Stereocontrolled Synthesis of 4-6-Ring Lactams

Significance

A previous report has shown that 3-(methoxyphenyl)propiohydroxamates undergo stereoselective nitrenium ion mediated spirocyclization upon treatment with phenyliodine(III)bis(trifluoroacetate) to give spirolactams with moderate to high diastereoselectivity and in modest to excellent yields (D. J. Wardrop et al. Tetrahedron Lett . 2003, 44, 2587-2591). The current paper demonstrates that ozonolysis of the spiro derivatives yields azetidinones, pyrrolidinones and piperidinones bearing quaternary carbon stereocenters. The somewhat unstable aldehydes may be converted in situ into stable derivatives, e.g., aldoximes, hydrazones, 1,2-dithiolanes, β-hydroxyesters (27-88% yields over 2 steps). The N-protecting group may be cleaved in good yield using molybdenumhexacarbonyl in presence of air (R¹ = OMe) and catalytic hydrogenation (R¹ = Bn).