Troponoid Atropisomerism: Studies on the Configurational Stability of Tropone-Amide Chiral Axes

• DOI: 10.1021/acs.orglett.9b00707
• Publication Date: 2019-03-14T14:28:13Z
• Authors: Danielle R. Hirsch; Anthony J. Metrano; Elizabeth A. Stone; Golo Storch; Scott J. Miller; Ryan P. Murelli
• Keywords: Tropone; Atropisomer; Amide

Configurationally stable, atropisomeric motifs are an important structural element in a number of molecules, including chiral ligands, catalysts, and molecular devices. Thus, understanding features that stabilize axes is fundamental interest throughout the chemical sciences. The following details high rotational barriers about Ar–C(O) bond tropone amides, which significantly exceed those analogous benzamides. These studies supported by both experimental computational barrier measurements. We also report resolution axially α-hydroxytropolone amide into its individual atropisomers, demonstrate configurational stability at physiological pH temperatures over 24 h.