Formal Total Synthesis of (−)-Isolaurallene and Structure Determination of (+)-4-epi-Isolaurallene via Stereodivergent Intramolecular Amide Enolate Alkylation

Abstract

Described herein are the formal total syntheses of (−)-isolaurallene (1) and structure determination of newly isolated (+)-4-epi-isolaurallene (2) via a highly stereodivergent intramolecular amide enolate alkylation (IAEA) strategy. Highly stereoselective constructions of α,α′-trans-THF 3 and α,α′-cis-THF 4 were accomplished by subjecting common intermediate 5 to non-chelate-controlled and chelate-controlled IAEA, respectively. The former protocol greatly improves the moderate stereoselectivity previously observed in constructing α,α′-trans-THF rings via intramolecular nitrile anion alkylation (INAA).