Litcius/Paper detail

Atroposelective P<sup>III</sup>/P<sup>V</sup>=O Redox Catalysis for the Isoquinoline‐Forming Staudinger–aza‐Wittig Reaction

Daniel Moser, Kalipada Jana, Christof Sparr

2023Angewandte Chemie International Edition29 citationsDOIOpen Access PDF

Abstract

=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.

Topics & Concepts

IsoquinolineWittig reactionCatalysisChemistryRedoxMedicinal chemistryStereochemistryOrganic chemistryAxial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralityAsymmetric Synthesis and Catalysis