Sequential radical cyclization approach to propellane triquinanes. Total synthesis of (±)-modhephene

Article abstract of DOI:10.1021/ja00170a025

Modhephene (1) was synthesized in >21% yield from the α,β-unsaturated β-stannyl enoate 24. The key steps were the radical addition-fragmentation reaction of vinylstannane 25, which was endo stereoselective and occurred in 90% yield, and the radical cyclization of the iodovinyl ketone 52, which occurred in 88% yield. The high stereoselectivity in the cyclization of 25 is due in part to the Me₃Sn substituent; the destannylated analogue 29 cyclized to give a 3:1 endo/exo mixture. The radical cyclization of bromoalkene 16 gave desmethylmodhephene (19), while the cyclization of bromoalkene 36 gave propellane 37, which was nonselectively converted to modhephene (1) and isomodhephene (39) by Reetz dimethylation. The radical cyclization of cyclopentenyl bromide 8 gave a 5:1 mixture of stereoisomers 10 but only a 3:1 mixture of cyclized (10)/uncyclized (11) isomers. A new retrosynthetic notation for use in synthetic planning with radical reactions is also described.