1604
B. Wieczorek et al. / Tetrahedron Letters 52 (2011) 1601–1604
would have been 22% at 18% conversion. This proof-of-principle
experiment shows that the CALB-8 beads function both as racemi-
zation and enantioselective acylation catalysts. To achieve a suc-
cessful DKR the partial inhibition of the lipase with the
ruthenium catalyst 8 has to be fine-tuned.
References and notes
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In summary this Letter reports the first example of a heteroge-
neous bifunctional catalytic system, combining the catalytic prop-
erties of an organometallic catalyst (racemization) with those of an
enzyme (enantioselective acylation). In order to synthesize the
bifunctional catalyst, complex 8 was anchored covalently to CALB
beads, thereby demonstrating the reactivity of selective serine
hydrolase inhibitors, such as phosphonate 8, towards heteroge-
nized lipases. Independently, the experiments showed that the
CALB-8 beads were catalytically active in the racemization of (S)-
1-phenylethanol with complete racemization after 24 h, and that
these same beads were able to catalyze the enantioselective acyla-
tion of 1-phenylethanol (kinetic resolution). Even though the
development is at an early stage, we believe that the concept of
using site-selective reagents on immobilized enzymes to generate
multifunctional catalytic materials is general for many classes of
enzymes and for various catalytic reactions. In the present case,
we are confident that changing the ratio between ruthenium inhib-
itor complex 8 and CALB beads will allow for the optimization of
the catalytic properties of the bifunctional catalytic material.
Ongoing studies are aimed at such an optimization, and at practical
use in DKR and recycling of these materials.
Acknowledgements
The authors thank the Swedish Research Council, INTENANT,
the National Research School Combination Catalysis, NRSC-C, the
EU NoE IDECAT and Utrecht University for financial support.
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M.; van Koten, G. Eur. J. Inorg. Chem. 2010, 1929–1938; (b) Fabbirizzi, P.; Cicchi,
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10. See Supplementary data for experimental details.
Supplementary data
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Supplementary data associated with this article can be found, in