Silica-supported tantalum catalysts for asymmetric epoxidations of allyl alcohols

Article abstract of DOI:10.1002/(SICI)1521-3773(19991203)38:23<3540::AID-ANIE3540>3.0.CO;2-U

Tantalum good, titanium bad: This appears to be the case for silica- supported catalysts for the asymmetric epoxidation of allyl alcohols. Complexes such as [SiO-Ta(OEt)₄] were prepared from silica and [Ta(=CHCMe₃)(CH₂CMe₃)₃], and in the presence of a tartrate and an alkyl hydroperoxide, these surface tantalum compounds lead to efficient and convenient catalysts for the asymmetric epoxidation of 2-propen-1-ol (R = H) and trans-2-hexen-1-ol (R = nPr; see reaction).

Full text of DOI:10.1002/(SICI)1521-3773(19991203)38:23<3540::AID-ANIE3540>3.0.CO;2-U

COMMUNICATIONS
OEt
Ta
Silica-Supported Tantalum Catalysts for
EtO
OEt
Asymmetric Epoxidations of Allyl Alcohols
O
Ta
OEt
O
Si
Damien Meunier, Arnaud Piechaczyk,
Aimery de Mallmann,* and Jean-Marie Basset*
3a
Si
EtOH
NpH
OH
Si
2a
Ta
+
+
+
NpH
OEt
EtO
Ta
O
silica(500)
1
Asymmetric epoxidation of allyl alcohols is an important
reaction in synthetic organic chemistry.[1, 2] Katsuki and
Sharpless[3] have provided a successful solution which is now
used for industrial applications.[4] Although this catalytic
process seems to be well understood,[5±8] a heterogeneous
system would be advantageous.[9] It could avoid a complicated
separation of product from catalyst, which can lead to
decomposition of the epoxide formed.[6±8]
Ta
O
OEt
O
O
Si
Si
Si
Si
2b
3b
Scheme 2. Preparation of silica-supported tantalum alkoxides. NpH ˆ
Neopentane.
Several oxide-supported titanium compounds were pre-
pared for catalytic epoxidations of allyl alcohols.[10±13] How-
ever, the enantioselectivity was not reported, the metal may
leach from the support, or the preparation of the solids seems
to be difficult to reproduce.[9] The choice of titanium to graft a
Sharpless-type catalyst is perhaps not the right one, since the
mechanism usually accepted requires a coordination sphere in
which the four d electrons of Ti are involved in s bonds with a
tartrate group chelating the metal through two s-bonded
oxygen atoms, an allyl alkoxy group, and a s/p-coordinated
tert-butyl peroxo group (Scheme 1).[5] If Tiiv is grafted through
one Si-O-Ti bond, then it cannot accomodate all these ligands.
However, a Group 5 metal should be a potential active site.
of exchanging the alkyl and akylidene ligands of 2a and 2b
with ethanol in order to obtain surface alkoxy ± tantalum
complexes 3a and 3b.[16] We refer to the solids prepared in this
way as [Ta]#1 ± [Ta]#3.[17] A titanium catalyst, [Ti], was
similarly prepared from silica(500) and Ti(OiPr)4 (1.8 wt% Ti).
These tantalum- and titanium-containing solids were then
used as catalysts for the asymmetric epoxidation of 2-propen-
1-ol and trans-2-hexen-1-ol. The results, obtained after 48 h of
reaction, are presented in Table 1. As already observed by
Sharpless,[7] when associated to (‡)-diisopropyl tartrate ((‡)-
DIPT), Ti(OiPr)4 leads to an active and enantioselective
catalyst for epoxidation of 2-propen-1-ol into (S)-glycidol
(Table 1, entry 1; turnover number (TON) ˆ 15 mol of glyci-
dol produced per mol of titanium, 80% ee). The grafted
titanium species in [Ti] leads to a poorly active catalyst and
exhibits nearly no enantioselectivity (entry 2). Molecular
Ta(OEt)5 does not lead to an active catalyst (entry 3), and
the opposite enantiomer, (R)-glycidol, is obtained predom-
inantly. Interestingly, upon use of the silica-supported tanta-
lum species [Ta]#1 ± [Ta]#3, good activity and enantioselec-
tivity are observed with molecular sieves (entry 4; TON ˆ
28 mol of glycidol produced per mol of surface tantalum,
85% ee) or without molecular sieves (entry 5; TON ˆ 15,
84% ee); the major enantiomer is (S)-glycidol. As expected,
with the opposite tartrate, ( )-DIPT, the same results are
obtained, but (R)-glycidol is the major product (compare
entries 5 and 6).
