Theoretical Insight into Stereoselective Reaction Mechanisms of 2,4-Pentanediol-Tethered Ketene-Olefin [2 + 2] Cycloaddition

We report ab initio molecular dynamics calculations based
on density
functional theory performed on an intramolecular [2 + 2] cycloaddition
between ketene and olefin linked with a 2,4-pentanediol (PD) tether.
We find that the encounter of the ketene and olefin moieties could
be prearranged in the thermal equilibrated state before the cycloaddition.
The reaction mechanism is found to be stepwise, similar to that of
intermolecular ketene [2 + 2] cycloadditions with ordinary alkenes.
A distinct feature of the reaction pathway for a major diastereoisomer
is a differential activation free energy of about 1.5 kcal/mol, including
2.8 kcal/mol as the differential activation entropy, with a transition
state consisting of a flexible nine-membered ring in the olefin-PD-ketene
moiety. This theoretical study provides a reasonable explanation for
the strict stereocontrollability of the PD-tethered ketene-olefin
cycloaddition, irrespective of reaction types or conditions.