Remote Enantioselective Desymmetrization of 9,9-Disubstituted 9,10-Dihydroacridines through Asymmetric Aromatic Aminations
Dekun Zhang, Yingbo Shao, Wansen Xie, Yunrong Chen, Wei Liu, Hanyang Bao, Faqian He, Xiao‐Song Xue, Xiaoyu Yang
Abstract
Enantio-enriched 9,10-dihydroacridines are useful chiral N-heterocycles in many aspects; however, their asymmetric catalytic synthesis is rather challenging, as the stereocenter is remote to the functional group. Herein, we disclose an efficient remote enantioselective desymmetrization protocol through asymmetric aromatic aminations enabled by a new type of spirocyclic chiral phosphoric acid (CPA) catalyst, which gave access to a wide range of chiral dihydroacridines bearing 9,9-disubstitutions with extremely broad scope (compatible with both aryl,alkyl- and dialkyl-substitutions) and excellent enantioselectivities (up to >99% ee). In addition, this method was also applicable in the asymmetric construction of stereogenic silicon center and kinetic resolution of unsymmetrical dihydroacridine derivatives. Density functional theory calculations were performed to elucidate the origin of excellent regio- and enantioselectivity of these reactions, which arose from both the spirocyclic skeletons and the bulky polyaromatic substitutions of the CPA catalyst.