ORGN 158 |
| When applied to coupling partners which have both single or multiple stereocenters as well as sensitive functionality, the Henry reaction proves to be a useful expedient due to the mildness of the reaction conditions and amenability to scale-up. A number of projects in our laboratory have involved the preparation of N, O-substituted 2-piperidinones with emphasis on both the relative stereochemistry of the nitrogen and oxygen substituents and the effective manipulation of their associated protecting groups. Although the piperidinone core can be found in many complex natural products and biologically active compounds, we have used it as an intermediate for the synthesis of biologically relevant substituted glutarimides. Conveniently-prepared N,N-di-BOC-substituted aspartate aldehydes are used as starting materials. The amino acid-derived aldehydes are treated with nitroalkanes under Henry conditions thereby affording the corresponding homologated nitroalkanols in good yield. Direct reduction of the nitroalkanols under mild conditions provided the corresponding (now BOC-protected-4-hydroxyornithine-derived) amino alcohols with concomitant cyclization to the corresponding substituted valerolactams. The protecting group chemistry of the N, O-substituted 2-piperidinones was explored and encompassed a variety of esterification, imidation and silylation reagents. Effective manipulation of the piperidinones along with their formation through reduction-cyclization will be presented in detail.
|
|
Heterocycles, Aromatics, Materials, Devices, Switches, Combinatorial Chemistry, Metal-Mediated Reactions
8:00 PM-10:00 PM, Sunday, 13 March 2005 Convention Center -- Hall D, Poster
Sci-Mix
Division of Organic Chemistry |