In defense of the catalytic asymmetric cis dihydroxylation of olefins utilizing insoluble polymeric ligands [6]

Full text of DOI:10.1021/ja970735c

J. Am. Chem. Soc. 1997, 119, 6929-6930
In Defense of the Catalytic Asymmetric Cis
6929
Dihydroxylation of Olefins Utilizing Insoluble
Polymeric Ligands
Piero Salvadori,* Dario Pini, and Antonella Petri
Centro di Studio del CNR per le Macromolecole
Stereordinate ed Otticamente AttiVe
Dipartimento di Chimica e Chimica Industriale
UniVersita` di Pisa
Via Risorgimento 35, 56126 Pisa, Italy
ReceiVed March 7, 1997
A recent report1 dealing with the catalytic asymmetric
dihydroxylation2 of olefins using soluble polymer-bound (SPB)
ligands prompts this paper as a sequel to our work3 using
insoluble polymer-bound (IPB) Cinchona alkaloid ligands. We
provide evidence that suggests that the IPB ligands are competi-
tive with the SPB systems and offer potential for significant
industrial application.
Figure 1. Functional monomer 1, containing different Cinchona
alkaloid derivatives.
For an easier comparison between the homogeneous and
heterogeneous processes, we synthesized3c the functional mono-
mer 1a containing the 4-chlorobenzoate group (CLB) (Figure
1), used also by Sharpless as chiral ligand in the homogeneous
phase reaction.4
Scheme 1
Monomer 1a was copolymerized3c with ethyleneglycol
dimethacrylate and hydroxyethyl methacrylate, providing poly-
mer poly-1a (Scheme 1), which was continuously extracted in
a Soxhlet device to remove any trace of monomer and soluble
material.
The insoluble fraction of the polymer was used in the cis
dihydroxylation reaction in the heterogeneous phase following
the experimental procedure adopted for the homogeneous
t
process:5a K3Fe(CN)6:K2CO3 1:1 in BuOH:H2O 1:1 as cooxi-
dant, 0.5-1% of OsO4, and 10-25% of poly-1a, calculated
from the incorporated alkaloid, which is exactly the same
catalytic amount of polymeric ligand used by Sharpless5b and
by Janda.1 We chose styrene, an extensively used molecule
both in homogeneous and heterogeneous processes, as a suitable
substrate to show differences in terms of enantioselectivity and
reactivity. (R)-(-)-1-Phenyl-1,2-ethanediol was obtained after
20 h in 75% isolated yield and an enantiomeric excess (ee) of
65% (entry 1, Table 1).
The effect recycling the catalyst had on the yield and the ee
of the reaction was next examined. The polymeric chiral
catalytic precursor was quantitatively recovered at the end of
the reaction by filtration, avoiding any chemical or chromato-
graphic separation from the reaction products, necessary when
the chiral catalyst is soluble in the reaction medium. Some OsO4
was lost to the mother liquor as well as the methanol used to
wash the resin. Therefore, a small amount (0.2% of OsO4) was
added to completely regenerate the reaction conditions. The
above procedure was repeated 5 times, and the results obtained
are shown in Figure 2, where the plots of the percentages of
Table 1. Heterogeneous Catalytic Asymmetric Dihydroxylationa of
Olefins Using Different Cinchona Alkaloid Derived Insoluble
Ligands
(1) Han, H.; Janda, K. D. J. Am. Chem. Soc. 1996, 118, 7632.
(2) For a review, see: (a)Lohray, B. B. Tetrahedron: Asymmetry 1992,
3, 1317. (b) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric
Dihydroxylation. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH:
Weinheim, 1993; pp 227-272. (c) Kolb, H. C.; Van Nieuwenhze, M. S.;
Sharpless, K. B. Chem. ReV. 1994, 94, 2483.
(3) (a) Pini, D.; Petri, A.; Nardi, A.; Rosini, C.; Salvadori, P. Tetrahedron
Lett. 1991, 32, 5175. (b) Pini, D.; Petri, A.; Salvadori, P. Tetrahedron:
Asymmetry 1993, 4, 2351. (c) Pini, D.; Petri, A.; Salvadori, P. Tetrahedron
1994, 50, 11321. (d) Petri, A.; Pini, D.; Salvadori, P. Tetrahedron Lett.
1995, 36, 1549. (e) Petri, A.; Pini, D.; Rapaccini, S.; Salvadori, P. Chirality
1995, 7, 580.
(4) Jacobsen, E. N.; Marko´, I.; Mungall, W. S.; Schro¨der, G.; Sharpless,
K. B. J. Am. Chem. Soc. 1988, 110, 1968.
(5) (a) Kwong, H.; Sorato, C.; Ogino, Y.; Chen, H.; Sharpless, K. B.
Tetrahedron Lett. 1990, 31, 2999. (b) Kim, B. M.; Sharpless, K. B.
Tetrahedron Lett. 1990, 31, 3003.
a The asymmetric dihydroxylation reactions were run for 20 h at 0
°C using as secondary oxidant K3Fe(CN)6 in tBuOH:H2O 1:1. b Isolated
yield by column chromatography. c The ee values were determined by
HPLC analysis of the diols.3e In parentheses, the ee values obtained
by the reaction in the homogeneous phase, using as chiral catalytic
ligands the 4-chlorobenzoate ester,4 the 9-O-phenanthryl ether6 and the
phthalazine ether9 of dihydroquinidine.
pure recovered diol and ee vs the number of recycles of the
catalyst are reported.
The extent of dihydroxylation of styrene as well as the ee
values were also investigated by direct analysis of the reaction
S0002-7863(97)00735-X CCC: $14.00 © 1997 American Chemical Society

