The Asymmetric Synthesis of Fused Cyclopentenone Ring Systems: A formal asymmetric total synthesis of (−)‐isocomene

Abstract

AbstractOptically active tricyclic oxazolidine lactams 10 have been prepared using two different routes (Scheme 1). They can be obtained by acid‐mediated intramolecular cyclization of bicyclic lactams 13 via their acyliminium intermediates producing appended five‐, six‐, and seven‐membered tricyclic systems. Alternatively, 10 can be prepared by cyclocondensation of chiral amino alcohols with cyclopentane‐1,2‐dicarboxylic acids 12 to give the imide which is reduced or alkylated to the amino alcohols and cyclized to a diastereoisomer mixture of 10. Alkylation of 10 (R″ = H) via its enolate gives stereospecifically α‐quaternary products 10 (R″ = alkyl). Degradation of the latter with MeLi or Red‐Al® followed by mild acid hydrolysis and aldol cyclization produces the bicyclic ketones 14 and 15 as 1:1 mixtures, readily separated and isolated in > 99% ee. This sequence produced a known non‐racemic intermediate 69 for the synthesis of (−)‐isocomene.