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

• Published in: Angewandte Chemie International Edition Vol. 59; no. 51; pp. 23077 - 23082
• Main Authors: Zhang, Lei, Shen, Jiahua, Wu, San, Zhong, Guofu, Wang, Yong‐Bin, Tan, Bin
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 14.12.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkynes; arylquinolines; atroposelectivity; axial chirality; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; chiral phosphoric acid; heteroannulation; Intermediates; Organic chemistry; Physical Sciences; Quinones; Science & Technology; Substrates; Thiourea; Vinylidene; BRONSTED ACID; arylquinolines; atroposelectivity; chiral phosphoric acid; ENANTIOSELECTIVE SYNTHESIS; 3-COMPONENT REACTION; ALKYLATION; AXIALLY CHIRAL COMPOUNDS; BIARYL COMPOUNDS; 2+2+2 CYCLOADDITION; PRIMARY ALCOHOLS; axial chirality; QUINOLINE; LIGANDS; heteroannulation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.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.