Multivalent Aminoseptanose Mimetics by Copper‐Catalyzed (3+2) Cycloadditions of Azidomethyl‐Substituted Bicyclic 1,2‐Oxazines

• Published in: European journal of organic chemistry Vol. 27; no. 8
• Main Authors: Bouché, Léa, Zimmer, Reinhold, Reissig, Hans‐Ulrich
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.02.2024; Wiley Subscription Services, Inc
• Subjects: Acetic acid; alkynes; azides; carbohydrate mimetics; Charcoal; Chemistry; Chemistry, Organic; click chemistry; Copper; Hydrogenolysis; Palladium; Physical Sciences; reductions; Room temperature; Science & Technology; Substitutes; Triethylamine; (-)-SUAVEOLINE; reductions; BUILDING-BLOCKS; alkynes; click chemistry; azides; ENANTIOSPECIFIC TOTAL-SYNTHESIS; AJMALINE-RELATED ALKALOIDS; carbohydrate mimetics; ACID PROMOTED REARRANGEMENT; LIGANDS; (-)-RAUMACLINE; AMINO-SUGARS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202301294

Starting from readily available enantiopure azidomethyl‐substituted bicyclic 1,2‐oxazine derivatives and mono‐, di‐ or trialkynes, their copper‐catalyzed (3+2) cycloadditions furnished a series of 1,2,3‐triazolyl‐linked compounds in good yields. These click reactions proceeded smoothly at room temperature when copper iodide as catalyst was used in the presence of triethylamine and tris[(1‐gbenzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]amine as ligand. Generally, the unprotected bicyclic 1,2‐oxazine derivatives seemed to show slightly higher reactivity and provided better yields compared with their silyl‐protected counterparts. Exhaustive hydrogenolysis with cleavage of the 1,2‐oxazine N−O bonds in the presence of palladium on charcoal as promotor is feasible but was found to be capricious. Reasonable results were obtained when acetic acid was employed as cosolvent. By applying these conditions, several of the bicyclic 1,2‐oxazine derivatives were successfully converted into the expected mono‐ or divalent aminooxepine derivatives which can be regarded as aminoseptanose mimetics. Enantiopure azidomethyl‐substituted bicyclic 1,2‐oxazine derivatives and alkynes reacted under copper catalysis to give (multivalent) (3+2) cycloadducts. The reductive removal of the N‐benzyl group and cleavage of the N−O bond furnished aminooxepane derivatives, which can be regarded as septanose mimetics.