N-tosyl-1,2,3-triazoles as scaffolds for morpholines: the total synthesis of (–)-chelonin A

Substituted morpholine derivatives appear frequently in biologically active compounds and thus novel routes towards such structures are of great synthetic interest. Herein, we report the total syntheses of chelonin A, a morpholine-derived marine natural product with reported antibacterial and anti-inflammatory activity. The key step in this process was a rhodium carbenoid 1,3-insertion into a bromohydrin O–H bond, followed by annulation, leading to a 2,6-disubstituted-3,4-dihydro-2H-1,4-oxazine core. This work was then extended to deliver the first asymmetric total synthesis of (–)-chelonin A using an enantioenriched bromohydrin, prepared in turn via asymmetric transfer hydrogenation of an α-bromoketone.