THE ASYMMETRIC-SYNTHESIS OF FUSED CYCLOPENTENONE RING-SYSTEMS - A FORMAL ASYMMETRIC TOTAL SYNTHESIS OF (-)-ISOCOMENE

Optically active tricyclic oxazolidine lactams 10 have been prepared u sing two different routes (Scheme 1). They can be obtained by acid-med iated intramolecular cyclization of bicyclic lactams 13 via their acyl iminium intermediates producing appended five-, six-, and seven-member ed tricyclic systems. Alternatively, 10 can be prepared by cycloconden sation of chiral amino alcohols with cyclopmtane-1,2-dicarboxylic acid s 12 to give the imide which is reduced or alkylated to the amino alco hols and cyclized to a diastereoisomer mixture of 10. Alkylation of 10 (R'' = H) via its enolate gives stereospecifically alpha-quaternary p roducts 10 (R'' = alkyl). Degradation of the latter with MeLi or Red-A l(R) followed by mild acid hydrolysis and aldol cyclization produces t he bicyclic ketones 14 and 15 as 1:1 mixtures, readily separated and i solated in > 99% ee. This sequence produced a known non-racemic interm ediate 69 for the synthesis of (-)-isocomene.