Stereoconvergent synthesis of N-Boc-(2R, 3S)-3-hydroxy-2-phenylpiperidine. Issue 12 (21st March 2019)

• Record Type: Journal Article
• Authors: Velasco, Manuel; Hernández, Ulises; Terán, Joel L.; Gnecco, Dino; Orea, María L.; Aparicio, David M.; Gómez-Calvario, Víctor; Bernès, Sylvain; Juárez, Jorge R.
• Is Part Of: Tetrahedron letters. Volume 60:Issue 12(2019)
• Page Start: 820
• Page End: 824
• Publication Date: 2019-03-21
• Subjects: 3-Hydroxypiperidine -- Chiral lactam -- α-Hydroxylation -- Stereoconvergent reduction; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2019.02.005
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Cis- and trans -2-substituted-3-hydroxypiperidines are medicinally important. Green α-hydroxylation and stereoconvergent reduction were crucial in this methodology. Molecular oxygen as a green and sustainable oxidant was employed in this synthesis. Abstract: The stereoconvergent synthesis of N -Boc-(2 R, 3 S )-3-hydroxy-2-phenylpiperidine from ( R )-1-(2-(( tert -butyldimethylsilyl)oxy)-1-phenylethyl)piperidin-2-one is described. The key steps involved are α-hydroxylation of quiral lactam with O2, stereoconvergent reduction of ( R )- or ( S )-3-(benzyloxy)-piperidin-2-one with Red-Al® which afforded in both cases the trans -bicyclic oxazolidine in high stereoselectivity after chromatographic purification and a stereospecific Grignard addition to chiral bicyclic oxazolidine.