Autocatalysis in Eschenmoser Coupling Reactions

Area of Science:

• Organic Chemistry
• Reaction Mechanisms

Background:

• The Eschenmoser coupling reaction (ECR) is a vital synthetic method.
• Its mechanism, particularly the fate of thiirane intermediates, remains incompletely understood.
• Previous studies relied on external thiophiles, complicating mechanistic interpretation.

Purpose of the Study:

• To investigate the ECR mechanism in the absence of external thiophiles or bases.
• To identify the elusive intermediates responsible for product formation.
• To gain a comprehensive understanding of the ECR reaction pathway.

Main Methods:

• Electrospray ionization-mass spectrometry (ESI-MS) for intermediate detection.
• Ion mobility spectrometry and ion spectroscopy for structural characterization.
• Flow chemistry coupled with mass spectrometry for real-time reaction monitoring.

Main Results:

• Detection and characterization of polysulfide species (Sⁿ, n=2-16) as key intermediates.
• Observation of ECR proceeding without added thiophiles or bases.
• Identification of an autocatalytic pathway in the Eschenmoser coupling reaction.

Conclusions:

• Polysulfide species are crucial for ECR product formation.
• The ECR reaction exhibits autocatalysis, influencing its efficiency.
• This study provides novel mechanistic insights into the Eschenmoser coupling reaction.