Substituent Effects on Sulfur Phenolate Exchange Reactions: Reactivity and Bonding Analysis

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Green Chemistry

Background:

• The Sulfur Phenolate Exchange (SuPhenEx) reaction is a fluorine-free alternative to Sulfur Fluoride Exchange (SuFEx) click chemistry.
• It utilizes nitrophenolate as a leaving group, presenting a synthetically viable and environmentally conscious approach.
• The molecular-level reaction mechanism and electronic interactions of SuPhenEx remain underexplored.

Purpose of the Study:

• To elucidate the electronic interactions governing SuPhenEx reactions at the molecular level.
• To investigate the influence of para-substituted phenolates and solvent effects on SuPhenEx reactivity.
• To provide insights for optimizing SuPhenEx and related S(VI) substitution reactions.

Main Methods:

• Density Functional Theory (DFT) calculations were employed.
• The Activation Strain Model was utilized to analyze reaction pathways.
• Model SuPhenEx reactions involving para-substituted phenolates and a nitrophenolate electrophile were studied in gas and solvent phases.

Main Results:

• The key electronic interaction determining reactivity in the gas phase is the HOMO-LUMO interaction.
• In the solvent phase (acetonitrile), reactivity is influenced by both HOMO-LUMO and (HOMO-1)-(LUMO+1) interactions.
• Reactivity can be effectively tuned by modifying the substituent on the phenolate nucleophile.

Conclusions:

• The study clarifies the electronic underpinnings of SuPhenEx reactions.
• Understanding these interactions allows for the rational design and steering of future SuPhenEx experiments.
• The findings contribute to the advancement of fluorine-free click chemistry methodologies.