  Exploring large chemical reaction networks with automated exploration
approaches and accurate quantum chemical methods can require prohibitively
large computational resources. Here, we present an automated exploration
approach that focuses on the kinetically relevant part of the reaction network
by interweaving (i) large-scale exploration of chemical reactions, (ii)
identification of kinetically relevant parts of the reaction network through
microkinetic modeling, (iii) quantification and propagation of uncertainties,
and (iv) reaction network refinement. Such an uncertainty-aware exploration of
kinetically relevant parts of a reaction network with automated accuracy
improvement has not been demonstrated before in a fully quantum mechanical
approach. Uncertainties are identified by local or global sensitivity analysis.
The network is refined in a rolling fashion during the exploration. Moreover,
the uncertainties are considered during kinetically steering of a rolling
reaction network exploration. We demonstrate our approach for
Eschenmoser-Claisen rearrangement reactions. The sensitivity analysis
identifies that only a small number of reactions and compounds are essential
for describing the kinetics reliably, resulting in efficient explorations
without sacrificing accuracy and without requiring prior knowledge about the
chemistry unfolding.
