Iridium‐Catalyzed Asymmetric Hydrogenation of 2, 3‐Diarylallyl Amines with a Threonine‐Derived P‐Stereogenic Ligand for the Synthesis of Tetrahydroquinolines and Tetrahydroisoquinolines. (31st May 2022)

• Record Type: Journal Article
• Authors: Rojo, Pep; Molinari, Medea; Cabré, Albert; García‐Mateos, Clara; Riera, Antoni; Verdaguer, Xavier
• Is Part Of: Angewandte Chemie. Volume 134:Number 29(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-31
• Subjects: Allyl Amines -- Asymmetric Hydrogenation -- Iridium -- P-Stereogenic -- Tetrahydroquinolines; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204300
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Chiral compounds containing nitrogen heteroatoms are fundamental substances for the chemical, pharmaceutical and agrochemical industries. However, the preparation of some of these interesting scaffolds is still underdeveloped. Herein we present the synthesis of a family of P‐stereogenic phosphinooxazoline iridium catalysts from L‐threonine methyl ester and their use in the asymmetric hydrogenation of N ‐Boc‐2, 3‐diarylallyl amines, achieving very high enantioselectivity. Furthermore, the synthetic utility of the 2, 3‐diarylpropyl amines obtained is demonstrated by their transformation to 3‐aryl‐tetrahydroquinolines and 4‐benzyl‐tetrahydroisoquinolines, which have not yet been obtained in an enantioselective manner by direct reduction of the corresponding aromatic heterocycles. This strategy allows the preparation of these types of alkaloids with the highest enantioselectivity reported up to date. Abstract : A P‐stereogenic phosphinooxazoline iridium catalyst prepared from L‐threonine methyl ester provides very high enantioselectivity in the asymmetric hydrogenation of N ‐Boc‐2, 3‐diarylallyl amines. The synthetic applicability of the resulting 2, 3‐diarylpropyl amines is demonstrated with the preparation of 3‐aryl‐tetrahydroquinolines and 4‐benzyl‐tetrahydroisoquinolines, achieving the highest ee values reported to date for this class of compounds.