Reduction of 2-hydroxy-3-arylmorpholines to 3-aryl morpholines. Issue 25 (19th June 2020)

• Record Type: Journal Article
• Authors: Wright, Stephen W.; Simpson, Brittany; Chinigo, Gary; Perry, Matthew A.; Maguire, Robert J.
• Is Part Of: Tetrahedron. Volume 76:Issue 25(2020)
• Publication Date: 2020-06-19
• Subjects: Morpholine -- Borono-Mannich -- Elimination -- Enamine -- Reduction; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2020.131253
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: 2-Hydroxy-3-aryl morpholines are readily prepared from arylboronic acids, aqueous glyoxal, and 1, 2-aminoethanols by a variant of the Petasis borono-Mannich reaction. We now show that the 2-hydroxy-3-aryl morpholines may be deoxygenated to 3-aryl morpholines by treatment with methanesulfonic anhydride and triethylamine to afford intermediate 3, 4-dihydro-2 H -1, 4-oxazines, followed by reaction with a triacetoxyborohydride salt and acetic acid to afford 3-aryl morpholines. This reaction sequence constitutes a three step, "two pot" preparation of 3-aryl morpholines from readily available starting materials (1, 2-aminoethanols, arylboronic acids, and glyoxal) with excellent functional group tolerance and adaptability to scale. Graphical abstract: Image 1 Highlights: 2-Hydroxy-3-arylmorpholines are prepared by Petasis borono-Mannich reaction. 2-Hydroxy-3-arylmorpholines are reduced to 3-arylmorpholines. 2-Hydroxy-3-arylmorpholines are reduced by elimination and reduction. 3, 4-Dihydro-2 H -1, 4-oxazines enamines are intermediates. Elimination is effected by methanesulfonic anhydride and triethylamine.