Effect of π-π interaction in Bergman cyclisation

Area of Science:

• Computational Chemistry
• Organic Reaction Mechanisms
• Supramolecular Chemistry

Background:

• Pi-pi interactions are crucial for molecular structure but their role in chemical reactivity is under-explored.
• Bergman cyclization, a key reaction in organic chemistry, provides a model system to study these interactions.
• Substrate flexibility influences how pi-pi interactions evolve during a reaction.

Purpose of the Study:

• To investigate the effect of pi-pi interactions on the activation barrier of the Bergman cyclization.
• To analyze how pi-pi interactions change along the reaction coordinate based on phenyl group flexibility.
• To determine the primary components of pi-pi interactions and their impact on reaction energetics.

Main Methods:

• Computational modeling of enediyne substrates with varying phenyl group linkers (0, 1, or 2 groups).
• Calculation of pi-pi interactions using multiple theoretical methods (BP86-D3BJ, B3LYP-D3BJ, M06-2X, SCS-MP2, SAPT).
• Energy decomposition analysis (SAPT) to quantify interaction components and geometric analysis to assess phenyl group orientation.

Main Results:

• Pi-pi interactions significantly influence Bergman cyclization activation energies, varying by up to 3.5 kcal mol(-1).
• Substrate flexibility dictates the evolution of pi-pi interactions, with less flexible substrates showing shorter minimum energy paths.
• Dispersive forces constitute the major attractive component (50-60%) of the pi-pi interactions.
• Electron-donating and withdrawing substituents enhance pi-pi interactions, stabilizing the transition state and increasing activation energy.

Conclusions:

• Pi-pi interactions play a critical role in modulating the reactivity and selectivity of the Bergman cyclization.
• The flexibility of phenyl groups is key to maintaining optimal pi-pi interactions throughout the reaction coordinate.
• Computational methods like BP86-D3BJ offer accurate predictions for pi-pi interaction energies in such systems.