Solution-Phase Conformational/Vibrational Anharmonicity in Comonomer Incorporation Polyolefin Catalysis.

The prediction of comonomer incorporation statistics in polyolefin catalysis necessitates an accurate calculation of free energies corresponding to monomer binding and insertion, often requiring sub-kcal/mol resolution to resolve experimental free energies. Batch reactor experiments are used to probe incorporation statistics of ethene and larger α-olefins for three constrained geometry complexes which are employed as model systems. Herein, over 6 ns of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics is performed in combination with the zero-temperature string method to characterize the solution-phase insertion barrier and to analyze the contributions from conformational and vibrational anharmonicity arising both in vacuum and in solution. Conformational sampling in the solution-phase results in 0-2 kcal/mol corrections to the insertion barrier which are on the same scale necessary to resolve experimental free energies. Anharmonic contributions from conformational sampling in the solution phase are crucial energy contributions missing from static density functional theory calculations and implicit solvation models, and the accurate calculation of these contributions is a key step toward the quantitative prediction of comonomer incorporation statistics.

Embedded Mean-Field Theory for Solution-Phase Transition-Metal Polyolefin Catalysis.

Decreasing the wall-clock time of quantum mechanics/molecular mechanics (QM/MM) calculations without sacrificing accuracy is a crucial prerequisite for widespread simulation of solution-phase dynamical processes. In this work, we demonstrate the use of embedded mean-field theory (EMFT) as the QM engine in QM/MM molecular dynamics (MD) simulations to examine polyolefin catalysts in solution. We show that employing EMFT in this mode preserves the accuracy of hybrid-functional DFT in the QM region, while providing up to 20-fold reductions in the cost per SCF cycle, thereby increasing the accessible simulation time-scales. We find that EMFT reproduces DFT-computed binding energies and optimized bond lengths to within chemical accuracy, as well as consistently ranking conformer stability. Furthermore, solution-phase EMFT/MM simulations provide insight into the interaction strength of strongly coordinating and bulky counterions.

Iron-Catalyzed Oxyfunctionalization of Aliphatic Amines at Remote Benzylic C-H Sites.

We report the development of an iron-catalyzed method for the selective oxyfunctionalization of benzylic C(sp(3))-H bonds in aliphatic amine substrates. This transformation is selective for benzylic C-H bonds that are remote (i.e., at least three carbons) from the amine functional group. High site selectivity is achieved by in situ protonation of the amine with trifluoroacetic acid, which deactivates more traditionally reactive C-H sites that are α to nitrogen. The scope and synthetic utility of this method are demonstrated via the synthesis and derivatization of a variety of amine-containing, biologically active molecules.