Silica Gel-Supported Cinchona Alkaloid-OsO4 Complex for Catalytic Heterogeneous Asymmetric Dihydroxylation of Olefins by H2O2 using a Titanium Silicalite-Based Coupled Catalytic System

Article abstract of DOI:10.1002/1615-4169(200207)344:5<503::AID-ADSC503>3.0.CO;2-9

A triple catalytic system designed for asymmetric dihydroxylation of olefins, composed of NMM and two divergent heterogeneous catalysts, titanium silicalite and silica gel-supported 1,4-bis(9-O-dihydroquinidinyl)phthalazine [SGS-(DHQD)₂ PHAL)]-OsO₄ complex relays the transport of two electrons from olefin to H₂O₂ used as a terminal oxidant to provide chiral diols with good yields and high enantiomeric excesses in a single pot.

Full text of DOI:10.1002/1615-4169(200207)344:5<503::AID-ADSC503>3.0.CO;2-9

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Silica Gel-Supported Cinchona Alkaloid-OsO4 Complex for
Catalytic Heterogeneous Asymmetric Dihydroxylation of Olefins
by H2O2 using a Titanium Silicalite-Based Coupled Catalytic
System
Boyapati M. Choudary,* Naidu S. Chowdari, Karangula Jyothi, Sateesh Madhi,
Mannepalli L. Kantam
Inorganic and Physical Chemistry Divisions, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: ( ‡ 91) 40-7160921, e-mail: choudary@iict.ap.nic.in
Received: March 11, 2002; Accepted: April 29, 2002
amounts and the cumbersome procedures practiced
Abstract: A triple catalytic system designed for
for the recovery of the by-product, N-methylmorphline
asymmetric dihydroxylation of olefins, composed of
and its reoxidation to NMO in separate units accrue
NMM and two divergent heterogeneous catalysts,
additional costs to the process. The biomimetic ap-
titanium silicalite and silica gel-supported 1,4-bis(9-
proach to realize multi-step reactions, composed of
O-dihydroquinidinyl)phthalazine [SGS-(DHQD)2
multi-component systems in a single-pot synthesis, is an
PHAL)]-OsO4 complex relays the transport of two
attractive strategy to achieve the ideal organic synthesis
electrons from olefin to H2O2 used as a terminal
in terms of conservation of energy, abatement of
oxidant to provide chiral diols with good yields and
pollutants, lowering the inventory of equipment and
high enantiomeric excesses in a single pot.
processing time.[9] An interesting development was
made by Backvall et al. in realizing a more highly
economical process by using H2O2, the terminal oxidant,
in molar equivalents and NMM in catalytic amounts to
Keywords: asymmetric synthesis; diols; immobiliza-
tion; olefins; osmium; oxidation
continuously generate NMO in situ via oxidation of the
latter using biomimetic flavin as the electron transfer
mediator in the multi-component catalytic system for
[10]
Osmium-catalyzed asymmetric dihydroxylation (AD) ADreactions of olefins.
