terminal oxidant to provide N-methylmorpholine N-oxide (NMO) in situ by the oxidation of N-methylmorpholine (NMM) in the asymmetric dihydroxylation-N-oxidation catalyzed by NAP-Mg-OsW.

Full text of DOI:10.1002/adsc.200404112

FULL PAPERS
Bifunctional Catalysts Stabilized on Nanocrystalline Magnesium
Oxide for One-Pot Synthesis of Chiral Diols
Boyapati M. Choudary,* Karangula Jyothi, Moumita Roy, Mannepalli L. Kantam,
Bojja Sreedhar
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: (þ91)-40-2716-0921,e-mail: choudary@iict.res.in
Received: April 17, 2004; Accepted: August 20, 2004
Abstract: New bifunctional catalysts composed of quinidinyl)phthalazine [(DHQD)2PHAL] in a single
2À
2À
PdCl42À, OsO4 and OsO42À, WO4 designed and pot. It is quite impressive to note that H2O2 is used
prepared by a counterionic stabilization technique as a terminal oxidant to provide N-methylmorpholine
involving the reactions of Na2PdCl4-K2OsO4 and N-oxide (NMO) in situ by the oxidation of N-methyl-
K2OsO4-Na2WO4 with nanocrystalline MgO are well morpholine (NMM) in the asymmetric dihydroxyla-
characterized. These bifunctional catalysts, NAP- tion-N-oxidation catalyzed by NAP-Mg-OsW.
Mg-PdOs and NAP-Mg-OsW perform tandem Heck
asymmetric dihydroxylation and asymmetric dihy- Keywords: asymmetric synthesis; bifunctional cataly-
droxylation-N-oxidation reactions, respectively, in sis; chiral diols; counterionic stabilization; nanocrys-
the presence of the chiral ligand 1,4-bis(9-o-dihydro- talline magnesium oxide
Introduction
ployed to address the issue of complete recovery of os-
mium from the reaction medium.
The performance of multistep syntheses in one pot,
An interesting development was made by Bäckvall
prevalent in biosystems, is an attractive strategy to im- et al. in realizing the higher economical process by using
prove the efficiency of organic processes in terms of H2O2, the stoichiometric oxidant, and N-methylmorpho-
conservation of energy, lowering the process time and line (NMM) in catalytic amounts to continuously gener-
inventory of equipment and minimizing the use of ate N-methylmorpholine N-oxide (NMO) in situ via oxi-
chemicals and the production of waste.[1] Significant dation using biomimetic flavin[7a, b] or vanadyl acetylace-
progress using a combination of two catalysts for ef- tonate[7c] as the electron transfer mediator in a multicom-
fecting tandem reactions has been achieved.[2] The re- ponentcatalyticsystemfortheADreactionofolefins.We
cent design of a single matrix bifunctional catalyst com- demonstrated the reoxidation of NMM to facilitate con-
prising a BINOL-BINOP copolymer for the tandem tinuous in situ production of NMO to sustain the Os(VI)/
asymmetric diethylzinc addition and hydrogenation Os(VIII) catalytic cycle induced by a bifunctional heter-
of acetylbenzaldehydes marks a new era in bifunctional ogeneous catalyst composed of osmium and tungsten ox-
catalysis.[3]
ides on the single matrix using H2O2 as the terminal oxi-
The Sharpless catalytic asymmetric dihydroxylation dant.[5c] Recently, we immobilized osmium tetroxide on
(AD) of olefins, an inspiring invention, provides the nanocrystalline MgO by the counterionic stabilization
most elegant method for the preparation ofchiral vicinal technique for achiral dihydroxylation.[8] We now report
diols.[4a–d] Chiral vicinal diol units are often observed as the design and development of new bifunctional hetero-
key structures of natural products and are also used in geneous catalysts composed of palladium/osmium and
the synthesis of chloramphenical (broad-spectrum anti- osmium/tungsten systems on the nanocrystalline MgO
biotic), diltiazem hydrochloride (calcium channel matrix and the performance of Heck-AD and N-oxida-
blocker), the taxol side chain, macrocyclic antitumor tion-AD reactions using H2O2 as the terminal oxidant.
drugs and b-lactams. Although the AD reaction offers
The nanocrystalline metal oxides, MgO, CaO, Al2O3
a number of processes that could be applied to the syn- and ZnO are porous inorganic solids in the 4–7 nm parti-
thesis of pharmaceuticals, fine chemicals, etc., the high cle size range, which make up a new realm of matter in
cost, toxicity and possible contamination of osmium cat- which physical and chemical properties change as size
alysts in the products restrict its use in industry. Hetero- changes. Furthermore, these solids can exist with numer-
genization of OsO4 via microencapsulation,[4e–h] an ion- ous surface sites with enhanced surface reactivity such as
exchange technique,[5] and covalent anchoring[6] is em- crystal corners, edges or ion vacancies.[9] Nanocrystalline
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DOI: 10.1002/adsc.200404112
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Boyapati M. Choudary et al.
