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

作者：Sun, Xiaohua; Li, Minxiong; Sun, Mingming; Li, Xiaobo; Xi, Brian J.; Wu, Yanjun; Yao, Jia; Zhan, Zeping; Bai, Xu; Xi, Ning^*

来源：Tetrahedron, 2018, 74(24): 2991-2998.

DOI：10.1016/j.tet.2018.04.090

• N-Phenyl gamma-lactams
• Atropisomerism
• Torsion angles
• Rotational barriers
• gamma-lactam conformations

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.

• 出版日期2018-6-14
• 单位吉林大学