Intramolecular Cyclization Manifolds of 4‑Alkylpyridines Bearing Ambiphilic Side Chains: Construction of Spirodihydropyridines or Benzylic Cyclization via Anhydrobase Intermediates

4-Alkylpyridines possessing nucleophilic β-dicarbonyl
side
chains have been converted to spirodihydropyridines upon treatment
with ethyl chloroformate and sub-stoichiometric amounts of Ti­(OiPr)4. Alternatively, inclusion
of mild base in the reaction medium was found to facilitate generation
of anhydrobase intermediates. Subsequent aldol-like condensations
with electrophilic side chain moieties followed by hydrolysis delivered
benzylically cyclized pyridines in good yield. In situ hydrogenation
of cyclized anhydrobase intermediates afforded 4-substituted piperidines.