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metal oxides have attracted great attention due to their could be stabilized by forming adducts with the reac-
unusual magnetic, optical, physical and surface chemical tive-accepting surface sites on the MgO. In an effort to
2À
and catalytic properties.[10–16] These nanoporous materials obtain counterionic stabilization of PdCl42À, OsO4
2À
are mainly used as efficient destructive chemisorbents for and WO4 with Mg2þ of the MgO, commercially avail-
toxic gases, NO2, SO2, SO3 and HCl, as well as chlorinated able CM-MgO [surface area (SA) 30 m2/g], convention-
and phosphorus-containing compounds.[11] Nanocrystal- ally prepared NA-MgO (SA 250 m2/g) and aerogel pre-
line MgO is found to be very active in the dehydrohaloge- pared NAP-MgO (SA 600 m2/g) were treated with
nation of chlorohydrocarbons at high temperatures.[12] Na2PdCl4, K2OsO4 and Na2WO4 to afford the samples
Due to the high surface area, these nanostructured solid of Mg-OsO4, Mg-PdCl4-OsO4 (Mg-PdOs), and Mg-
materials exhibit high activity. The reactivity of these ma- OsO4-WO4 (Mg-OsW). The preparation and character-
terials is further enhanced by depositing very thin layers of ization of NAP-Mg-OsO4 catalyst was reported in
transition metal oxides on the crystallites of MgO.[17] The our earlier communication.[8] In the reaction with
presence of edge-corner and other defect sites allow the NAP-MgO, (SA 600 m2/g) the entire amounts of
nanostructured MgO materials to possess a high concen- Na2PdCl4, K2OsO4 and Na2WO4 used were consumed.
tration of reactive surface ions. The reactive sites on the On the other hand, a small amount each (<0.3%) of pal-
surface of MgO are as follows:[18] 1) Mg2þ site, which is ladate, osmate and tungstate was detected in the treated
of the Lewis acid type, 2) O2À site which is of the Lewis samples of CM-MgO and NA-MgO. During the prepa-
base type, 3) lattice bound and isolated hydroxyl groups, ration of the catalyst, which involves the reaction with
and 4) anionic and cationic vacancies. The presence of cor- Na2PdCl4, K2OsO4 and Na2WO4, the Naþ, Kþ ions will
ner and edge sites on the surface of NAP-MgO (aerogel interact with the OxÀ sites/anionic vacancies. The
2À
2À
prepared) could approach 20% while on NA-MgO (con- PdCl42À, OsO4
and WO4
will interact with the
ventionally prepared) it is less than 0.5% and on CM- Mg2þ sites/cationic vacancies present on corner or
MgO (commercially prepared) essentially 0%.[19] For ex- edge of nanocrystalline NAP-MgO to form bifunctional
ample, an edge, or even more so, a corner O2À anion is co- catalysts as described (Scheme 1) for the synthesis of
ordinatively unsaturated and is seeking Lewis acids (elec- chiral diols successfully in a single pot.
tron-deficient species) to help stabilize and delocalize its
negative charge. Conversely, an Mg2þ ion on an edge or
corner is seeking Lewis bases (electron-rich species) to Characterization of Nanocrystalline MgO-Supported
stabilize and delocalize its positive charge. Therefore, Catalysts
these coordinatively unsaturated O2À and Mg2þ ions read-
ily accept incoming reagents with Lewis acid or Lewis base All the catalysts developed were well characterized by
character. The excess positive charge will always be satis- FTIR, SEM-EDAX and XPS. In the FTIR spectra of
fied with an anion deficiency and therefore the structure these counterionic stabilized catalysts, broad absorption
will not loose its anion exchange capacity during the reac- bands appear near 815–860 cmÀ1, which are assigned to
¼ ¼
tion. The best example is that nano-MgO can absorb up to the vibrational asymmetric O M O (M¼Os and/or W)
13% by weight of Cl2 in the reaction with chlorine gas at stretching unlike the sharp bands observed at 819 cmÀ1
room temperature and atmospheric pressure.[20]
in the case of potassium osmate and at 831, 857 cmÀ1 in
the case of sodium tungstate spectra. The observation of
broad bands in the same region for the catalysts indi-
cates that the osmate and tungstate are unaffected
upon counterion stabilization onto the support, while
experiencing very weak interactions with the support
(Figure 1a). During the preparation of these catalysts,
the surface of NAP-MgO was hydroxylated as indicated
Results and Discussion
Preparation of Crystalline MgO-Supported Catalysts
This situation presents an opportunity to prepare new by non-H-bonded OH groups at 3715 cmÀ1 in the IR
and unusual materials, wherein the highly reactive ions (Figure 1b). This is consistent with the reactive profile
Scheme 1. Preparation of NAP-MgO supported bifunctional catalysts.
