A facile stereoselective synthesis of 2-perfluoroalkyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles

Synthesis of Organofluoro Compounds Using Methyl Perfluoroalk-2-ynoates as Building Blocks

“…The 1,3-dipolar cycloadditions of cyclic nitrones 18 with methyl perfluoroalk-2-ynoates 1 proceeded smoothly in dichloromethane (DCM) at room temperature, affording the 2-perfluoroalkyl-3a,4,5,6-tetrahydroimidazo[1,5-b]isoxazoles 19 as the sole product with 76-98% yields (Scheme 6). [16] The fact that only one diastereoisomer was obtained demonstrates that the reaction was a concerted process guided by the Woodward-Hoffmann rules. [17] When the linear molecule of perfluoroalkylated butynoate approaches planar dipole N-oxide 18 with the perfluoroalkyl group being oriented towards the oxygen atom of the N-oxide function, there are four different routes via 20, 21, 22, or 23.…”

“…Since 1,3‐dipolar cycloadditions of nitrones with dipolarophiles provide a variety of isoxazole derivatives,15 and considering that electron‐deficient alkynes such as methyl perfluoroalk‐2‐ynoates 1 are also good dipolarophiles, our group reported an efficient and convenient process for the synthesis of the regiospecific 2‐perfluoroalkyl‐substituted isoxazoles with high diastereoselectivity. The 1,3‐dipolar cycloadditions of cyclic nitrones 18 with methyl perfluoroalk‐2‐ynoates 1 proceeded smoothly in dichloromethane (DCM) at room temperature, affording the 2‐perfluoroalkyl‐3 a ,4,5,6‐tetrahydroimidazo[1,5‐ b ]isoxazoles 19 as the sole product with 76–98% yields (Scheme ) 16…”

4‐Isoxazolines: Scaffolds for Organic Synthesis

“…[21] The 2-perfluoroalkyl-tetrahydroimidazo [1,5-b]isoxazoles 34 can be obtained from the cyclic nitrones and methyl 2-perfluoroalkynoates in a highly diasteroselective and regioselective fashion. [22] The isoxazolino [4,5-c]quinoline ring system has been prepared by sequential double annulation starting from the acyclic β-(2-aminophenyl)-α,β-ynones 35 (Scheme 9) and the N-methylnitrones 36. [23] The initial regioselective 1,3-dipolar cycloaddition reactions lead to the 4-isoxazolines 37, which undergo condensation to give the quinoline nucleus.…”

Facile synthesis of (polyfluoro)alkanesulfinyl 4-isoxazolines: a stepwise solvent- and catalyst-free approach or a one-pot process in water

“…3 The incorporation of these groups benefits the transformation not only by inducing regioselectivity but also by introducing extra handles for product derivation and decreasing activation energy. Several catalyst-free 1,3-dipolar cycloadditions [28][29][30][31][32][33][34][35][36] for the synthesis of 4-isoxazolines have been reported, and most of them required elevated reaction temperatures in organic solvents, cyclic nitrones or alkynes activated by two electron-withdrawing groups. Sulfoxides play a pivotal role in chemistry and biology.…”

“…1). For instance, Cao and co-workers reported (formal) 1,3-dipolar cycloadditions between perfluoroalk-2-ynoates and cyclic nitrones 32 or N -hydroxyphthalimide 52 at room temperature without catalysts, delivering the corresponding bicyclic 4-isoxazolines in good yields (Fig. 1a and b).…”