Thermal C1-C5 diradical cyclization of enediynes

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Reaction Mechanisms

Background:

• The Bergman cyclization is a key reaction for 1,5-diynes.
• Aryl-substituted 1,2-diethynylbenzenes present unique electronic and steric environments.

Purpose of the Study:

• To investigate the competition between C1-C5 and C1-C6 cyclization pathways in aryl-substituted 1,2-diethynylbenzenes.
• To elucidate the mechanisms governing the thermolysis of these compounds.

Main Methods:

• Density Functional Theory (DFT) calculations using BLYP/6-31G(d) and BCCD(T)/cc-pVDZ levels.
• Experimental thermolysis of 1,2-bis(2,4,6-trichlorophenylethynyl)benzene and 1,2-bis(phenylethynyl)benzene.
• Deuterium labeling studies and thermolysis in the absence of 1,4-cyclohexadiene.

Main Results:

• Computational studies predict that steric effects disfavor C1-C6 (Bergman) cyclization, while electronic effects favor C1-C5 cyclization.
• Thermolysis of 1,2-bis(2,4,6-trichlorophenylethynyl)benzene exclusively yields C1-C5 cyclization products.
• C1-C5 cyclization products are competitive with the Bergman reaction for the parent 1,2-bis(phenylethynyl)benzene.
• Direct C1-C5 diradical cyclizations were confirmed experimentally.

Conclusions:

• Electronic factors significantly influence the cyclization pathways in aryl-substituted 1,2-diethynylbenzenes.
• The C1-C5 cyclization pathway is a crucial reaction mechanism in the thermolysis of these systems.
• This study highlights the importance of considering electronic effects in predicting reaction outcomes for enediynes.