Chiral Ligand‐Mediated Nucleophilic Aromatic Substitution of Naphthoic Acids: A Fast and Efficient Access to Axially Chiral Biaryls

• Published in: European journal of organic chemistry Vol. 2020; no. 25; pp. 3829 - 3833
• Main Authors: Nguyen, Thi Thanh Thuy, Guyon, Hélène, Nguyen, Kim Phi Phung, Boussonnière, Anne, Mortier, Jacques, Castanet, Anne‐Sophie
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 07.07.2020; Wiley-VCH Verlag
• Subjects: Axial chirality; Biaryls; Chemical Sciences; Chiral ligands; Diamines; Ligands; Nucleophilic aromatic substitution; Organic chemistry; Organolithium compounds; Substitution reactions; Transition metals; Organolithium compounds; Nucleophilic aromatic substitution; Biaryls; Chiral ligands; Axial chirality
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202000317

A transition metal‐free synthesis of enantioenriched biaryls from aryllithium species has been developed. This approach relies on atropoenantioselective nucleophilic aromatic substitution (SNAr) reaction of unprotected naphthoic acids. The ability of a diverse set of chiral ligands to mediate this transformation has been investigated. 1,2‐diether ligands outperform their diamine counterparts and the best enantiocontrol was obtained with readily accessible enantiopure trans‐1,2‐dimethoxycyclohexane. This SNAr reaction offers an efficient and rapid access to enantioenriched binaphthalenes, phenylnaphthalene, and phenanthrylnaphthalenes (up to 94:6 er). A transition metal‐free synthesis of enantioenriched biaryls through nucleophilic aromatic substitution (SNAr) reaction of naphthoic acids is reported. The best enantiocontrol was obtained with enantiopure trans‐1,2‐dimethoxycyclohexane. This reaction offers an efficient access to enantioenriched binaphthalenes, phenylnaphthalenes, and phenanthrylnaphthalenes.