Regioselective nucleophilic addition of 3-aryl-5-difluoromethyl-isoxazoles to aldehydes

Synthesis of 5-(Fluoroalkyl)isoxazole Building Blocks by Regioselective Reactions of Functionalized Halogenoximes

“…13 C{ 1 H} NMR (126 MHz, CDCl 3 ): δ 160.0 (q, J = 43.6 Hz), 140.5, 116.9 (q, J = 271 Hz), 108.9 (q, J = 2.2 Hz). 19 C,22.25;H,0.47;N,6.49;Br,Found: C,22.24;H,0.38;N,6.49;Br,36.92.…”

“…7 Hz),131.6,129.7,127.4,127.2,118.3 (q, J = 270 Hz), 105.9 (d, J = 2.4 Hz). 19 3.32;N,5.76. Found: C,54.25;H,2.99;N,5.81.…”

“…13 C{ 1 H} NMR (101 MHz, DMSOd 6 ): δ 159.1 (q, J = 42.7 Hz), 158.3, 117.8 (q, J = 270 Hz), 108.0 (q, J = 2.3 Hz), 62.9, 14.1. 19 3-Phenyl-5-(trifluoromethyl)isoxazole (3b). 71,72 The compound was purified by distillation in vacuo.…”

“…13 C{ 1 H} NMR (101 MHz, DMSOd 6 ): δ 164.2 (d, J = 249 Hz), 162.2, 157.9 (q, J = 41.8 Hz), 129.8 (d, J = 8.9 Hz), 123.7 (d, J = 3.3 Hz), 118.3 (q, J = 270 Hz), 116.7 (d, J = 22.1 Hz), 105.7 (q, J = 2.3 Hz). 19 3-(Thiophen-2-yl)-5-(trifluoromethyl)isoxazole (3e). The compound was purified by column chromatography on silica gel (40 g RediSep column; run length: 74.0 CV; flow rate: 60 mL/min; rack: 16 mm × 150 mm tubes) using hexanes−CHCl 3 (4:1) as eluent.…”

“…It is not surprising therefore that synthesis of fluoroalkyl-substituted isoxazoles have attracted significant interest. A classical approach to the synthesis of these compounds relies on the heterocyclization reaction of fluorinated 1,3-bis-electrophiles and hydroxylamine (Scheme , A). − A similar method involves condensation of enolizable oximes with trifluoroacetates (Scheme , B) . In addition to that, deoxofluorination of the oxygen-containing isoxazoles, for example, alcohols or aldehydes, was described (Scheme , C). , An alternative approach includes [3 + 2] cycloaddition − of fluoroalkyl-substituted alkenes, − alkynes, − or enolizable ketones − and generated in situ nitrile oxides (Scheme , D).…”