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

Thi Thanh Thuy Nguyen (1) , Hélène Guyon (1) , Kim Phi Phung Nguyen (2) , Anne Boussonniere (1) , Jacques Mortier (1) , Anne-Sophie Castanet (1)

1 IMMM - Institut des Molécules et Matériaux du Mans
2 VNU-HCM - Vietnam National University, Ho Chi Minh City / Đại học Quốc gia TP. Hồ Chí Minh

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).

Mots clés: Axial chirality; Biaryls; Chiral ligands; Nucleophilic aromatic substitution; Organolithium compounds

Domaines: Chimie organique

Thi Thanh Thuy Nguyen, Hélène Guyon, Kim Phi Phung Nguyen, Anne Boussonniere, Jacques Mortier, et al.. Chiral Ligand-Mediated Nucleophilic Aromatic Substitution of Naphthoic Acids: A Fast and Efficient Access to Axially Chiral Biaryls. European Journal of Organic Chemistry, 2020, 2020 (25), pp.3829-3833. ⟨10.1002/ejoc.202000317⟩. ⟨hal-02901683⟩