Thomas Lindel and co-workers at TU Braunschweig have recently published in Organic Letters on the enantioselective synthesis of a cubitane carbon skeleton that is a 12-membered macrocycle. The method they used was the radical cyclization approach. There is a carbon carbon bond cleavage involved that requires the introduction of an alpha-hydroperoxy group on a ketone followed by an alkyl shift, which leads to the generation of an oxacarbenium ion that gets hydrolyzed to yield the 12-membered macrocycle. The alpha-hydroperoxy ketone intermediate is generated by treating the ketone with lithium aluminum hydride in ether for 2 days under air exposure.
Archive for the ‘Cubitane’ Category