Enantioselective Palladium-Catalyzed Hydrosilylation of Styrene: Detailed Reaction Mechanism from First-Principles and Hybrid QM/MM Molecular Dynamics Simulations

The mechanism of the enantioselective hydrosilylation of styrene catalyzed by Pd0 species
generated in situ from dichloro{1-{(R)-1-[(S)-2(diphenylphosphino-κP)ferrocenyl]ethyl}-3-trimethylphenyl-5-1H-pyrazole-κN}palladium, 1, has been investigated in detail through
ab initio molecular dynamics and hybrid ab initio molecular dynamics/molecular mechanics
(QM/MM) calculations. Different QM/MM models have been adopted in order to probe the
specific steric and electronic contributions of different substituents. The catalytic cycle is
initiated by the formation of a weakly bound π-complex (ΔE ≈ −5.4 kcal/mol) under
simultaneous detachment of the pyrazole ligand. In agreement with a Chalk−Harrod
mechanism, this is followed by the migratory insertion of the hydride, which leads to a η3-coordination mode of the benzylic fragment. The significant stabilization of the allylic
intermediate (ΔE ≈ −11 kcal/mol) is responsible for the high regioselectivity of the reaction
(as well as for its enantioselectivity). The rate-determining step with an activation barrier
of 16 kcal/mol is the migration of the silyl ligand to the α-carbon of the substrate with
concomitant closure of the ligand chelate ring. This step leads to the formation of an
intermediate in which the phenyl moiety of the product remains coordinated in an η2-mode
to the palladium. The addition of trichlorosilane leads to product formation and hence to
the regeneration of the catalyst. A unimolecular reaction pathway on the other hand, in
which the transfer of the silyl ligand to the benzylic fragment is concerted with the addition
of a molecule of HSiCl3 to the catalyst, is disfavored by an activation barrier of ∼30 kcal/mol.