Stereoselective alkylation of N-Boc-2-pyrrolidinones and N-Boc-2- piperidinones. Synthesis and characterization of disubstituted lactams

Article abstract of DOI:10.1016/S0040-4020(99)00835-2

Alkylation of enolates of monosubstituted N-Boc lactams 4-6 afforded trans-disubstituted lactams as the major isomer. In the pyrrolidinone series, 1,3-induction seems to be ruled by steric interactions and the diastereoselection is low for the alkylation of enolates with small substituents at C-5 (e.g., Me) and methyl iodide. The trans selectivity improves with bulkier substituents at C-2 and/or bulkier electrophiles. The formation of 3,6-trans-disubstituted piperidinones benefits from the axial orientation of the substituent at C-2 due to the A strain with the N-Boc group and excellent trans preference is observed even in the alkylation of the lithium enolate of N-Boc-6-methyl piperidinone with methyl iodide.