C O M M U N I C A T I O N S
Cartesian coordinates for the lowest energy structures of B3, E3, G3E,
and G3Z are available in the SI.
In summary, the Q2MM method requires substantial development
times for each reaction type under study but, in return for this
investment, yields a fast tool with high accuracy. The excellent
performance (R2 > 0.90) of the virtual screening of a ligand library
for the enantioselective catalytic hydrogenation of enamides suggests
that similar reaction-specific force fields can be derived for many other
enantioselective reactions. Future applications of the strategy to other
industrially important reactions as well as much larger virtual libraries
will explore the generality of this approach, which has the potential to
fundamentally change the process of ligand selection from a trial-and-
error driven process to the combination of virtual screening and
experimental confirmation that is used extensively in drug discovery.
Finally, the possibility of rapidly predicting the enantioselectivity of
related reactions not only permits ligand selection but also adds
significant value to the wealth of available information for organo-
metallic reaction mechanisms. As such, it could provide a novel
mechanistic tool through the quantitative rather than more common
qualitative use of stereochemistry as a mechanistic probe.
Figure 1. Ligands (A-M) and substrates (1-7) used in test set. Substrates
3-7 are in the Z orientation unless otherwise specified.
Acknowledgment. We gratefully acknowledge the allocation
of computer resources by the Center for Research Computing at
the University of Notre Dame and partial support of this work by
Procter & Gamble Pharmaceuticals. P.J.D. is the recipient of a
Schmitt Fellowship from the University of Notre Dame.
Supporting Information Available: Computational details, selected
Cartesian coordinates, and detailed statistical analysis of the calculated
data points. This material is available free of charge via the Internet at
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