Department of Chemistry and Biochemistry, San Diego State University, San Diego, California 92182-1030, United States.
J Org Chem. 2022 May 20;87(10):6760-6768. doi: 10.1021/acs.joc.2c00451. Epub 2022 Apr 29.
Diarylamines possess two potentially atropisomeric C-N axes; however, there are few examples of atropisomerically stable diarylamines in the literature, as the contiguous axes can allow for low energy racemization pathways via concerted bond rotations. Herein, we describe highly atropisomerically stable diarylamines that possess barriers to racemization of 30-36 kcal/mol, corresponding to half-lives to racemization on the decade to century time scale at room temperature. Investigation of the factors that led to the high stereochemical stability suggests that increased conjugation of the aniline lone pair of electrons into a more electron-deficient aryl ring, coupled with intramolecular hydrogen-bonding, locked the corresponding axis into a defined planar conformation, disfavoring the lower energy racemization pathways.
二芳基胺具有两个潜在的非对映异构 C-N 轴；然而，文献中很少有对映异构稳定的二芳基胺的例子，因为连续的轴可以通过协同键旋转允许低能量外消旋途径。在此，我们描述了高度对映异构稳定的二芳基胺，其外消旋化的能垒为 30-36kcal/mol，对应于室温下半衰期为十年到百年的外消旋化时间尺度。对导致高立体化学稳定性的因素的研究表明，苯胺孤对电子的共轭程度增加，进入更缺电子的芳环，加上分子内氢键，将相应的轴锁定在一个确定的平面构象中，不利于较低能量的外消旋化途径。
