Design and Atroposelective Construction of IAN analogues by Organocatalytic Asymmetric Heteroannulation of Alkynes

• Published in: Angewandte Chemie Vol. 132; no. 51; pp. 23277 - 23282
• Main Authors: Zhang, Lei, Shen, Jiahua, Wu, San, Zhong, Guofu, Wang, Yong‐Bin, Tan, Bin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 14.12.2020
• Subjects: Alkynes; arylquinolines; atroposelectivity; axial chirality; Chemical reactions; Chemistry; chiral phosphoric acid; heteroannulation; Intermediates; Organic chemistry; Quinones; Substrates; Thiourea; Vinylidene
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202010598

An organocatalytic atroposelective strategy for accessing enantioenriched axially chiral IAN analogues was developed for the first time. A class of novel atropisomeric C2‐arylquinoline skeletons were synthesized with high enantiocontrol via chiral phosphoric‐acid‐catalyzed heteroannulation of in situ generated vinylidene ortho‐quinone methide (VQM) intermediates with ortho‐aminophenones. The strategy tolerated a broad substrate scope, providing a facile organocatalytic approach to IAN analogues in good yields and excellent enantioselectivities under mild reaction conditions. Moreover, the synthetic utility of this methodology was illustrated through further transformations into IAN‐type ligand and axially chiral thiourea. An organocatalytic strategy for accessing enantioenriched axially chiral IAN analogues has been developed. A class of novel atropisomeric C2‐arylquinoline skeletons were synthesized with high enantiocontrol via chiral phosphoric acid catalyzed heteroannulation of alkynes. The synthetic utility was shown by further transformations into IAN‐type ligand and axially chiral thiourea.