Abstract
Fenestranes, in which four rings share one carbon atom, have garnered much attention because of their flattened quaternary carbon centers. In addition, the rigid and nonplanar structures of heteroatom-containing fenestranes are attractive scaffolds for pharmaceutical applications. We report one-step syntheses of diaza-dioxa-fenestranes via the sequential (3 + 2) cycloadditions. Our synthesis employs readily synthesizable, nonbranched acyclic allenyl precursors that facilitate sequential cycloaddition reactions. We report the synthesis of 22 heteroatom-containing and differently substituted fenestranes with rings of varying sizes. The prepared diaza-dioxa-fenestranes are subjected to X-ray crystallography and DFT calculations, which suggest that replacing the carbon atoms at the non-bridgehead positions in the fenestrane skeleton with nitrogen and oxygen atoms results in a slight flattening of the quaternary carbon center. Moreover, one of our synthesized c,c-[5.5.5.5]fenestranes containing two isoxazoline rings possesses the flattest quaternary carbon center among previously synthesized heteroatom-containing fenestrane versions.