Construction of Pentacyclic Limonoid Skeletons via Radical Cascade Reactions

Limonoids 1 and 2 share a 6/6/6/5-membered ABCD-ring system and a six-membered oxacycle and differ in their C9-stereochemistries. A new radical-based strategy was devised to construct the pentacyclic skeletons of 1 and 2. An oxacycle-fused A-ring and enyne fragments were coupled to produce radical precursors 4a-4c with different C7-oxygen functionalities. The bridgehead tertiary bromide of 4a-4c participated in a radical cascade reaction with the three unsaturated bonds to cyclize the C9-diastereomeric BCD-rings.

Automated summary

Limonoids 1 and 2 share a 6/6/6/5-membered ABCD ring system and a six-membered oxacycle, but differ in their C9-stereochemistries. A novel radical-based strategy was developed to construct the pentacyclic skeletons of 1 and 2, by coupling oxacycle-fused A-ring and enyne fragments to produce radical precursors 4a-4c with different C7-oxygen functionalities, which then participated in a radical cascade reaction to cyclize the C9-diastereomeric BCD rings.