Asymmetric dihydroxylation with silica-anchored alkaloids

Article abstract of DOI:10.1039/a706605h

Diols with excellent enantiomeric excesses are obtained from unfunctionalised alkenes in high yields by osmium-catalysed dihydroxylationsusingsilica-boundpyrimidineandpyrazino-pyridazine ligands.

Full text of DOI:10.1039/a706605h

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Asymmetric dihydroxylation with silica-anchored alkaloids
Carsten Bolm,* Astrid Maischak and Arne Gerlach
Institut f u¨ r Organische Chemie, RWTH Aachen, Professor-Pirlet-Strasse 1, D-52056 Aachen, Germany
Diols with excellent enantiomeric excesses are obtained from
unfunctionalised alkenes in high yields by osmium-catalysed
dihydroxylationsusingsilica-boundpyrimidineandpyrazino-
pyridazine ligands.
In the AD of styrene and stilbene, exceedingly high
enantioselectivities were achieved with heterogeneous silica-
anchored ligands 1a and 1c having ether and ester linkers,
respectively. A slightly lower asymmetric induction was
observed when amido linked 1b was applied (Table 1, entry 3).
Presumably, residual amino groups on the silica surface or the
amido linker itself have a negative influence, giving diols with
reduced enantiomeric excess. Support of this hypothesis was
gained in AD experiments performed with alkaloid-free amino
functionalized silica gel. The rapid formation of racemic diol
revealed the high catalytic activity of the support.
Under homogeneous conditions pyrimidine ligands are most
suitable for the enantioselective dihydroxylation of aliphatic,
terminal alkenes. Therefore, AD reactions of dec-1-ene were
performed with silica-supported pyrimidines 2a and 2b (Table 1,
entries 5 and 6). Catalyses with both ligands afforded the
The Sharpless asymmetric dihydroxylation (AD) is an efficient
catalytic method for the enantioselective oxidation of un-
1
2
functionalised alkenes. Since its discovery in 1988 the catalyst
3
system has been continuously optimised, so that now almost
any alkene can be transformed to the corresponding diol with
high enantioselectivity. In order to ease the recovery of the
ligands after the catalysis, the use of various polymer-supported
cinchona alkaloids has been studied.4 Most of the insoluble
ligands are easily handled but suffer from disadvantages, such
as longer reaction times and lower enantioselectivity. Recently,
–7
6
7
we and others introduced soluble polymer-supported alka-
loids with MeO-PEG tethers which gave catalysts with similar
reactivity and enantioselectivity as those reported for the
original Sharpless system. Ligand recovery was easily accom-
plished by addition of ethereal solvents to the reaction mixture
followed by filtration of the precipitated alkaloid. In our
1
R O
ODHQD
6
approach, the MeO-PEG attachment was designed such that
N
negative steric interactions between the polymer backbone and
the alkaloid moiety were minimised. We now report on the
anchoring of this type of specifically modified cinchona
alkaloid on insoluble inorganic carriers based on silica. In
contrast to organic polymers, this kind of heterogeneous support
offers a variety of possible applications due to its mechanical
and thermal stability.
N
N
N
ODHQD
2
R O
The polysiloxane-anchored bis(9-O-dihydroquinidinyl)py-
razinopyridazine 1 and bis(9-O-dihydroquinidinyl)pyrimidine 2
were synthesised from the corresponding phenols (R , R = H)
1
a R1
R2 = H or R1
=
silica gel
1
2
6
O
and commercial functionalised silica† using standard acylation
or nucleophilic substitution reactions.
The catalysed asymmetric dihydroxylations of representative
b R1
N
H
=
silica gel
O
alkenes were performed under standard reaction conditions in
O
t
Bu OH–H
2
O (1:1) using K
OsO (OH)
3
[Fe(CN)
and 2 mol% of immobilised
6 2 3
]–K CO as oxidant,
R2 = R1 or
0.5–1 mol% of K
2
2
4
HO
ligand. Mechanical stirring was applied in order to avoid silica
deterioration. The most significant results are summarised in
Table 1.
O
O
OH
O
c R1
=
silica gel
O
Table 1 Enantioselectivities in the AD of various alkenesa
O
R2 = R1 or
Yield
(%)
Ee
(%)
Con-
figuration
HO
b
Entry Alkene
Ligand
O
1
2
3
4
5
6
7
trans-PhCHNCHPh
1a
1a
1b
1c
2a
2b
2b
77
93
93
92
51
53
62
99 (99) (R,R)
98 (99) (R)
PhCHNCH
PhCHNCH
PhCHNCH
2
2
2
ODHQD
90
97
(R)
(R)
N
1
R O
C
C
8
H
17CHNCH
17CHNCH
2
84 (89) (R)
61 (R)
70 (92) (R)
N
8
H
2
ODHQD
O
t
Bu CHNCH
2
2a R1
=
=
a
AD experiments as per typical protocol (see text). b Determined either by
silica gel
silica gel
comparison of the specific rotation with the authentic samples or by HPLC
using a chiral stationary phase [refs. 3(a), 4(f), 6]. The ee values of products
which were obtained from catalyses with non-polymer supported DHQD
ligands [ref. 3(b)] are given in parentheses.
b R1
N
H
O
Chem. Commun., 1997
2353

