Higher-Order Electrocyclizations in Biological and Synthetic Processes.

Area of Science:

• Organic Chemistry
• Physical Chemistry
• Computational Chemistry

Background:

• Electrocyclizations typically adhere to Woodward-Hoffmann rules for up to eight π-electrons.
• Deviations from these rules are observed in higher-order electrocyclic reactions with increased π-electron systems.

Purpose of the Study:

• To review higher-order electrocyclizations involving 10, 12, 14, 16, and 18 π-electrons.
• To highlight the synthetic utility of these reactions for biologically active compounds.
• To elucidate reaction mechanisms using computational studies.

Main Methods:

• Literature review of reported higher-order electrocyclizations.
• Inclusion of Density Functional Theory (DFT) calculations for systems lacking prior computational analysis.
• Analysis of pericyclic topologies.

Main Results:

• Detailed examination of electrocyclizations involving 10 to 18 π-electrons.
• Identification of specific examples serving as intermediates in synthesizing bioactive molecules.
• Demonstration of DFT's role in explaining observed experimental selectivity.

Conclusions:

• Higher-order electrocyclizations present unique reactivity patterns beyond established Woodward-Hoffmann rules.
• Computational chemistry, particularly DFT, is crucial for understanding the mechanistic details and selectivity of these reactions.
• These reactions offer valuable pathways for constructing complex organic molecules.