Free-radical carbo-oximation of olefins and subsequent radical-ionic cascades

A sequential carbo-formylation cascade has been developed, involving a free-radical carbo-oximation process, followed by the hydrolysis of the oxime ether. For this purpose, we designed a new SEM O-protected sulfonyl oxime, which enable both rapid radical addition and hydrolysis under mild conditions. The resulting aldehyde-esters were then engaged in various nucleophilic cascades, such as Sakurai allylations or domino-Mukaiyama aldol condensation/lactonizations. Addition of an amine and TMSCN similarly led after Strecker reaction/lactamization to α-cyano-piperidinones in good overall yield. Finally, a Pictet-Spengler/lactamization sequence was devised, which open a new entry toward the tricyclic core of eburnan alkaloids.

Graphical abstractDownload full-size image