OR
O
OR
O
O
O
C
C
O
O
O
O
Ti
O
Ta CO2R
O
CO2R
O
O
O
Si
tBu
tBu
Scheme 1. Left: Coordination sphere of titanium proposed by Sharpless
et al.[5] for the active sites in asymmetric epoxidations of allyl alcohols (only
half of a dimer is shown). Right: Hypothetical coordination sphere of
tantalum for a potential silica-supported active site.
Tantalum, which exhibits a low activity in homogeneous
catalysis,[1] could thus be a good candidate for such hetero-
geneous catalysis. We report here results which demonstrate
that silica-supported tantalum species lead to active catalysts
for these asymmetric epoxidations.
The results show that the activity of silica-supported
tantalum is due to surface sites and not to dissolved species
since 1) molecular Ta(OEt)5 leads to almost inactive species
with the major formation of the opposite enantiomer; 2) the
chemical analysis (Ta or Ti) of the final solution and of the
solids before and after reaction does not indicate any metal
leaching (less than 2% of the supported metal); and 3) when
the solid catalyst was isolated by filtration before the
introduction of the last reactant, tert-butyl hydroperoxide
(TBHP) or 2-propen-1-ol, as recommended by Sheldon
et al.,[18] the solutions were found to be inactive.
Silica-supported tantalum ethoxides were prepared in two
steps (Scheme 2). The first step consists of grafting
[14]
ˆ
Ta( CHCMe3)(CH2CMe3)3 (1) onto silica(500)
.
Two surface
tantalum species are then obtained: 2a (ca. 50%), which is
grafted to silica by one Si-O-Ta bond, and 2b (ca. 50%),
which is grafted by two such bonds.[15] The second step consists
A precise comparison of the turnover frequencies (TOF)
obtained for the molecular Ti catalyst and for the supported
Ta species is not possible since we do not have enough kinetic
data. Furthermore, we were not able to synthesize glycidol
under experimental conditions similar to usual Sharpless
conditions (0.5m alcohol with a metal/substrate ratio of 5/
100).[7] It is difficult to work with concentrations higher than
[*] Dr. A. de Mallmann, Dr. J.-M. Basset, D. Meunier, A. Piechaczyk
Â
Laboratoire de Chimie Organometallique de Surface, CPE-Lyon
43, Boulevard du 11 Novembre 1918
F-69616 Villeurbanne Cedex (France)
Fax: (‡33)4-72-43-17-95
E-mail: basset@coms1.cpe.fr
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COMMUNICATIONS
Table 1. Catalytic asymmetric epoxidation of allyl alcohols such as 2-propen-1-ol (R ˆ H) and trans-2-hexen-1-ol (R ˆ nPr) with solid tantalum catalysts [Ta]s
or with molecular compounds, Ti(OiPr)4 and Ta(OEt)5.