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Table 1. XPS binding energies for NAP-MgO supported cat-
alysts.
Catalyst
Pd
Os
W
3d5/2
3d3/2
4f7/2 4f5/2 4f7/2 4f5/2
54.0 56.5
NAP-Mg-OsO4
NAP-Mg-PdOs[a] 336.9 342.3 54.6 57.0
NAP-Mg-PdOs[b] 337.0 341.9 54.2 56.8
NAP-Mg-OsW[a]
NAP-Mg-OsW[b]
–
–
–
–
54.5 57.0 35.5 37.5
54.4 57.0 35.0 37.2
[a]
Fresh catalyst.
Used catalyst.
[b]
of NAP-MgO with water.[21] The surface of the nano-
MgO is only hydroxylated to Mg(OH)n, and it takes a
longer time and heating to transform the bulk nano-
MgO. The XRD of the NAP-Mg-OsO4, NAP-Mg-
PdOs, NAP-Mg-OsW samples also indicate the forma-
tion of Mg(OH)n during the preparative protocol (Fig-
ure 2).[22] The SEM-EDX (scanning electron micros-
copy-energy dispersive X-ray analysis) of NAP-Mg-
OsO4, NAP-Mg-PdOs and NAP-Mg-OsW shows the
presence of metals – 8.96% (Os), 3.98% (Pd), 7.15%
(Os) and 7.04% (Os), 6.81% (W) in the respective sam-
ples. The X-ray photoelectron spectroscopic (XPS) re-
sults of the fresh and used bifunctional NAP-Mg-PdOs
and NAP-Mg-OsW catalysts show almost identical
[25]
binding energies for Pd,[23] Os,[24] and W
(Table 1).
This confirms that the oxidation states of the respective
Figure 1. a FTIR spectra of NAP-MgO-supported catalysts. b metals remain static during the counterionic stabiliza-
During the preparation of NAP-MgO-supported catalysts,
the surface of NAP-MgO was hydroxylated as indicated by
non-H bonded OH groups at 3715 cmÀ1 in the IR.
tion process and at the end of the reaction.
All these results ruled out the formation of bimetallic
species. All these studies indicate the retention of the co-
ordination geometries of the specific divalent anions
Figure 2. The XRD of the a NAP-MgOsO4, b NAP-Mg-PdOs, and c NAP-Mg-OsW catalysts.
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Table 2. Asymmetric dihydroxylation of olefins with NAP-
Mg-OsO4.
Table 3. Influence of additive and slow addition of olefin on
the ee in the AD reaction of methyl cinnamate.
Entry
Olefin
Isolated
yield [%]
ee [%][a]
Abs.
Entry Catalyst
Additive Slow
addition [h]
ee [%]
config.[b]
1
2
85
91
99
77
RR
R
1
2
3
4
K2OsO4 ·2 H2O
NAP-Mg-OsO4
NAP-Mg-OsO4
–
–
–
–
–
12
88
45
94
95
NAP-Mg-OsO4 Et3N·HI 12
3
4
90
96
80
94
R
2S,3R
It is well documented in the literature that bases or,
less often, acids are used in the dihydroxylation reac-
tions for the hydrolysis of osmate esters. Additives
such as Et4NOH, Et4NOAc, Et4NF, C6H5PO3(Et4N)2,
(Et4N)2CO3, HCl, HI and tetraethylammonium salts of
chelating diacids such as o-phthalic, camphoric and
cis-1,2-cyclohexanedicarboxylic acids were effectively
used to accelerate the hydrolysis of osmium monoglyco-
late ester and thus prevent the formation of the bisglyco-
late ester (second cycle) to achieve higher ee.[26] Intro-
5
87
58c
1R,2R
[a]
Determined by HPLC analysis.
[b]
The absolute configuration was determined by comparison
of the specific rotation with the literature value.
2 equivalents of TEAA were added.
