Convergent and Selective Synthesis of Pyrrolidinones, Piperidinones, Dihydropyridinones and Pyridinols from a Common Intermediate – Potential Precursors of Bioactive Products†

Titanium-mediated cyclopropanation of natural and unnatural β-amino acid derivatives provides azabicyclo[3.1.0]hexan-1-ols as mixtures of diastereomers that are separable by silica-gel chromatography. Depending on the ring cleavage procedure employed, these compounds lead efficiently to diverse intermediates for the synthesis of pharmaceuticals. Thus, depending on the experimental conditions, basic treatment can furnish racemic pyrrolidinones as a mixture of diastereomers and piperidinones. In contrast, the synthesis of optically active dihydropyridinones was achieved through a one-pot FeCl3/AcONa reaction or performed by using bis(sym-collidine)iodine hexafluorophosphate. Furthermore, whereas the palladium-mediated hydrogenolysis of these dihydropyridinones furnished both chiral piperidinones and original pyridinols, a CeIV-promoted radical process yielded chiral tricyclic piperidinones. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)