Atroposelective PIII/PV=O Redox Catalysis for the Isoquinoline‐Forming Staudinger–aza‐Wittig Reaction

Herein, we describe the feasibility of atroposelective PIII/PV=O redox organocatalysis by the Staudinger–aza‐Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co‐catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N‐oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration. The atroposelective formation of isoquinoline heterocycles by a PIII/PV=O redox organocatalyzed Staudinger–aza‐Wittig reaction is described. With N2 release and aromatization as ideal driving forces, the method permits the synthesis of a broad range of atropisomeric isoquinolines under mild conditions with enantioselectivities of up to 98 : 2 e.r. and 93 % yield.