[Ta]s, CH2Cl2
O
OH
R
OH
+
tBuOH
+
tBuOOH
R
(+) -Tartrate
Entry
Catalyst
R
Metal/alcohol[a]
Alcohol
concentration
Conversion [%][b]
Yield [%][b]
ee [%][b, c]
80 (S)
1
2
3
4
5
6
7
8
9
Ti(OiPr)4
[Ti]
H
H
H
H
H
H
H
H
nPr
nPr
nPr
nPr
5/100
5/100
2/100
2/100
2/100
2/100
2/100
19/100
5/100
4/100
4/100
4/100
1.0m[d, e]
0.4m[d, e]
1.0m[d, f]
0.1m[d, f]
0.1m[f]
76
17
ca. 0.5
60
31
30
20
79
99
72
14
0.4
56
30
29
19.5
77
80
40
34
31
ca. 9 (R)
Ta(OEt)5
[Ta]#2
[Ta]#1
[Ta]#1
[Ta]#3
[Ta]#1
Ti(OiPr)4
[Ta]#2
[Ta]#2
[Ta]#2
45 (R)
85 (S)
84 (S)
83 (R)
94 (S)
84 (S)
96 (S,S)
90 (S,S)
89 (S,S)
93 (S,S)
0.1m[g]
0.4m[f]
0.1m[f]
1.0m[d, h]
0.1m[d, f]
0.1m[h]
10
11
12
48
35
35
0.1m[h, i]
[a] Molar ratio. [b] Determined after 48 h by GC (Lipodex E) with n-dodecane as an internal standard. [c] The major enantiomer obtained is shown in
parentheses. [d] With 3-Š powdered molecular sieves previously dehydrated at 3008C under vacuum. [e] At 08C; chiral inducer: (‡)-DIPT; oxidant: CHP.
[f] At 08C; chiral inducer: (‡)-DIPT; oxidant: TBHP. [g] As in entry 5, but with ( )-DIPT. [h] At 208C; chiral inducer: (‡)-DET; oxidant: TBHP. [i] As in
entry 11, but with second use of the catalyst.
0.1m while using a metal/substrate ratio of 2/100, because with
the solid catalyst the reaction medium is too thick and more
difficult to stir. Indeed, with a solid Ta catalyst, an increase in
the alcohol concentration leads to lower alcohol conversion
and yield, probably owing to the insufficient stirring, but the
enantiomeric excess is better (94% ee) and does not seem to
be related to a subsequent kinetic resolution (compare
entries 4 and 7). An increase in the metal/substrate ratio
from 2/100 to 19/100 leads to a better yield, though the yield is
not proportional to the amount of tantalum introduced
(compare entries 4 and 8). The termination of the reaction
may be explained by a poisoning of the catalytic sites either by
water generated in side reactions or by a chelating diol
produced in the ring opening of glycidol by an alcohol or
water.[6]
Silica-supported tantalum also showed good activity and
enantioselectivity for the epoxidation of trans-2-hexen-1-ol
to (2S,3S)-2-hydroxymethyl-3-propyloxirane with molecular
sieves (Table 1, entry 10; TON ˆ 10, 90% ee) or without
molecular sieves (entry 11; TON ˆ 8.5, 89% ee). For this
substrate, homogeneous catalysis with molecular Ti(OiPr)4
was very effective and enantioselective (entry 9; TON ˆ 16,
96% ee). The solid used in entry 11 was washed with CH2Cl2
after reaction and reused for a new reaction without adding
tartrate. This preliminary result shows that the catalyst can be
recycled and that almost the same results are obtained
(entry 12; TON ˆ 8, 93% ee).
supported tantalum may result from the presence of well
dispersed monomeric tantalum species on the silica surface,
which would lead to monomeric active sites. The molecular
tantalum alkoxides, Ta(OR)5, which are dimers in weakly
polar solvents[19] would lead to dimers in the presence of
tartrate and the reactants, as was proposed in the case of
titanium.[5] These molecular tantalum dimers would be poor
active sites compared to supported monomeric species.
Another important difference is the connection with the
surface, which may also provide an activation of the catalytic
site through the support.
Experimental Section
ˆ
Ta( CHCMe3)(CH2CMe3)3 (1) was prepared as described by Schrock
et al.[20] The silica used is an aerosil 200 from Degussa. It was activated at
5008C under vacuum (10 4 mbar) and is referred to as silica(500). Diethyl
(DET) and diisopropyl tartrates (DIPT) were available from Aldrich.
