Nucleophilic substitution vs elimination reaction of bisulfide ions with substituted methanes: exploration of chiral selectivity by stereodirectional first-principles dynamics and transition state theory

TL;DR

This study uses first-principles dynamics and transition state theory to explore how molecular orientation influences nucleophilic substitution and elimination reactions of bisulfide ions with chiral substituted methanes, revealing enantiomer-specific reactivity.

Contribution

It demonstrates for the first time the impact of molecular orientation on reaction pathways and stereoselectivity in chiral molecules using advanced simulation techniques.

Findings

Orientation affects reaction pathways and stereoselectivity.

Enantiomers exhibit different reactivities in SN2 reactions.

Alternative reaction pathways depend on molecular chirality.

Abstract

Control of molecular orientation is emerging as crucial for the characterization of the stereodynamics of kinetics processes beyond structural stereochemistry. The special role played in chiral discrimination phenomena has been particularly emphasized by the authors after their extensive probes of experimental control of molecular alignment and orientation. In this work, the role of the orientation has been demonstrated for the first time in first-principles molecular dynamics simulations: stationary points characterized on potential energy surfaces have been calculated for the study of chemical reactions occurring between the bisulfide anion HS- and oriented prototypical chiral molecules CHFXY (where X = CH3 or CN and Y = Cl or I). The important reaction channels are those corresponding to bimolecular nucleophilic substitution (SN2) and to bimolecular elimination (E2): their relative role has been assessed and alternative pathways due to the mirror forms of the oriented chiral molecule are revealed by the different reactivity of the two enantiomers of CHFCNI in SN2 reaction.