Cneorins, cyclopropanes and propellanes: Synthesis of windmill molecules

Abstract

Propellanes are molecules in which a tricyclic system is conjoined by a carbon–carbon single bond. They have been studied both theoretically and synthetically. Propellane structures are present in many different classes of natural products. Total syntheses of these natural products are reviewed.

Cneorin C has been isolated from the xerophytic shrub Cneorum pulverulentum, which is native to the Canary Islands. It is a natural product containing a [4.3.1]propellane ring system as the northern part of the molecule and a 5,5-spiroketal unit and a butenolide moiety as the southern part. Despite the intriguing structure, the molecule has not attracted synthetic attention except from our group. The northern DEFG ring system of cneorin C is an ideal candidate for the copper-catalyzed intramolecular cyclopropanation of a diazomalonate. The synthesis of the DEFG ring system of cneorin C is described. The key steps include: 1) an enzymatic kinetic resolution providing the first stereogenic center of the molecule in an enantioselective fashion, 2) intramolecular cyclopropanation of a diazomalonate providing the EFG ring fragment and 3) an anionic cyclization of a sulfone yielding the [4.3.1]propellane ring system.