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Versatile and concise routes to both racemic and chiral cyclopentane analogs of valinol are described. These compounds are constrained analogs of a key amino acid found in the aspartyl protease inhibitors of HIV-1.

By using a benzyl copper reagent (e.g. 10→11) in combination with titanium enolate chemistry (e.g. 12→13) a concise sequence has been developed for the rapid introduction of functionality found in the cytochalasin HIV protease inhibitor (1).

N-Aryl-mono-, -tri- and -pentacyclic pyridinium cations react with S- and C-nucleophiles to give: (i) simple addition of hydride at the α-ring position, (ii) nucleophilic addition of thiophenoxide at the γ-ring position, (iii) deprotonation at the 6-position of a 5,6-dihydroquinolinium ring followed by prototropic shift to give a 1,2-dihydroquinoline derivative, (iv) ring contraction of a pyridine to a pyrrole ring, and (v) nucleophilic displacement of the N-aryl group.