Samarium(II)-mediated 4-exo-trig cyclization. A stereocontrolled approach to the core of pestalotiopsin A.

[reaction: see text] Pestalotiopsin A is a structurally unique caryophyllene-type sesquiterpene which has shown immunosuppressive activity and cytotoxicity in preliminary assays. A stereocontrolled approach to the functionalized 2-oxabicyclo[3.2.0]heptane core of pestalotiopsin A is described. The approach includes a samarium(II)-mediated 4-exo-trig cyclization and a trans-lactonization process triggered by the addition of alkylytterbium reagents to a cyclobutanone intermediate.