Conformational Isomerization as a Process to Determine Selectivity over Reaction Pathways: Effect of Alkene Rotation...

Area of Science:

• Organic Chemistry
• Organometallic Chemistry
• Computational Chemistry

Background:

• Bond-forming and bond-cleaving reactions are typically key in organic synthesis.
• Conformational isomerization is often overlooked as a selectivity-determining factor.
• Palladium-catalyzed alkyl isomerization, or chain walking, is a significant synthetic tool.

Purpose of the Study:

• To investigate the role of conformational isomerization in determining selectivity in palladium-catalyzed chain walking reactions.
• To identify the rate-determining step in alkylpalladium isomerization.
• To elucidate the mechanism of palladium chain walking, particularly concerning alkene intermediates.

Main Methods:

• Theoretical calculations (e.g., density functional theory) to model reaction pathways and transition states.
• Experimental studies to validate theoretical predictions and observe reaction outcomes.
• Analysis of energy barriers for various steps including alkene rotation, beta-hydride elimination, and migratory insertion.

Main Results:

• Alkene rotation was identified as the highest energy barrier transition state in some alkylpalladium isomerization events.
• Transition states for beta-hydride elimination and migratory insertion were not observed computationally.
• Both theoretical and experimental evidence suggests palladium chain walking favors cis alkene intermediates over trans alkene intermediates due to rotational barriers.

Conclusions:

• Conformational isomerization, specifically propeller-like alkene rotation, can be the selectivity-determining step in organic reactions.
• The mechanism of palladium chain walking involves cis alkene intermediates due to the energetic cost of alkene rotation.
• This finding challenges the traditional view of bond-forming/cleaving processes as solely dominant in reaction selectivity.