Novel 3, 4-dihydro-1, 4-oxazine (dehydromorpholine) sulfonamides and sulfones conveniently accessed from suitable a-diazoketones via OH carbene insertion – Cyclization sequence. (17th August 2021)

• Record Type: Journal Article
• Authors: Solovyev, Igor; Dar'in, Dmitry; Krasavin, Mikhail
• Is Part Of: Tetrahedron letters. Volume 78(2021)
• Publication Date: 2021-08-17
• Subjects: Alpha-Acyl-alpha-diazomethane sufones and solfamides -- Rh(II) carbene O-H insertion -- Tandem SN2 – enamine formation -- Dehydromorpholines -- Privileged structures; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2021.153269
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Morpholines with novel substitution patterns are sought after in drug design. α-Acyl-α-diazomethane sulfon(amid)es are ameanable by the SAFE method. These have been coupled with 2-bromoethanol via Rh(II)-catalyzed reaction. The intermediates were transformed into dehydromorpholines. The process involves tandem S N 2/enamine formation (in this or reverse order). Abstract: A short and practically convenient, modular approach to hitherto unknown dehydromorpholine sulfones and sulfonamides from α-acyl-α-diazomethyl sulfones and sulfonamides, respectively, has been developed. It involves Rh(II) carbene insertion into the OH bond of 2-bromoethanol followed by thermally promoted tandem S N 2 displacement of the bromine atom by a primary amine and cyclodehydration.