Stereospecific synthesis of 2-substituted bicyclic thiazolidine lactams

Bicyclic thiazolidine lactam 1 was used as a model system for developing synthetic methodology into β-turn mimics that would contain side chain functionality. Treatment of a mixture of 1 and a non-enolizable aldehyde at -100°C with LDA resulted in a good yield of the aldol adduct when aromatic aldehydes were used. Radical dehydroxylation of the pentafluorophenylcarbonate derivative of the aldol adduct with (n-Bu)₃SnH and AIBN gave a single isomer of the C-2 alkylated bicyclic 5,5-thiazolidine lactam. This methodology was applied to the synthesis of the 2-substituted spiro bicyclic thiazolidine lactam type II' β-turn mimic 14.