Asymmetric Synthesis of Multi-substituted beta-Lactams via C-N Axially Chiral Enolates in Intramolecular Conjugate Addition

作者：Yoshimura Tomoyuki^*

来源：Journal of the Pharmaceutical Society of Japan, 2012, 132(11): 1287-1295.

• beta-lactam
• amino acid
• axial chirality
• conjugate addition
• protonation
• reversibility

The synthesis of beta-lactams with contiguous tetra- and trisubstituted carbon centers has been accomplished via the 4-exo-trig intramolecular conjugate addition of C-N axially chiral enolates generated from alpha-amino acid derivatives. Use of a metal carbonate in a protic solvent (i.e., Cs2CO3 in EtOH) was found to be critical for the success of the reaction. Under optimized reaction conditions, axially chiral enolates were generated in very low concentration, thereby favoring intramolecular conjugate addition while minimizing intermolecular side reactions. The highly strained beta-lactam enolates formed through this reversible intramolecular conjugate addition were rapidly protonated by EtOH in the reaction media to afford beta-lactams in up to 97% ee.

• 出版日期2012-11