Novel extension of Meyers' methodology: stereoselective construction of axially chiral 7,5-fused bicyclic lactams

J Org Chem. 2003 Nov 28;68(24):9517-20. doi: 10.1021/jo035195i.

Abstract

A novel extension of Meyer's lactamization is reported for the preparation of seven-membered ring lactams 1a-d incorporating a biaryl unit. The required keto-esters 2a-c were readily accessible via the Suzuki coupling reaction. A borylation-Suzuki coupling (BSC) sequence was successfully developed for the high-yielding preparation of keto-ester 2d. Cyclization of the resulting keto-esters 2a-d or keto-acids 5a,c,d in the presence of (R)-phenylglycinol afforded the desired lactams 1a-d in high yields (72-93%) and excellent diastereoselectivities (>95%). This methodology provides a facile stereoselective access to new axially chiral bridged biaryls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques / methods*
  • Cyclization
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Ligands
  • Models, Chemical
  • Molecular Structure
  • Stereoisomerism
  • Time Factors

Substances

  • Lactams
  • Ligands