Efficient Synthesis of Trifluoromethyl-Substituted 5,6-Dihydro-4H-1,2-oxazines by the Hetero-Diels-Alder Reaction of 1,1,1-Trifluoro-2-nitroso-2-propene and Electron-Rich Olefins

Article abstract of DOI:10.1021/jo00027a058

1,1,1-Trifluoro-2-nitroso-2-propene (1) was generated in situ by treatment of the α-bromo oxime 5 with base.Moderate to excellent yields of the 3-trifluoromethyl-substituted 1,2-oxazines 17-27 were obtained from the reaction of 1 and the silyl enol ethers 6-16, respectively.Other dienophiles, i.e., allyltrimethylsilane, cyclopentadiene, furan, and dihydropyran, upon reaction with 1 provided the cycloadducts 31-34, respectively, in good yield.The results demonstrated that 1 is probably the most reactive heterodiene that has so far been employed in this type of Diels-Alder reaction (i.e., Diels-Alder reaction with inverse electron demand).The mechanism of the reaction and diastereoselectivity of the cycloadditions are discussed.The reaction of 1 with indole and acetyl acetone afforded the oxime 38 and a mixture of the isomers 40-42, respectively.Also, ring opening and other transformations of the trifluoromethyl-substituted 1,2-oxazines were effected.Acid-induced desilylation of the silylated 1,2-oxazines provided oximes like 46 and 48 or 6-hydroxy-1,2-oxazines like 47.Treatment of the 1,2-oxazines with Mo(CO)6 in the presence of trifluoroacetic acid produced 2-trifluoromethyl-substituted pyrroles (e.g., 18 -> 50).The reduction of the 1,2-oxazines afforded either γ-hydroxy oximes (e.g., 19 -> 51) or amino alcohols (e.g., 32 -> 52, 31 -> 55).The reduction of the indole derivative 38 by LiAlH4 provided the trifluoromethyl-substituted tryptamine 56.The results of these explorative studies demonstrated that readily available trifluoromethyl-substituted 1,2-oxazines could be efficiently converted into other compounds that bear a trifluoromethyl group.