Typical methods for the conjugate reduction of alpha-beta unsaturated compounds involve the use of hydrogen gas and expensive metal catalysts, or hydride transfer reagents that are not atom-economical. Recently, methodologies based on radical hydrogen atom transfer (HAT) have become popular, though there is still need for a metal catalyst in these processes. Interestingly, there are no reported examples in the literature of an uncatalyzed (at least not by transition metals) reduction of a conjugated substrate through a non-radical HAT process. We report the first examples of such a process, which was discovered serendipitously while attempting a simple thermal solvolysis of an alkylidene, derived from Meldrum's acid, in isopropanol. The C=C double bond was reduced, presumably through a concerted HAT process, and the ring was opened to provide a desymmetrized malonate half ester. It was also found that catalytic amounts of readily available boronic acids were capable of both improving the conversion and isolated yield in this HAT process.<br/>Besides isopropanol, a handful of other secondary alcohols were found to reduce the alpha-beta unsaturated substrates. Currently only aldehyde-derived alkylidenes undergo this reduction, while ketone-derived alkylidenes of Meldrum’s acid only undergo solvolysis. This difference in reactivity can be exploited for the purpose of chemoselectivity. The mechanism is being investigated both experimentally and computationally.

Tandem 1,4-reduction/solvolysis of Meldrum’s acid-derived alkylidenes in isopropanol catalyzed by boronic acids

ACS Spring 2022

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