Alkyl radical cyclization to vinylogous carbonates for the stereoselective synthesis of unsymmetrical dioxa-cage compounds: effect of conformation on the rate of cyclization versus reduction

An efficient strategy for the stereoselective construction of unsymmetrical dioxa-cage compounds containing ether linkages employing a 6-exo-trig alkyl radical cyclization to vinylogous carbonates is developed. The radical precursors are prepared from the diols obtained from the Diels–Alder adducts via iodoetherification followed by addition of the alcohol to the ethyl propiolate. The geometrical constrains play important role in deciding the outcome of the reaction as cyclization versus simple reduction. Formation of the mono-oxa-cage compounds via a 5-exo-trig intramolecular alkyl radical cyclization to olefin is also described. The dioxa-cages could also be assembled employing a tandem oxymercuration reduction-radical cyclization to vinylogous carbonates protocol with equal efficiency and with reduced number of steps.

Graphical abstractDioxa-cage compounds are prepared by radical cyclization to the vinylogous carbonates in a highly stereoselective manner. The formation of monooxa-cage compounds via a 5-exo-trig intramolecular alkyl radical cyclization to olefin is also described. Geometrical constrains play an important role in dictating the outcome of these reactions (cyclization vs simple reduction).Figure optionsDownload full-size imageDownload as PowerPoint slide