Journal of the American Chemical Society
COMMUNICATION
and SI). For most of the enamides studied (23ꢀ25) we found
good to high enantioselectivities, while simple alkenes (27ꢀ28)
were hydrogenated with moderate ee’s. These results are in
agreement with the observation that the hydrogen bond formed
between the NH of the substrate and the carbonyl group of the
cofactor plays an important role in the enantioselectivity deter-
mining step of the hydrogenation reaction.
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In conclusion, we demonstrate in this paper that asymmetric
hydrogenation can be efficiently achieved by using an achiral
ligand in combination with a chiral cofactor.14 The current
system contains achiral bisphosphine ligand 1, coordinated to a
rhodium center, which is embedded within an anion binding
pocket. The pocket strongly binds cofactors—anions of chiral
carboxylic acids—allowing for quick, synthesis-free modulation
of the enantioselectivity of the catalyst. This strategy afforded
good to excellent enantioselectivities (ee up to 99%) for the
hydrogenation of several alkenes, demonstrating its potential.
Interestingly, even when using a mixture of 12 cofactors the
selectivity was high, which suggests that catalysis is dominated by
the best cofactor, allowing a deconvolution strategy for rapid
identification of the best cofactor. Thus, catalyst optimization by
noncovalent binding of simple cofactors expands the number of
supramolecular approaches applicable to the search for better
catalysts for challenging chemical transformations. Current ef-
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order to gain better understanding and for the rational extension
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’ ASSOCIATED CONTENT
S
Supporting Information. Details concerning catalytic
b
studies, binding studies, X-ray structure elucidation, DFT stud-
ies, experimental procedures, and spectral data for new com-
pounds, including images of H, 19F, 13C, and NOESY NMR
1
spectra. This material is available free of charge via the Internet at
(11) For thiurea-functionalized cofactors we observed inhibition of
the reaction when a larger excess of the cofactor was used, presumably
due to partial deactivation of the catalyst due to sulfur coordination at
the rhodium center.
’ AUTHOR INFORMATION
Corresponding Author
(12) Wieland, J.; Breit, B. Nat. Chem. 2010, 2, 832–837.
(13) For an example of the influence of the substrateꢀcatalyst
hydrogen bonding interactions on enantioselectivity, see: Breuil, P.-A. R.;
Patureau, F. W.; Reek, J. N. H. Angew. Chem., Int. Ed. 2009, 48, 2162–2165.
(14) For related studies in which chiral cofactors are bound in a
porphyrin based cage leading to low ee in catalytic sulfoxidation, see: (a)
Lee, S. J.; Cho, S.-H.; Mulfort, K. L.; Tiede, D. M.; Hupp, J. T.; Nguyen,
S. T. J. Am. Chem. Soc. 2008, 130, 16828–16829. (b) Merlau, M. L.;
Mejia, M.; del, P.; Nguyen, S. T.; Hupp, J. T. Angew. Chem., Int. Ed. 2001,
113, 4369–4372.
’ ACKNOWLEDGMENT
We kindly acknowledge the NRSC-C for financial support,
Dr. B. de Bruin and Dr. J. I. van der Vlugt for helpful discussions,
Dr. L. Rupnicki for valuable suggestions, F. Terrade for assistance
with HPLC and GC analysis, and Y. Gumrukcu for assistance
with NMR experiments.
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