However, the flavin is
of olefins provides one of the most elegant methods for unstable and cannot be reused in the dihydroxylation
the preparation of chiral vicinal diols, the key inter- process. Recently, we demonstrated the reoxidation of
mediates for many biologically active compounds.[1] He- NMM to facilitate continuous in situ production of
terogenization of the chiral ligands on various polymers[2] NMO to sustain the Os(VI)/Os(VIII) catalytic cycle
and silica gel[3] is undertaken in order to effect the easy induced by a reusable bifunctional heterogeneous
recovery of the expensive ligands and to some extent catalyst composed of osmium and tungsten oxides on a
OsO4 after the reaction for reuse. Recently, osmium is single matrix using H2O2 as the terminal oxidant.[11] In
immobilized on various supports based on microencap- continuation of our interest on cost effective method-
sulation[4] and ion-exchange techniques[5] to achieve com- ologies, we report here a divergent approach using a
plete recovery of osmium. Various cooxidants such as N- triple catalytic system composed of NMM and two
methylmorpholine N-oxide (NMO),[6] potassium ferri- heterogeneous catalysts in which titanium silicalite (TS-
cyanide,[7] and molecular oxygen[8] are employed to re- 1) acts as electron transfer mediator (ETM) to perform
oxidize the osmium in ADreactions. However, each of
oxidation of NMM used in catalytic amounts with
these oxidants has its own disadvantages. For example, hydrogen peroxide to provide in situ NMO continuously
employing three molar equivalents of potassium ferri- for ADof olefins, which is catalyzed by another
cyanide per mole of the olefin in ADleaves a large
heterogeneous catalyst, silica gel-supported Cinchona
amount of solid waste as effluent to render the process alkaloid [SGS-(DHQD)2PHAL]-OsO4 for the first time
incompatible to the environment and possibly uneco- (Scheme 1). The triple redox catalytic system devised to
nomical for large-scale operations, while molecular perform oxidation of TS-1, NMM, and Os(VI) using
oxygen gives lower ee×s and yields. The use of NMO- molar quantities of H2O2, a cheaper terminal oxidant,
based dihydroxylations is thus rejuvenated due to the offers chiral diols in a single pot to make the process
easy adaptability for large-scale operations.[6d, e] How- more economical. Incidentally, this forms the first report
ever, the use of expensive NMO in stoichiometric of TS-1-catalyzed oxidation of tertiary amines for SGS-
Adv. Synth. Catal. 2002, 344, No. 5
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1615-4150/02/34405-503 506 $ 17.50+.50/0
503

Boyapati M. Choudary et al.
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Me
N
R2
OsO3
H2O
TiOH
R1
O
O
Me
HO
R2
N
O
TiOOH
OsO4
H2O2
R1
OH
Scheme 1. The catalytic cycle in the osmium-catalyzed dihydroxylation using H2O2 as the terminal oxidant.
Figure 1. SGS-(DHQD)2PHAL.
(DHQD)2PHAL-OsO4-catalyzed ADreaction with
H2O2.
The silica gel-anchored bis-Cinchona alkaloid was
Table 1. Asymmetric dihydroxylation of olefins using SGS-(DHQD)2PHAL-
OsO4/NMM/TS-1/H2O2.[a]
R2
R2
HO
R1
prepared by adopting the modifications to the reported
procedure.[3b] The reaction of 4-(9-O-dihydroquinidin-
yl)-1-(9-O-quinidinyl)phthalazine with mercaptoprop-
yl-silica gel in the presence of AIBN as the radical
initiator in chloroform gave SGS-(DHQD)2PHAL
(Figure 1). The elemental analysis results confirmed
the incorporation of 15.34 wt % of monomeric alkaloid
on the silica gel. The BET surfaces of silica gel and silica-
SGS-(DHQD)2PHAL-OsO4
TS-1, t-BuOH-H2O
NMM, H2O2, rt, 12h
R1
OH
ee (%)
98
olefin
entry
1
yield (%)
94
CO2Me
Ph
anchored alkaloid were found to be 249 and 152 m2 g ,
respectively. The reduction in the surface area after
anchoring is due to the presence of the chiral ligand on
the surface of silica gel.
1
CO2Et
99
91
2
MeO
Recently, titanium silicalite (TS-1) with MFI top-
ology[13] was foundtopossess very goodredox properties
in catalyzing oxidation reactions. TS-1 with H2O2
oxidant serves as a reusable catalyst and is easily
separable by simple filtration.
The in situ generated SGS-(DHQD)2PHAL-OsO4
complex, TS-1, and NMM employed in catalytic
amounts in the ADreaction of methyl cinnamate using
H2O2 as oxidant in H2O-t-BuOH afforded the corre-
sponding diol in excellent yield and ee (Table 1,
Entry 1).