[c]
anchored to nano-MgO in their monomeric form upon duction of additives and/or slow addition of olefin to
counterionic stabilization and use.
the reaction mixture to allow the hydrolysis of the
formed osmium monoglycolate were also resorted to
to obtain higher ee. We conducted experiments to study
the influence of the heterogeneous catalyst and Et3N·
HI additive on the ee (Table 3).
Asymmetric Dihydroxylation of Olefins
Earlier, NAP-Mg-OsO4 was found to be an excellent
In the AD of methyl cinnamate under homogeneous
catalyst in the achiral dihydroxylation of olefins. In the conditions using the NMO as oxidant in H2O-t-BuOH,
present studies, we performed AD of trans-stilbene by 88% ee was obtained without slow addition of olefin.
using NAP-Mg-OsO4. A mixture of NAP-Mg-OsO4, In the AD of methyl cinnamate catalyzed by NAP-
NMO, 1 mol % of 1,4-bis(9-o-dihydroquinidinyl)phthal- Mg-OsO4 using NMO as the oxidant with slow addition,
azine [(DHQD)2PHAL] ligand was charged into a we obtained 94% ee and in the presence of Et3N·HI as
round-bottomed flask containing t-BuOH-H2O (5:1, an additive in t-BuOH-H2O, 95% ee was obtained. The
6 mL). trans-Stilbene was added to the reaction mixture Et3N·HI salt can accelerate the hydrolysis of the osmi-
slowly over a period of 12 h and continued stirring for um monoglycolate complex to subdue the second cycle
another 3 h at room temperature afforded the corre- as was done by tetraethylammonium acetate, which is
sponding chiral diol in 85% yield with 99% ee.
known for faster rates and higher ee.[27] The higher ee
NAP-Mg-OsO4 was further subjected to AD of vari- achieved in this case is attributed to Et3N·HI, which is
ous olefins and the results are summarized in Table 2. responsible for the acceleration of the hydrolysis of
Slow addition of olefin to the reaction mixture is war- the osmium monoglycolate ester.
ranted to keep the availability of the olefin at a bare min-
Thus, these results unambiguously demonstrate that
imum level in order to achieve higher ees. Olefins rang- in the present system composed of a new variant,
ing from mono- to trisubstituted, activated to simple, Et3N·HX facilitates the hydrolysis of osmium monogly-
were subjected to the dihydroxylation. In most cases, colate ester to subdue the formation of bisglycolate ester
the desired diols were formed in higher yields, albeit to achieve higher ee.
with reduced ees, when compared with results obtained
in the homogeneous system.
The scope oftheNAP-Mg-OsO4 catalyst wasextended One-Pot Synthesis of Chiral Diols
successfully to the hydroxylation of relatively larger sub-
strates such as stilbene (Table 2, entry 1) and methyl cin- Palladium-Osmium Catalytic System
namate (Table 2, entry 4). It is interesting to note that 1)
the microencapsulated catalyst developed by Kobayashi In order to generate the prochiral olefins in situ for the
was never reported for the AD of the above substrates AD reaction, NAP-Mg-PdOs was first tested in a tan-
with NMO cooxidant and 2) these chiral diol derivatives dem Heck-AD reaction, which involved stirring of iodo-
are important intermediates to several chiral ligands and benzene, styrene and Et3N at 708C in acetonitrile as sol-
drugs such as taxol, diltiazem, propranolol, etc.
vent for 12 h in the presence of 3 mol % of catalyst to
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Table 5. Solvent effects in the AD of trans-stilbene using het-
erogeneous bifunctional NAP-Mg-PdOs catalyst.[a]
Entry
Solvent
Yield [%]
ee [%]
1
2
3
4
H2O-acetone
H2O-CH3CN-acetone
H2O-CH3CN
90
85
64
80
81
80
58
85
H2O-t-BuOH
Scheme 2. Tandem Heck-asymmetric dihydroxylation cata-
lyzed by the NAP-Mg-PdOs bifunctional catalyst.
[a]
To the formed trans-stilbene product in the Heck reaction,
(DHQD)2PHAL (1 mol %) and NMO (1.3 equivs.) were
added in the solvent (6 mL).
Table 4. Tandem Heck-AD of olefins catalyzed by heteroge-
neous bifunctional NAP-Mg-PdOs catalyst.[a]
ble 5). H2O-acetone and H2O-CH3CN-acetone proved
to be good solvents for obtaining high yields. However,
H2O-t-BuOH was found to be the best solvent to obtain
high enantioselectivities similar to that obtained in the
case of homogenous catalysis[27] and the order was found
to be: H2O-CH3CN<H2O-CH3CN-acetone<H2O-
acetone<H2O-t-BuOH.
Osmium-Tungsten Catalytic System
Encouraged with the resultsobtained in the AD by using
monofunctional NAP-Mg-OsO4, we employed the het-
erogeneous bifunctional catalyst, NAP-Mg-OsW for
[a]
Mg-PdOs (3 mol %), aryl halide (1 mmol), olefin
(1 mmol) and Et3N (1.3 mmol) in CH3CN (2 mL) were
stirred at 708C for 12–16 h. After completion of the
Heck coupling, the heating was stopped and NMO
(1.3 mmol) and (DHQD)2 PHAL (7.8 mg, 0.01 mmo ) in
t-BuOH-H2O (5: 1, 6 mL) were added under stirring.
[b]
Scheme 3. Asymmetric dihydroxylation of trans-stilbene us-
ing NAP-Mg-OsW.
ee was determined by HPLC analysis.
Table 6. Synthesis of chiral diols by heterogeneous bifunc-
tional NAP-Mg-OsW catalyst using H2O2 as the terminal oxi-
give trans-stilbene. After completion of the reaction, as
monitored by TLC, the heating was stopped and a mix- dant.[a]
ture of (DHQD)2PHAL (1 mol %) and NMO in t-
BuOH-H2O (5:1, 6 mL) was introduced and stirred at
room temperature for 12 h to obtain the desired diol in
80% yield with 85% ee (Scheme 2). The methodology
described here uses bulk chemicals such as styrene and
acrylates as starting materials to prepare the prochiral
substrates, stilbenes and cinnamates, in situ and upon di-
hydroxylation gives chiral diols in a single-pot process.
The results are outlined in Table 4. This catalyst exhibits
good performance for a number of cycles with NMO as
cooxidant. After completion of the reaction the catalyst
[a]
was recovered by simple filtration.
The olefin (1 mmol), NAP-Mg-OsW (3 mol %),
We examined the effect of the solvent on the activity
and enantioselectivity in the NAP-Mg-PdOs-catalyzed
AD of trans-stilbene using NMO as the cooxidant (Ta-
(DHQD)2PHAL (1 mol %) and NMM (50 mol %) were
taken in the solvent (6 mL) and H2O2 was slowly added
over 12 h under stirring.
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Table 7. Solvent effects in the AD-N-oxidation of trans-stil-
bene catalyzed by NAP-Mg-OsW catalyst.[a]
Entry
Solvent
Yield [%]
ee [%]
1
2
3
4
H2O-acetone
H2O-CH3CN-acetone
H2O-CH3CN
82
80
60
70
75
70
55
80
H2O-t-BuOH
[a]
The olefin (1 mmol), NAP-Mg-OsW (3 mol %),
(DHQD)2PHAL (1 mol %) and NMM (50 mol %) were
taken in the solvent (6 mL) and H2O2 was slowly added
over 12 h under stirring.
the simultaneous AD of trans-stilbene and N-oxidation
of NMM in the presence of H2O2, used as terminal oxi-
dant, and (DHQD)2PHAL as ligand. To a mixture of
3 mol % of NAP-Mg-OsW, 3 mol % of (DHQD)2
PHAL ligand, trans-stilbene and NMM in t-BuOH-H2
O (5:1, 6 mL ), H2O2 was slowly added over a period
Scheme 5. A schematic representation of NAP-Mg-PdOs-
and NAP-Mg-OsW-catalyzed synthesis of chiral diols.
of 12 h to afford the desired diol (Scheme 3). Various problem of catalyst recovery, while the basic advantage
olefins, mono- and disubstituted, activated and simple, of our process is the recyclability of the catalysts which
were subjected to AD and the results are presented in will be established in a later section.
Table 6.
We have obtained higher ees with the monofunctional
We also examined the effect of the solvent on the ac- osmium catalyst than with the bifunctional catalysts.
tivity and enantioselectivity in the NAP-Mg-OsW-cata- The slow addition of olefins is an effective factor with
lyzed AD of trans-stilbene using H2O2 as the terminal the monofunctional catalysis.
oxidant (Table 7). The HO-acetone system proved to
A plausible mechanism for the triple catalytic H2O2
2
be a good solvent for obtaining high yields. However, oxidation with osmium-tungsten oxides is depicted in
t-BuOH-H2O was found to be the best solvent to obtain Scheme 4. The peroxo species generated from tungstate
high enantioselectivities similar to that obtained in the and H2O2 rapidly recycles the NMM to NMO, which in
case of homogenous catalysis[27] and the order was found turn reoxidizes OsVI to OsVIII
.
to be: H2O-CH3CN<H2O-CH3CN-acetone<H2O-
acetone<H2O-t-BuOH.
In summary, the bifunctional catalysts, NAP-Mg-
PdOs and NAP-Mg-OsW, were subjected to tandem
The novel protocol used here afforded diols using Heck-AD and AD-N-oxidation reactions in a single-
NMM in catalytic amounts and a cheaper oxidant, H2 pot separately as described in Scheme 5 to obtain chiral
O2, by a heterogeneous catalyst instead of NMO in stoi- diols.
chiometric amounts currently used in dihydroxylations.
This methodology offers the diols with higher yields and
moderate ees. This process rivals that employed by Reusability and Heterogeneity
Bäckvall et al. using flavin, a biomolecule, induced cat-
alytic oxidation of NMM to NMO in the dihydroxyla- These catalysts were recovered quantitatively by sim-
tion.[28] The flavin-based process suffers from the serious ple filtration. The recovered catalysts were reused
Scheme 4. Os- and W-catalyzed synthesis of diols using H2O2 as the terminal oxidant.
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Conclusion
In summary, a single-pot biomimic synthesis of chiral di-
ols mediated by bifunctional solid catalysts consisting of
active palladium, osmium and tungsten species embed-
ded on a matrix of the nano-MgO, representing a low-
cost process, is described. Here the desired prochiral
olefins and N-methylmorpholine N-oxide, key inter-
mediates for AD, are generated in situ in the most eco-
nomical way by Heck coupling and N-oxidation of N-
methylmorpholine, respectively. Dispensing with the
usual protocol of isolation and purification of the inter-
Figure 3. Enantioselectivities obtained in multiple uses of mediates, the bifunctional catalysts trigger the reaction,
NAP-MgOsO4 , NAP-Mg-PdOs, NAP-Mg OsW in the AD
of trans-stilbene.
to obtain the chiral diols with minimum waste and max-
imum conservation of energy. The oxidant, H2O2, em-
ployed here in place of NMO is environmentally accept-
able, as the only byproduct is water. More interestingly,
even the water produced from H2O2 during the N-oxida-
and consistent activity and enantioselectivity were no- tion is consumed in the AD reaction to mark the highest
ticed even after the fifth cycle (Figure 3). When the atom economy in theproduction of chiral diols. This pro-
fresh reaction was conducted with the filtrate obtained tocol provides the desired prochiral olefins in situ en
at the end of the dihydroxylation reaction, no product route to chiral diols from cheaper precursors and
formation was observed. Moreover, the absence of os- NMO via in situ oxidation to minimize the unit opera-
mium as determined by iodometry, SEM-EDAX and tions. The possible large-scale synthesis of diols employ-
no progress of the dihydroxylation reaction with the fil- ing this catalytic system using H2O2 as the oxidant direct-
trate samples withdrawn periodically during reaction ed to minimize the solid waste effluent is addressed. In
and filtered rule out the leaching of osmium and unam- contrast to the homogeneous catalysts, the heterogene-
biguously provide evidence for heterogeneity through- ous bifunctional catalysts were easily recovered from
out the reaction (see Experimental Section for further the reaction by simple filtration and reused successfully
details).
in the AD. The recyclable catalysts and the use of cheap-
It is interesting to note that the NAP-AP-MgO er oxidant, H2O2, employed here make the process more
holds both the OsO42À and the Os(VIII) species possi- economical thanthe earlier processes. The simpleproce-
bly through electrostatic interactions. The other possi- dure, easy recovery and reusable catalytic systems are
bility could be that the reduction of Os(VIII) to expected to contribute to the development of benign
Os(VI) is too fast to detach neutral OsO4 from the chemical processes and products.
support. However, when NAP-Mg-OsO4 is treated
with the oxidant in the absence of olefin, osmium is
found to leach from the support, which indicates that
the NAP-Mg-OsO4 catalyst is not stable in the oxida-
Experimental Section
tive environment.
The bifunctional catalysts comprising of Pd, Os, W
performed Heck coupling, N-oxidation and AD reac-
tions, exhibiting their characteristic features in the diver-
sified bifunctional activities without loosing their identi-
ty. These results substantiate the retention of coordina-
tion geometries of metal complexes in their monomeric
General Remarks
IR spectra for samples as KBr pellets were recorded on a BIO-
RAD 175C FTIR spectrometer. 1H NMR spectra were record-
ed on a Varian Gemini 200 MHz spectrometer. Chemical shifts
(d) are reported in ppm, using TMS as internal standard. X-ray
powder diffraction (XRD) data were collected on a Siemens/
form as supported by IR spectral data and rule out the D-5000 diffractometer using Cu-Ka radiation (l¼1.5405 ꢁ).
SEM-EDAX (scanning electron microscopy-energy dispersive
X-ray analysis) was performed on a Hitachi SEM S-520, EDX-
Oxford Link ISIS-300 instrument. High performance liquid
chromatography (HPLC) was performed using the following
apparatus: Shimadzu LC-10AT(liquid chromatograph), Shi-
madzu SPD-10A (UV detector) and Shimadzu C-R6A Chro-
matopac. ACME silica gel (100–200 mesh) was used for col-
umn chromatography and thin layer chromatography was per-
formed on Merck precoated silica gel 60-F254 plates. X-ray pho-
toemission spectra were recorded on a Kratos AXIS 165 with a
dual anode (Mg and Al) apparatus using the MgKa anode. The
formation of biheterometallic species during the stabili-
zation process and the dihydroxylation reaction. The
large positive electric potential of the exchanged cata-
lyst surface induces an enrichment of cooxidant close
to the surface. Similarly, the olefin and the aryl halide
also build up their concentrations close to the surface
as it has a high adsorption coefficient on the support sur-
face. Apart from this, spatial organization and electrical
shielding[29] are responsible for the excellent perform-
ance of the exchanged catalysts.
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Boyapati M. Choudary et al.
FULL PAPERS
pressure in the spectrometer was about 10À9 Torr. For energy
calibration, we have used the carbon 1 s photoelectron line.
The carbon 1 s binding energy was taken to be 285.0 eV. Spec-
tra were deconvoluted using Sun Solaris based Vision 2 curve
resolver. The location and the full width at half maximum
(FWHM) for a species were first determined using the spec-
trum of a pure sample. The location and FWHM of products,
which were not obtained as pure species, were adjusted until
the best fit was obtained. Symmetrical Gaussian shapes were
used in all cases. Binding energies for identical samples were,
in general, reproducible to within ꢀ0.1 eV.
General Procedure for Synthesis of Chiral Diols via
Tandem Heck-Asymmetric Dihydroxylation using
NAP-Mg-PdOs Bifunctional Catalyst
The heterogeneous bifunctional catalyst NAP-Mg-PdOs
(80 mg, 3 mol %), aryl halide (1 mmol), olefin (1 mmol) and
Et3N (111 mg 1.1 mmol) were taken in acetonitrile solvent
and stirred at 708C for 12–16 h. At this stage, the heating
was stopped and a mixture of (DHQD)2PHAL (7.8 mg,
1 mol %), NMO (175 mg, 1.3 mmol) and H2O-t-BuOH (1:5,
6 mL) was added to the above reaction mixture and stirred at
room temperature. After completing the reaction (TLC analy-
sis), Na2SO3 (0.8 g) and ethyl acetate were added to the reac-
tion mixture and the catalyst was filtered off and washed
with ethyl acetate (10 mL). The combined filtrates were ex-
tracted with 1 N HCl (2ꢁ5 mL) to recover the chiral ligand
from the aqueous layer. The resulting organic phase was fur-
ther washed with brine solution (5 mL) and the solvent was re-
moved. The thus obtained crude material was chromatograph-
ed on silica gel using hexane/ethyl acetate (2:1) as an eluent to
afford the corresponding cis-diol.
K2OsO4 ·2 H2O, TEAA, (DHQD)2PHAL and NMO were
purchased from Aldrich. Haloarenes and olefins were pur-
chased from Aldrich. All the other solvents and chemicals
were obtained from commercial sources and used as such with-
out further purification.
Preparation of the NAP-MgO-Supported Catalysts
NAP-Mg-OsO4: NAP-MgO (SA 600 m2/g, 1 g) was treated
with K2OsO4 (0.184 g, 0.5 mmol) dissolved in decarbonated
water with stirring for 12 h under a nitrogen atmosphere to af-
ford NAP-Mg-OsO4. Then the catalyst was filtered off and
washed with deionized water, acetone, and dried.
NAP-Mg-PdOs: Na2PdCl4 and K2OsO4 (0.147 g and 0.184 g,
each 0.5 mmol) were dissolved in decarbonated water. NAP-
MgO (SA 600 m2/g, 1 g) was added to the mixture and stirred
for 12 h under a nitrogen atmosphere to afford NAP-Mg-
PdOs. Then the catalyst was filtered and washed with deionized
water, acetone, and dried to obtain 1.235 g of Mg-PdOs
(0.375 mmol gÀ1 each of Pd and Os).
NAP-Mg-OsW: K2OsO4 and Na2WO4 (0.184 g and 0.165 g
each 0.5 mmol) were dissolved in decarbonated water and
then NAP-MgO (SA 600 m2/g, 1 g) was added to the mixture
and stirred for 12 h under a nitrogen atmosphere to afford
NAP-Mg-OsW. Then the catalyst was filtered and washed
with deionized water, acetone, and dried to obtain 1.345 g of
Mg-OsW (0.370 mmol gÀ1 each of Os and W).
Asymmetric Dihydroxylation of Olefins using NAP-
Mg-OsW and H2O2 as the Terminal Oxidant
The heterogeneous bifunctional NAP-Mg-OsW (81 mg,
3 mol %), an olefin (1 mmol), (DHQD)2PHAL (7.8 mg,
1 mol %) and NMM ( 50.5 mg, 0.5 mmol) were taken in a
round-bottomed flask containing H2O-t-BuOH (1:5, 6 mL).
To this mixture was added H2O2 (169 mL, 30% aqueous,
1.5 mmol) over a period of 12 h. After completion of the reac-
tion as indicated by TLC analysis, Na2SO3 (0.8 g) and ethyl ace-
tate were added to the reaction mixture, and stirred for 10 mi-
nutes. The catalyst was then filtered off and washed with ethyl
acetate (10 mL). The combined filtrates were extracted with 1
N HCl (2ꢁ5 mL) to recover the chiral ligand from the aqueous
layer. The resulting organic phase was further washed with
brine solution (5 mL) and the solvent was removed. The thus
obtained crude material was chromatographed on silica gel us-
ing hexane/ethyl acetate (2:1) as an eluent to afford the corre-
sponding cis-diol.
Heterogeneity Tests
Synthesis of Chiral Diols with NAP-Mg-OsO4 using
NMO as the Cooxidant
We evaluated the heterogeneity of the catalysts in all respects.
To understand the stability and heterogeneity of the mono- and
bifunctional catalysts, we conducted a series of experiments to
obtain clear evidence for the heterogeneity of the reaction.
Experiment 1: A mixture of the Mg-OsO4, a-methylstyrene
and NMO in H2O-CH3CN-acetone was stirred for 8 h. After
completion of the reaction, the catalyst was separated by filtra-
tion. To one part of the filtrate were added fresha-methylstyr-
ene, NMO and the mixture was stirred for 24 h. There was no
enhancement of the product in the reaction using the fresh a-
methylstyrene. To the second part of the solution were added
a different olefin, trans-stilbene, NMO and the mixture was
stirred for 24 h. No stilbene diol was formed.
NAP-Mg-OsO4 (71 mg, 3 mol %), NMO (175 mg, 1.3 mmol),
(DHQD)2PHAL ( 7.8 mg, 1 mol %) were taken in a round-bot-
tomed flask containing H2O-t-BuOH (1:5, 6 mL). To the reac-
tion mixture, 1 mmol of olefin was added slowly over a period
of 12 h and the reaction was continued for 3 h at room temper-
ature. After completion of the reaction (TLC analysis), Na2SO3
(0.8 g) and ethyl acetate were added to the reaction mixture,
which was stirred for 10 minutes, then the catalyst was filtered
off and washed with ethyl acetate (10 mL). The combined fil-
trates were extracted with 1 N HCl (2ꢁ5 mL) to recover the
chiral ligand from the aqueous layer. The resulting organic
phase was further washed with brine solution (5 mL) and the
solvent was removed. After removing the solvent, the crude
material was chromatographed on silica gel using hexane/ethyl
acetate (2:1) as an eluent to afford the corresponding cis-diol.
Experiment 2: A mixture of the Mg-OsO4, a-methylstyrene
and NMO in H2O-CH3CN-acetone and was stirred. At differ-
ent intervals (for every 2 h) the samples were withdrawn and
filtered (four times). To these filtrates were added a different
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Bifunctional Catalysts Stabilized on Nanocrystalline Magnesium Oxide
FULL PAPERS
olefin, trans-stilbene, NMO and the mixture was stirred for
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was detected in those filtrates by the SEM-EDX. These results
strongly suggest that the OsO4 is bound to the support during
the reaction when all the constituents are present. It appears
that during oxidation with NMO the anionic form of OsO4
transforms into an Os(VIII) species, but is bound on MgO
through some other electrostatic interaction that includes hy-
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was leached during the reaction.
Experiment 3: A mixture of Mg-OsO4 and NMO in H2O-
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and NMO were added and stirred at room temperature for 8 h.
The diol was obtained in good yield.
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K. Jyothi thanks the Council of Scientific and Industrial Re-
search (CSIR) India, and Moumita Roy thanks University
Grants Commission (UGC), New Delhi for the award of a re-
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