Spirocyclizations Involving Oxonium Ylides Derived from Cyclic α-Diazocarbonyl Compounds: An Entry into 6-Oxa-2-azaspiro[4.5]decane Scaffold

Abstract

New types of cyclic diazo compounds capable of Rh(II)-catalyzed spirocyclizations with tetrahydrofuran have been discovered. The formation of the spirocyclic framework is thought to proceed <i>via</i> the formation of Rh(II) carbene species followed by interaction with the Lewis basic oxygen atom of tetrahydrofuran to give oxonium ylide species. The latter evolves predominantly <i>via</i> the Stevens type rearrangement leading to an [<i>n</i> + 1] ring expansion of the tetrahydrofuran moiety, which results in the formation of a medicinally relevant 6-oxa-2-azaspiro[4.5]decane scaffold. The spirocyclization process was often observed in competition with mechanistically distinct C-H insertion into a tetrahydrofuran molecule. This competing process gave compounds based on the 3-(tetrahydrofur-2-yl)pyrrolidine scaffold, which are also relevant from the medicinal chemistry standpoint. These findings enrich the available arsenal of metal-catalyzed spirocyclization methods based on the use of cyclic diazo compounds.