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(ii) The new silica-bound alkaloids can be quantitatively
recovered by simple filtration. (iii) Recycled ligands give
catalysts which perform several times without loss of activity
and enantioselectivity. (iv) Consecutive use of the immobilised
ligands in AD reactions is possible but requires the addition of
small quantities of osmium after each run. If no metal is added
the enantioselectivity remains high but the catalyst activity is
reduced.
1
1
a
c
1
00
9
5
0
9
This research was supported in part by grants from the BMBF
and the Fonds der Chemischen Industrie.
85
80
75
70
Footnotes and References
*
†
E-mail: carsten.bolm@rwth-aachen.de
The chloropropyl functionalised silica (2.5% chloride content) was
2
1
obtained from Aldrich. Propylamino (0.19 mmol g ) and diol function-
2
1
alised (0.35 mmol g ) polysiloxanes were purchased from Schuller. A
double attachment of 1 onto the silica surface via the two phenolic hydroxy
groups cannot be excluded.
1
2
3
4
Run
5
6
7
Fig. 1 Enantioselectivities in consecutive AD reactions of styrene using
silica-supported alkaloids 1a and 1c
1
2
H. C. Kolb, S. VanNieuwenhze and K. B. Sharpless, Chem. Rev., 1994,
4, 2483.
E. N. Jacobsen, I. Mark o´ , W. S. Mungall, G. Schroeder and K. B.
9
corresponding diols in moderate yield with enantiomeric
excesses of 84 and 61%, respectively. The former value
compares well to the one obtained with the original homoge-
neous Sharpless system (89% ee).
Sharpless, J. Am. Chem. Soc., 1988, 110, 1968.
3 (a) H. Becker and K. B. Sharpless, Angew. Chem., 1996, 108, 447;
Angew. Chem., Int. Ed. Engl., 1996, 35, 448; (b) H. Becker, S. B. King,
M. Taniguchi, K. P. M. Vanhessche and K. B. Sharpless, J. Org. Chem.,
1
995, 60, 3940; (c) K. B. Sharpless, W. Amberg, Y. L. Bennani,
In order to examine the stability of the catalyst and the
possibility of ligand recovery, 1a and 1c were used in
consecutive AD reactions of styrene. As shown in Fig. 1, silica-
supported alkaloid 1a was used seven times without significant
loss of enantioselectivity. The enantiomeric excess of the diol
stayed in the range of 97–98%, and the chemical yields were
excellent. In contrast, in AD reactions with silica-attached 1c
the efficiency of the catalysis decreased with each run.
Presumably, parts of the alkaloid were lost in each recycling
process due to a minor ester hydrolysis under the basic reaction
conditions. In order to ensure the presence of sufficient amounts
G. A. Crispino, J. Hartung, K.-S. Jeong, H.-L. Kwong, K. Morikawa,
Z.-M. Wang, D. Xu and X.-L. Zhang, J. Org. Chem., 1992, 57, 2768; (d)
E. J. Corey, A. Guzman-Perez and M. C. Noe, J. Am. Chem. Soc., 1995,
1
17, 10805.
4
(a) B. M. Kim and K. B. Sharpless, Tetrahedron Lett., 1990, 31, 3003; (b)
D. Pini, A. Petri, A. Nardi, C. Rosini and P. Salvadori, Tetrahedron Lett.,
1991, 32, 5175; (c) B. B. Lohray, E. Nandanan and V. Bhushan,
Tetrahedron Lett., 1994, 35, 6559; (d) C. E. Song, E. J. Roth, S.-y. Lee
and I. O. Kim, Tetrahedron: Asymmetry, 1995, 6, 2687; (e) D. Pini,
A. Petri and P. Salvadori, Tetrahedron, 1994, 50, 11321; (f) A. Petri,
D. Pini, S. Rapaccini and P. Salvadori, Chirality, 1995, 7, 580; (g)
C. E. Song, J. W. Yang, H. J. Ha and S.-y. Lee, Tetrahedron: Asymmetry,
of osmium in the reaction mixture, 0.5–1 mol% of K
(OH) was added before each run in the experiments
2
Os-
1
1
996, 7, 645; (h) P. Salvadori, D. Pini and A.Petri, J. Am. Chem. Soc.,
997, 119, 6929 and references cited therein.
O
2
4
described above. Without this addition, a considerable decrease
in activity was observed, indicating metal leaching during
catalyst recovery. For example, in consecutive AD reactions of
styrene in the presence of 1a without the addition of osmium,
the diol yield dropped from 93% in the first run to 50 and 34%
yield in the second and third run, respectively. Even under these
very unfavourable conditions, and despite the metal loss, the
catalysis still benefits from the phenomenon of ‘ligand
5
For examples of other silica-supported alkaloids see: B. B. Lohray,
E. Nandanan and V. Bhushan, Tetrahedron: Asymmetry, 1996, 7, 2805;
C. E. Song, J. W. Yang and H.-J. Ha, Tetrahedron: Asymmetry, 1997, 8,
841.
6 C. Bolm and A. Gerlach, Angew. Chem., 1997, 109, 773; Angew. Chem.,
Int. Ed. Engl., 1997, 36, 773.
7
H. Han and K. D. Janda, J. Am. Chem. Soc., 1996, 118, 7632; H. Han and
K. D. Janda, Tetrahedron Lett., 1997, 38, 1527; H. Han and K. D. Janda,
Angew. Chem., 1997, 109, 1835; Angew. Chem., Int. Ed. Engl., 1997, 36,
8
acceleration’ and gives the products with high enantiomeric
1
731.
D. J. Berrisford, C. Bolm and K. B. Sharpless, Angew. Chem., 1995, 107,
159; Angew. Chem., Int. Ed. Engl., 1995, 34, 1050.
excess (run 1: 98% ee; run 2: 98% ee; run 3: 95% ee).
The results of this investigation can be summarised as
follows. (i) The enantioselectivities in these heterogeneous AD
reactions are excellent, and diols with up to 99% ee are formed.
8
1
Received in Cambridge, UK, 10th September 1997; 7/06605H
2354
Chem. Commun., 1997