Anhydrous tert-butyl hydroperoxide (TBHP) in dichloromethane was
prepared by azeotropic distillation (70% THBP in water, Aldrich).[7] All
operations were carried out under an inert atmosphere (argon or vacuum).
A solution of 1 in n-pentane was used to impregnate silica(500). The solid was
filtered off and washed with n-pentane, and the amount of neopentane
evolved during the grafting reaction was determined by gas chromatog-
raphy (GC). Dry ethanol was condensed onto the solid, which was then
thermally treated at 1508C. The gas and liquid phases were trapped for GC
analysis, and the solid was dried at 1008C.
The epoxidation reactions were performed in a two-neck flask charged with
the metal alkoxide and CH2Cl2. Then DIPT or DET was introduced
(usually the natural (‡) tartrates; 1.2 ± 1.5 equiv per mol of metal). The
flask was cooled to the desired temperature and then the allyl alcohol and a
solution of hydroperoxide (cumene hydroperoxide (CHP) or TBHP;
2 equiv per mol of alcohol) were added. The reaction was stopped by
removing the catalyst from the solution by filtration. Conversions, yields,
and ee values were determined by GC with a chiral g-cyclodextrin column.
For these epoxidations, the surface tantalum and the
Sharpless molecular titanium species both present good
enantioselectivity and activity. The solid tantalum catalysts
are easily separated from the reaction medium by filtration
and can be recycled. The good catalytic activity observed for
the solids containing tantalum and the bad performances of
the silica-supported titanium catalyst are in good agreement
with our conceptual approach (Scheme 1). The activity of
Received: April 9, 1999 [Z13263IE]
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3541

COMMUNICATIONS
Keywords: asymmetric catalysis ´ epoxidations ´ heteroge-
neous catalysis ´ surface chemistry ´ tantalum
Total Synthesis of (‡)-Halichlorine:
An Inhibitor of VCAM-1 Expression**
Dirk Trauner, Jacob B. Schwarz, and
Samuel J. Danishefsky*
[1] B. E. Rossiter in Asymmetric Synthesis, Vol. 5 (Ed.: J. D. Morrison),
Academic Press, New York, 1985, p. 193.
[2] M. Bulliard, W. Shum, Proceedings of the Chiral ꢀ95 USA Symposium,
1995, p. 5.
[3] T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5974.
[4] J. N. Armor, Appl. Catal. 1991, 78, 141.
[5] M. G. Finn, K. B. Sharpless J. Am. Chem. Soc. 1991, 113, 113.
[6] R. M. Hanson, K. B. Sharpless, J. Org. Chem. 1986, 51, 1922.
[7] Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, K. B.
Sharpless, J. Am. Chem. Soc. 1987, 109, 5765.
[8] R. A. Johnson, K. B. Sharpless in Comprehensive Organic Synthesis,
Vol. 7 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford, 1991,
p. 389.
[9] A. Baiker, H. U. Blaser in Handbook of Heterogeneous Catalysis, Vol.
5 (Eds.: G. Ertl, H. Knözinger, J. Weitkamp), VCH, Weinheim, 1997,
p. 2432.
[10] G. J. Hutchings, D. F. Lee, A. R. Minihan, Catal. Lett. 1995, 33,
369.
[11] C. Cativiela, J. M. Fraile, J. I. Garcia, J. A. Mayoral, J. Mol. Catal.
1996, 112, 259.
[12] W. Adam, A. Corma, A. Martinez, C. M. Mitchell, T. I. Reddy, M.
Renz, A. K. Smertz, J. Mol. Catal. 1997, 117, 357.
[13] B. M. Choudary, V. L. K. Valli, A. D. Prasad, J. Chem. Soc. Chem.
Commun. 1990, 1186.
