Enantioselective Synthesis of Planar-Chiral Macrocycles through Asymmetric Electrophilic Aromatic Amination

Donglei Wang; Ying-Bo Shao; Yunrong Chen; Xiao-Song Xue; Xiaoyu Yang

doi:10.1002/anie.202201064

Enantioselective Synthesis of Planar-Chiral Macrocycles through Asymmetric Electrophilic Aromatic Amination

Angew Chem Int Ed Engl. 2022 May 23;61(22):e202201064. doi: 10.1002/anie.202201064. Epub 2022 Mar 30.

Authors

Donglei Wang¹, Ying-Bo Shao², Yunrong Chen¹, Xiao-Song Xue^{3

4}, Xiaoyu Yang¹

Affiliations

¹ School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, P. R. China.
² College of Chemistry, Nankai University, Tianjin, 300071, P. R. China.
³ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
⁴ School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, 310024, China.

PMID: 35293123
DOI: 10.1002/anie.202201064

Abstract

An efficient approach for asymmetric synthesis of planar-chiral macrocycles (paracyclophanes) has been disclosed through enantioselective electrophilic aromatic aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. A wide range of chiral macrocycles bearing varied ring sizes (16 to 23-membered) and functional group-containing ansa chains were readily afforded using this method, with excellent yields and high enantioselectivities (23 examples, up to 99.5 : 0.5 er). Experimental studies and DFT calculations were performed to elucidate the mechanism and origin of stereoselectivities of these reactions. Preliminary utilization of the planar-chiral macrocycle as chiral organocatalyst showcased the potential applications of these novel chiral skeletons.

Keywords: Amination; Asymmetric Catalysis; Macrocycles; Organocatalysis; Paracyclophanes.

Abstract

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