DAST Mediated Chemoselective Cyclization

J. Org. Chem. 2019, 84, 4893−4897. DOI:10.1021/acs.joc.8b02179

◆Syntheses of 2-amino-dihydro-1,3-thiazines have been reported via intramolecular cyclization of N-hydroxypropyl thioureas.

◆Unfortunately, these protocols failed for the cyclization of 6, probably due to the bulky and high electron-withdrawing nature of the CF3 group

◆To selectively obtain 1,3-thiazine 7 over 1,3-oxazine 8, we hypothesized that use of oxophilic electrophiles, which can react with the hydroxyl group and then serve as an efficient leaving group, could be suitable fo ractivation of the hydroxyl group.

◆The lack of reactivity of the hydroxyl in 6 with MsCl and Tf2O, due to the electronwithdrawing nature of the CF3 group, would limit the formation of the leaving groups, thereby resulting in poor yields.

◆DAST-mediatedcyclization enabled access to 1,3-thiazine 7 on a gram scale.