99
93
75
55
Ph
Ph
3
4
5
Ph
91
89
90
72
Ph
Ph
6[b]
In an effort to widen the scope and application of the
triple catalytic system, various substrates were subjected
for ADunder similar conditions. The results are
summarized in Table 1. SGS-(DHQD)2PHAL-OsO4
exhibited equivalent activity and ee compared with that
of homogeneous analogue, (DHQD)2PHAL-OsO4.[6]
[a] All the chiral diols were well characterized by NMR, MS and IR.
The ee is measured by HPLC analysis (see ref. 5a). For entry 3
the results are without slow addition of olefin.
[b] Olefin and H2O2 were added slowly over a period of 20 h.
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Silica Gel-Supported Cinchona Alkaloid-OsO4 Complex
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Slow addition of the olefin to the reaction mixture is decreased, while the ee remained the same (Run 4).
warranted, except in the case of trans-stilbene, to keep With extended reaction time (20 h) the yield is im-
the availability of the olefin at a bare minimum level to proved. In this heterogeneous system, excellent ee has
achieve higher ee. For example, with slow addition of been achieved with an equimolar ratio of ligand to
styrene, the corresponding diol was obtained with 93% osmium, in contrast to the homogeneous reaction where
ee as against 76% ee when charged in one portion at the an excess of the expensive chiral ligand to osmium is
beginning of the reaction. These observations are in required.[1,6,10] This indicates that the binding ability of
agreement with earlier findings.[6a] In the case of the present heterogeneous osmium catalyst is greater
cinnamates we achieved excellent ee×s (Entry 1; 98% than that of the homogenous analogue.[3b]
and Entry 2; 99%) as against the reported 88% ee.[6e]
It is a highly attractive proposition to apply TS-1
The improved ee×s are attributed to the slow addition of catalyzed N-oxidation to the recycling of NMM to NMO
the olefin and oxidant. Various olefins ranging from in the SGS-(DHQD)2PHAL-OsO4-catalyzed ADreac-
mono- to trisubstituted, activated to simple were sub- tion, which provides reoxidation of Os(VI). The mech-
jected to the dihydroxylation. In most cases, the desired anism ofthe triple catalytic H2O2 oxidation is depicted in
diols were formed in higher yields and ee×s similar to Scheme 1. The oxidation involves a transport of two
those obtained under homogeneous catalysis. The electrons from the olefin to hydrogen peroxide medi-
trisubstituted olefin was also dihydroxylated to the ated by a cascade of electron transfer reactions. The
corresponding diol with higher ee in the presence of Os(VIII) directly dihydroxylates the olefin and the
tetraethylammonium acetate (TEAA) additive and an Os(VI) formed is efficiently reoxidized by NMO. The
increase of the addition time for olefin and H2O2 from 12 recycling of NMM to NMO is, in turn, effected by the
to 20 h (Entry 6). This phenomenon substantiates that titanium hydroperoxo species and the TS-1 is reoxidized
the hydrolysis of osmate ester, a pronounced slow by H2O2. The highly controlled kinetic reactions effect
process in the case of trisubstituted olefins, was accel- the dihydroxylation selectively. For example, the olefin
erated with the addition of the additive to afford higher is coordinated to Os(VIII), the N-oxide to Os(VI),
ee.[6a] Thus, higher ee×s in the ADreaction are possible
NMM to titanium hydroperoxo species and finally
using H2O2 as oxidant catalyzed by SGS-(DHQD)2 hydrogen peroxide to TS-1 to relay the transport of
PHAL-OsO4. H2O2 serves as a better oxidant if slow electrons effectively and selectively. It is very remark-
addition of the oxidant and olefin is administered to able that the triple catalytic system composed of two
minimize the secondary cycle, which is considered to divergent heterogeneous systems helps to relay the
lower the ee. H2O2 is believed to be the most economical transport of electrons through interaction with H2O2,
and environmentally acceptable oxidant in industry, NMM, NMO and olefin very effectively to open a new
since the only by-product is water.
