Concentration-Flux-Steered Mechanism Exploration with an Organocatalysis Application

TL;DR

This paper introduces an automated algorithm that dynamically explores kinetically relevant regions of a chemical reaction network by modeling concentration fluxes, demonstrated on a proline-catalyzed Michael addition, providing detailed mechanistic insights.

Contribution

The authors present a novel automated exploration algorithm that identifies and investigates kinetically accessible reaction pathways during first-principles network exploration.

Findings

Detailed mechanistic picture of the Michael addition process.

Algorithm effectively identifies kinetically relevant reaction regions.

Enhanced understanding of complex catalytic reaction networks.

Abstract

Investigating a reactive chemical system with automated reaction network exploration algorithms provides a more detailed picture of its chemical mechanism than what would be accessible by manual investigation. In general, exploration algorithms cannot uncover reaction networks exhaustively for feasibility reasons. They should therefore decide which part of a network is kinetically relevant under some external conditions given. Here, we propose an automated algorithm that identifies and explores kinetically accessible regions of a reaction network on the fly by explicit modeling of concentration fluxes through an (incomplete) reaction network that is emerging during automated first-principles exploration. Key compounds are automatically identified and selected for the continuation of the exploration. As an example, we explore the reaction network of the multi-component proline-catalyzed Michael addition of propanal and nitropropene. Our algorithm provides a mechanistic picture of the Michael addition in unprecedented detail.