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

Citation
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
Citations number
19
Categorie Soggetti
Chemistry & Analysis","Organic Chemistry/Polymer Science
Journal title
TETRAHEDRON
ISSN journal
00404020 → ACNP
Volume
55
Issue
47
Year of publication
1999
Pages
13321 - 13332
Database
ISI
SICI code
0040-4020(19991119)55:47<13321:SAONAN>2.0.ZU;2-R
Abstract
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.