The recovered SGS-(DHQD)2PHAL-OsO4/TS-1 was
era in the catalysis
In summary, the SGS-(DHQD)2PHAL-OsO4/NMM/
reused successfully in AD, albeit after replenishment of TS-1/H2O2 system has been successfully employed for
~30% osmium source in the form of K2OsO4 ¥ 2 H2O heterogeneous ADof olefins to afford the chiral diols
which was leached during the reaction (Table 2). When with higher yields and ee×s. Coupling of the ADreaction
the catalyst was reused as such without further addition with the in situ N-oxidation in a single pot indeed
of osmium in the ADreaction, the activity was
reduces the unit operation, energy and the amount of
NMM used in place of NMO by 50%. The possible large-
scale synthesis of diols employing the heterogeneous
catalyst H2O2 as an oxidant directed to minimize the
solid waste effluent is also addressed. The use of the
cheaper H2O2-NMM system in place of the relatively
expensive NMO is a better option to offer a cost-
effective process. The simple procedure, easy recovery
and reusable catalytic systems are expected to contrib-
ute to the development of benign chemical processes
and products.
Table 2. Reuse of catalyst in the AD of methyl cinnamate.[a]
Run
Time [h]
Yield [%]
ee [%]
98
94
91
12
12
1
2
98
96
97
92
12
12
3
69 (90)[c]
Experimental Section
4[b]
[a] Runs 2 and 3 were carried out using recovered catalyst
with addtion of 0.3 mol % K2OsO4 · 2 H2O.
[b] Reaction was carried out using the recovered catalyst
from run 3.
Preparation of SGS-(DHQD)2PHAL
Silica gel (200 mesh; 4 g) was treated with 18 mL of 3-
mercaptopropyltrimethoxysilane in 22 mL of anhydrous 1:1
pyridine/toluene. The slurry was heated at 90 8C for 24 h. After
[c] Yield obtained after 20 h.
Adv. Synth. Catal. 2002, 344, 503 506
505

Boyapati M. Choudary et al.
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filtration, the solid was washed with toluene followed by
Soxhlet extraction with toluene, then dried under vacuum for
1 h to give 3-mercaptopropyl-silica gel containing 3.38% S,
corresponding to 1.05 mmol of S per gram.
This derivatized silica gel (2 g) was suspended in chloroform
and refluxed with 4-(9-O-dihydroquinidinyl)-1-(9-O-quinidi-
nyl)phthalazine (0.781 g, 1 mmol) and AIBN (55 mg) as
radical initiator for 48 h. The solid was filtered followed by
washing with methanol, Soxhlet extraction with toluene and
drying under vacuum for 1 h to give SGS-(DHQD)2PHAL
(1.66 wt % of N, corresponding to 0.197 mmol of alkaloid per
gram).
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Typical Procedure for Asymmetric Dihydroxylation of
Olefins using SGS-(DHQD)2PHAL-OsO4/NMM/TS-1
with H2O2
SGS-(DHQD)2PHAL (50 mg, 0.01 mmol), K2OsO4 ¥ 2 H2O
(3.68 mg, 0.01 mmol), NMM (50 mg, 0.5 mmol), TEAA
(522 mg, 2 mmol), TS-1 (20 mg, 0.038 mmol of Ti/g, Si/Ti: 32)
in t-BuOH-H2O (3:1, 5 mL) were stirred at room temperature
for 20 min. To this mixture were added an olefin (1 mmol) and
H2O2 (169 mL, 30% aqueous, 1.5 mmol) over a period of 12 h
using separate syringe pumps. After the addition was complete,
the reaction mixture was stirred for another 1 h and the catalyst
was filtered and washed with ethyl acetate. The solvent was
removed and the crude material was chromatographed on
silica gel to afford the corresponding cis-diol.
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Acknowledgements
N. S. C. and S. M. thank the Council of Scientific and Industrial
Research, India, for the award of senior research fellowship.
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