The interconversion of benzene oxide and oxepin involves a thermally allowed 6-electron electrocyclic reaction. The nearly isoenergetic interconversion has a predicted barrier of 6 kcal/mol and has been observed by Sander and co-workers at cryogenic temperatures, indicating the process is dominated by heavy-atom tunneling. The biosynthesis of oxepin subunits in numerous natural products is proposed to arise via benzene oxide intermediates. As part of an effort to explore heavy-atom tunneling in biosynthesis (to date, not detected experimentally), we report computational results on the interconversion of benzene oxide and oxepin, as well as related reactions in previously proposed biosynthetic pathways. For the conversion of benzene oxide to oxepin, M06-2X/6-31G* computed rate constants with and without multidimensional tunneling contributions yield a tunneling-inclusive rate constant of 4.6 x 10-5 s-1 at 60 K (vs. 1.1 x 10-11 s-1 without tunneling) and a &gt;99.9% contribution of tunneling to the rate. Preliminary calculations on conversion of benzene oxide moieties to oxepin subunits in the natural products oxepinamide and dehydroperilloxin yield exothermicities of &gt;10 kcal/mol and barriers of less than 2 kcal/mol, suggesting these processes most likely proceed by over-barrier paths rather than tunneling.

Computational study of heavy-atom tunneling in the benzene-oxide/oxepin equilibrium

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.