Addition of Highly Polarized Organometallic Compounds to N‐tert‐Butanesulfinyl Imines in Deep Eutectic Solvents under Air: Preparation of Chiral Amines of Pharmaceutical Interest. Issue 14 (29th June 2020)

• Record Type: Journal Article
• Authors: Cicco, Luciana; Salomone, Antonio; Vitale, Paola; Ríos‐Lombardía, Nicolás; González‐Sabín, Javier; García‐Álvarez, Joaquín; Perna, Filippo M.; Capriati, Vito
• Is Part Of: ChemSusChem. Volume 13:Issue 14(2020)
• Page Start: 3583
• Page End: 3588
• Publication Date: 2020-06-29
• Subjects: amines -- deep eutectic solvents -- Grignard reagents -- imines -- organolithium reagents; Green chemistry -- Periodicals; Sustainable engineering -- Periodicals; Chemistry -- Periodicals; Chemical engineering -- Periodicals; 660
• DOI: 10.1002/cssc.202001142
• Languages: English
• ISSNs: 1864-5631

Abstract

Abstract: Highly polarized organometallic compounds of s‐block elements are added smoothly to chiral N‐tert ‐butanesulfinyl imines in the biodegradable d ‐sorbitol/choline chloride eutectic mixture, thereby granting access to enantioenriched primary amines after quantitatively removing the sulfinyl group. The practicality of the method is further highlighted by proceeding at ambient temperature and under air, with very short reaction times (2 min), enabling the preparation of diastereoisomeric sulfinamides in very good yields (74–98 %) and with a broad substrate scope, and the possibility of scaling up the process. The method is demonstrated in the asymmetric syntheses of both the chiral amine side‐chain of ( R, R )‐Formoterol (96 % ee ) and the pharmaceutically relevant ( R )‐Cinacalcet (98 % ee ). Abstract : Embraced by nature : Highly enantioenriched amines, which are key intermediates in the synthesis of valuable APIs, are obtained by the fast and chemoselective addition of organolithium or Grignard reagents to chiral sulfinyl imines, under hydrous conditions and at ambient temperature, in the biodegradable d ‐sorbitol/choline chloride eutectic mixture.