Quaternary Ammonium Ion-Tethered (Ambient-Temperature) HDDA Reactions

The hexadehydro-Diels–Alder
(HDDA) reaction converts a 1,3-diyne
bearing a tethered alkyne (the diynophile) into bicyclic benzyne intermediates
upon thermal activation. With only a few exceptions, this unimolecular
cycloisomerization requires, depending on the nature of the atoms
connecting the diyne and diynophile, reaction temperatures of ca. 80–130 °C to achieve a convenient half-life
(e.g., 1–10 h) for the reaction. In this report,
we divulge a new variant of the HDDA process in which the tether contains
a central, quaternized nitrogen atom. This construct significantly
lowers the activation barrier for the HDDA cycloisomerization to the
benzyne. Moreover, many of the ammonium ion-based, alkyne-containing
substrates can be spontaneously assembled, cyclized to benzyne, and
trapped in a single-vessel, ambient-temperature operation. DFT calculations
provide insights into the origin of the enhanced rate of benzyne formation.