Vascular cell adhesion molecule-1 (VCAM-1), a member of
the immunoglobulin superfamily, monitors and regulates
leukocyte recruitment into inflamed tissue.[1] Since leukocyte
infiltration is involved in various allergic inflammatory
disorders as well as pathogenic processes such as asthma
and arteriosclerosis VCAM-1 has emerged as a potential
target for drug discovery. In principle, blockade or inhibition
of VCAM-1 could have consequences in regulating leukocyte
trafficking. Given such considerations an agent that specifi-
cally inhibits induced VCAM-1 expression could be of
particular interest. While screening for active compounds
from marine organisms Uemura and colleagues isolated a
substance from the marine sponge Halichondria okadai Ka-
dota, which they named halichlorine, and identified its
structure as 1.[2] A related structure, pinnaic acid (2), had
been isolated from an Okinawan bivalve Pinna muricata.[3]
H
[14] V. Dufaud, G. P. Niccolai, J. Thivolle-Cazat, J. M. Basset, J. Am. Chem.
Soc. 1995, 117, 15.
HOOC
5
HN
O
N
[15] This already known surface reaction[14] leads to the liberation of
neopentane (ca. 1.5 mol per mol of grafted Ta) with the formation of a
mixture of two well-defined surface species, 2a and 2b.
[16] Step 2: 2.5 mol of neopentane evolved per mol of surface
tantalum.
9
1
O
13
Me
Me
Cl
14
14
Cl
17
HO
OH
17
[17] [Ta]#1: 4.92 wt% Ta, C/Ta ˆ 8.9; [Ta]#2: 5.40 wt% Ta, C/Ta ˆ 7.2;
[Ta]#3: 5.63 wt% Ta, C/Ta ˆ 7.1. For a mixture of 3a (50%) and 3b
(50%) a theoretical value of C/Ta ˆ 7 should be observed; this is the
case for [Ta]#2 and [Ta]#3. For [Ta]#1 the higher value may be
explained by the presence of SiOEt species.
[18] R. A. Sheldon, M. Wallau, I. W. C. E. Arends, U. Schuchardt Acc.
Chem. Res. 1998, 31, 485.
[19] L. G. Hubert-Pfalzgraf, J. Guion, J. G. Riess, Bull. Soc. Chim. Fr. 1971,
11, 3855.
OH
2
1
Aside from several provocative features of halichlorine,
which might pose stimulating opportunities to the organic
chemist, this compound commands particular attention be-
cause it selectively inhibits the induced expression of VCAM-
1
1 with an IC50 of 7 mgmL . Interestingly, pinnaic acid was
[20] R. R. Schrock, J. D. Fellmann, J. Am. Chem. Soc. 1978, 100, 3359.
obtained from a screen designed to identify specific inhibitors
of cytosolic phospholipase A2 (cPLA2).
Among the challenges posed by halichlorine is that of its
total synthesis.[4] Aside from providing the setting for
addressing several interesting chemical issues, its total syn-
thesis holds the prospect of providing probe structures to
document structure ± activity relationships. Elsewhere we
[*] Prof. S. J. Danishefsky,[‡] Dr. D. Trauner, Dr. J. B. Schwarz
Laboratory for Bioorganic Chemistry
Sloan-Kettering Institute for Cancer Research
1275 York Avenue, New York, NY 10021 (USA)
Fax: (‡1)212-772-8691
E-mail: s-danishefsky@ski.mskcc.org
Further address:
‡
[ ] Department of Chemistry
Columbia University
Havemeyer Hall, New York, NY 10027 (USA)
[**] This work was supported by the National Institutes of Health (Grant
numbers: CA-28824 (S.J.D), CA-08748 (Sloan Kettering Institute
Core Grant), and NIH-F3218804 (J.B.S.)). D.T. gratefully acknowl-
edges the Schering Research Foundation, Berlin, for a postdoctoral
fellowship. We thank George Suckenick of the NMR Core Facility for
mass spectral analyses.
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