Synthesis of N,4-diaryl substituted ?-lactams via Kinugasa cycloaddition/rearrangement reaction

The methodology of construction of N,4-diaryl substituted [beta]-lactam framework, based on the Kinugasa cycloaddition/rearrangement sequence is presented. The series of protected chiral propargyl alcohols was treated with diaryl nitrones to afford mainly the cis-I adduct, providing direct access to...

Full description

Saved in:
Bibliographic Details
Published in:Tetrahedron 2012-12, Vol.68 (52), p.10806-10817
Main Authors: Michalak, Micha, Stodulski, Maciej, Stecko, Sebastian, Wonica, Magdalena, Staszewska-Krajewska, Olga, Kalicki, Przemysaw, Furman, Bartomiej, Frelek, Jadwiga, Chmielewski, Marek
Format: Article
Language:English
Subjects:
Adducts
Alcohols
Cycloaddition
Derivatives
Hydroxyl groups
Propargyl alcohol
Rings (mathematics)
Stereochemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The methodology of construction of N,4-diaryl substituted [beta]-lactam framework, based on the Kinugasa cycloaddition/rearrangement sequence is presented. The series of protected chiral propargyl alcohols was treated with diaryl nitrones to afford mainly the cis-I adduct, providing direct access to the highly-functionalized azetitidin-2-one derivatives with a well-defined stereochemistry. Under the optimized reaction conditions, the unprotected chiral propargylic alcohols were also found to be suitable precursors of [beta]-lactams. The absolute configuration of adducts was determined by CD or HPLC-CD technique, which was shown to be reliable method of determination of the configuration at C-4 of 4-aryl-substituted azetidin-2-ones. Epimerization of the cis adduct to the respective trans isomer could be easily done byANBthe oxidation of hydroxyl group next to the four-membered [beta]-lactam ring to the ketone, followed byANBaANBbase-mediated epimerization of the malonyl fragment.
ISSN:0040-4020
DOI:10.1016/j.tet.2011.11.007