Studies on structural requirements for atropisomerism in N-phenyl gamma-lactams

We prepared a series of substituted N-phenyl gamma-lactams to investigate the structural requirements for forming atropisomers. NMR spectroscopic and X-ray crystallographic data as well as chiral HPLC analyses proved that ortho-F, Cl-disubstituted N-phenyl gamma-lactams (i.e., RS-4 and SS-4) yielded separable atropisomers. Computational studies using the conformational data derived from crystal structures showed that conformational variations in the gamma-lactam ring had negligible impacts on the rotational barriers of the N-phenyl group around the central C-N bond. Atropisomerism in N-phenyl gamma-lactams was depended solely on the steric interactions between bulky ortho-substituents on the N-phenyl group and the adjacent CH2 and C=O groups in the gamma-lactam. (C) 2018 Elsevier Ltd. All rights reserved.