Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

Abstract

Iodination of carbohydrate-derived 3,6-dihydro-2H-1,2-oxazines of type 3 using iodine and pyridine in DMF furnished 5-iodo-substituted 1,2-oxazine derivatives 4 with high efficacy. The alkenyl iodide moiety of 1,2-oxazine derivatives syn-4 and anti-4 was subsequently exploited for the introduction of new functionalities at the C-5 position by applying palladium-catalyzed carbon–carbon bond-forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano-substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations. This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor.