The ruthenium-catalyzed asymmetric hydrogenation of simple ketones to generate enantiopure alcohols is an important process widely used in the fine chemical, pharmaceutical, fragrance, and flavor industries. Chiral diphosphine-RuCl2-1,2-diamine complexes are effective catalysts for the reaction giving high chemo- and enantioselectivity. However, no diphosphine-RuCl2-1,2-diamine complex has yet been discovered that is universal for all kinds of ketone substrates, and the ligands must be carefully chosen for each substrate. The procedure of finding the best ligands for a specific substrate can be facilitated by using virtual screening as a complement to the traditional experimental screening of catalyst libraries. We have generated a transition state force field (TSFF) for the ruthenium-catalyzed asymmetric hydrogenation of simple ketones using an improved Q2MM method. The developed TSFF can predict the enantioselectivity for 13 catalytic systems taken from the literature, with a mean unsigned error of 2.7 kJ/mol.
Ferrocene derivatives have a wide
range of applications, including
as ligands in asymmetric catalysis, due to their chemical stability,
rigid backbone, steric bulk, and ability to encode stereochemical
information via planar chirality. Unfortunately, few of the available
molecular mechanics force fields incorporate parameters for the accurate
study of this important building block. Here, we present a MM3* force
field for ferrocenyl ligands, which was generated using the quantum-guided
molecular mechanics (Q2MM) method. Detailed validation by comparison
to DFT calculations and crystal structures demonstrates the accuracy
of the parameters and uncovers the physical origin of deviations through
excess energy analysis. Combining the ferrocene force field with a
force field for Pd–allyl complexes and comparing the crystal
structures shows the compatibility with previously developed MM3*
force fields. Finally, the ferrocene force field was combined with
a previously published transition-state force field to predict the
stereochemical outcomes of the aminations of Pd–allyl complexes
with different amines and different chiral ferrocenyl ligands, with
an R
2 of ∼0.91 over 10 examples.
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