Ao. Maldaner et Ra. Pilli, Stereoselective alkylation of N-Boc-2-pyrrolidinones and N-Boc-2-piperidinones. Synthesis and characterization of disubstituted lactams, TETRAHEDRON, 55(47), 1999, pp. 13321-13332
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 diastereoselect
ion 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 sub
stituents at C-2 and/or bulkier electrophiles. The formation of 3,6-trans-d
isubstituted piperidinones benefits from the axial orientation of the subst
ituent at C-2 due to the A(1,3) strain with the N-Boc group and excellent t
rans preference is observed even in the alkylation of the lithium enolate o
f N-Boc-6-methyl piperidinone with methyl iodide. (C) 1999 Elsevier Science
ltd. All rights reserved.