A DFT-Based Computational-Experimental Methodology for Synthetic Chemistry: Example of Application to the Catalytic Opening of Epoxides by Titanocene

A novel DFT-based
Reaction Kinetics (DFT-RK) simulation approach, employed in combination
with real-time data from reaction monitoring instrumentation (like
UV–vis, FTIR, Raman, and 2D NMR benchtop spectrometers), is
shown to provide a detailed methodology for the analysis and design
of complex synthetic chemistry schemes. As an example, it is applied
to the opening of epoxides by titanocene in THF, a catalytic system
with abundant experimental data available. Through a DFT-RK analysis
of real-time IR data, we have developed a comprehensive mechanistic
model that opens new perspectives to understand previous experiments.
Although derived specifically from the opening of epoxides, the prediction
capabilities of the model, built on elementary reactions, together
with its practical side (reaction kinetics simulations of real experimental
conditions) make it a useful simulation tool for the design of new
experiments, as well as for the conception and development of improved
versions of the reagents. From the perspective of the methodology
employed, because both the computational (DFT-RK) and the experimental
(spectroscopic data) components can follow the time evolution of several
species simultaneously, it is expected to provide a helpful tool for
the study of complex systems in synthetic chemistry.