6930 J. Am. Chem. Soc., Vol. 119, No. 29, 1997
Communications to the Editor
7 h), without the slow addition of the olefin. When NMO was
used as cooxidant, lower3c enantioselectivity was observed. The
slow addition of the olefin (20-24 h in many cases) to the
reaction mixture7 resulted in some improvement; however, ee
values were lower than those obtained by using K3Fe(CN)6, an
effect which is presumably the manifestation of the “second
cycle” problem observed by Sharpless.8
As far as the enantioselectivity is concerned, the ee extent,
determined periodically by HPLC on chiral stationary phase,
was practically constant in the presence of poly-1a and
comparable to that obtained with homogeneous ligands employ-
ing the soluble model compound 2. When poly-1b and poly-
1c are used,3d,e synthesized from monomers 1b and 1c having
different substituents in the alkaloidic moiety, the diol was
obtained with ee of 68% and 91%, respectively (Table 1, entries
2 and 3). A similar trend has been observed for the reaction
using homogeneous ligands.2 In fact, Sharpless has demon-
strated that replacing the CLB group used in the original
catalytic procedure with phenanthryl ether6 (PHN) or a phthala-
zine derivative9 (PHAL) led to a considerable increase in the
enantioselectivity of the reaction. As seen in Table 1, a number
of olefins having different structures gave products with useful
ee values.
Taking into account the results obtained, some closing
remarks can be drawn. The polyhydroxy methacrylic backbone
offers a favorable microenvironment to the chiral catalytic sites
confirming that once an appropriate support compatible with
the reaction medium is found, the reactivity with soluble or
insoluble ligands is very similar. This concept is illustrated by
the curves in Figure 3. It is also evident that insoluble polymers
poly-1(a-c) show the following attractive features: (i) short
reaction times, without slow addition of the olefin; (ii) easy
recovery of the catalyst by simple filtration and the ability to
be recycled repeatedly without significant loss of reactivity or
enantioselectivity; (iii) a high extent of enantioselectivity. In
addition this polymeric system is very flexible, since the
connecting site to the polymeric chain leaves the hydroxyl group
of the alkaloidic moiety (R ) H, Figure 1) accessible for the
modification, which plays a fundamental role in the asymmetric
dihydroxylation process.10
Figure 2. Plot of yields and ee values vs recycles of polymer poly-1a
catalyzed dihydroxylation of styrene.
Figure 3. Conversion vs time curve of polymer poly-1a and soluble
model compound 2 catalyzed dihydroxylation of styrene.
mixture using HPLC on a chiral DAICEL column, coupled with
UV and CD detectors. The diol enantiomers, chemical impuri-
ties, and unreacted styrene were easily and directly monitored
without any isolation of the products. In Figure 3 the conversion
vs time plot of the reaction catalyzed by insoluble poly-1a is
reported together with that for the reaction in the presence of
2, a soluble model compound of the monomeric unit.
In conclusion, the results obtained in the present investigation
demonstrate that reliable insoluble polymeric ligands can be
designed for the cis dihydroxylation of olefins. These ligands
retain the advantages of their soluble monomer counterparts in
terms of activity, enantioselectivity, and allowable reaction
conditions. Furthermore, the ease of handling and ability to
recycle make these polymer-bound ligands ideal for both large
and small scale synthesis.
It is evident that the dihydroxylation rate in the presence of
poly-1a is very similar to that with the soluble analog 2 and
the conversion is over 80% within a few hours, for both the
homogeneous and the heterogeneous ligands. In our previous
work, we have adopted the standard time reported for the
homogeneous reaction5a,6 (20-24 h) in order to compare
different polymeric systems or cooxidants. We have already
reported3b that by using a cross-linked polystyrene polymer and
N-methylmorpholine N-oxide (NMO) as cooxidant, high dihy-
droxylation yields can be obtained in shorter reaction times (max
JA970735C
(7) Lohray, B. B.; Kalantar, T. H.; Kim, B. M.; Park, C. Y.; Shibata, T.;
Wai, J. S. M.; Sharpless, K. B. Tetrahedron Lett. 1989, 30, 2041.
(8) Wai, J. S. M.; Marko´, I.; Svendsen, J. S.; Finn, M. G.; Jacobsen, E.
N.; Sharpless, K. B. J. Am. Chem. Soc. 1989, 111, 1123.
(9) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K.; Kwong, H.; Morikawa, K.; Wang, Z.; Xu, D.; Zhang,
X. J. Org. Chem. 1992, 57, 2768.
(6) Sharpless, K. B.; Amberg, W.; Beller, M.; Chen, H.; Hartung, J.;
Kawanami, Y.; Lubben, D.; Manoury, E.; Ogino, Y.; Shibata, T.; Ukita, T.
J. Org. Chem. 1991, 56, 4585.
(10) After our work was submitted for publication, a paper appeared
which reported new and more efficient SPB ligand: Han, H.; Janda, K. D.
Tetrahedron Lett. 1997, 38, 1527.