ChemInform Abstract: Synthesis of Isoxazoles by Hypervalent Iodine‐Induced Cycloaddition of Nitrile Oxides to Alkynes.

Abstract

Synthesis of Isoxazoles by Hypervalent Iodine-Induced Cycloaddition of NitrileOxides to Alkynes. -Cycloaddition of nitrile oxides, generated in situ from corresponding aldoximes (I) with a range of substituted alkynes (II) affords regioselectively 3,5-disubstituted isoxazoles (III). The reaction proceeds exceedingly fast with strained cyclic alkynes, e.g. (IV). The mild reaction conditions together with the good tolerance toward various functional groups, furthermore allow the preparation of peptide and nucleoside conjugates, e.g. (VII). -(JAWALEKAR, A. M.; REUBSAET, E.; RUTJES, F. P. J. T.; VAN DELFT*, F. L.; Chem. Commun. (Cambridge) 47 (2011) 11, 3198-3200, http://dx.doi.org/10.1039/c0cc04646a ; Inst. Mol. Mater., Radboud Univ. Nijmegen, NL-6525 ED Nijmegen, Neth.; Eng.) -K. Wilckens 25-124

Diastereoselective Synthesis of 1,3-Diyne-Tethered Trifluoromethylcyclopropanes through a Sulfur Ylide Mediated Cyclopropanation/DBU-Mediated Epimerization Sequence

“…In another example, reaction of compound 4 with nitrile oxide, generated in situ from benzaldehyde oxime, afforded isoxazole 9 in 78% yield. 17 The relative configuration of compound 9 was determined to be trans by a single-crystal X-ray diffraction method.…”

“…5, 135.0, 129.8, 129.3, 123.6 (q, J = 273.8 Hz), 82. 9, 70.2, 68.2, 66.2, 65.4, 30.8, 28.8, 26.1 (q, J = 37.5 Hz), 17 (2-(5-Hydroxy-5-methylhexa-1,3-diyn-1-yl)-2-(trifluoromethyl)cyclopropyl)(4-nitrophenyl)methanone (3d). According to the typical procedure, 1d (45 mg, 0.2 mmol) was transformed using 2a (61 mg, 0.3 mmol), MeCN (2 mL), and DBU (15 mg, 0.1 mmol).…”

“…1H), 1.57 (dd, J = 8.5, 5.3 Hz, 1H), 1.51 (s, 6H), 0.98 (dd, J = 6.6, 3.6 Hz, 6H); 13 C{ 1 H}NMR (125 MHz, CDCl 3 ) δ 201.8, 123.5 (q, J = 273.8 Hz), 82. 7,70.7,68.2,66.4,65.5,53.3,31.2,30.9,25.7 (q,J = 37.5 Hz),24.6,22.7,22.5,17. Ethyl 2-(5-Hydroxy-5-methylhexa-1,3-diyn-1-yl)-2-(trifluoromethyl)cyclopropane-1-carboxylate (3q). According to the typical procedure, 1q (30 mg, 0.2 mmol) was transformed using 2a (61 mg, 0.3 mmol), MeCN (2 mL), and DBU (15 mg, 0.1 mmol).…”

“…After purification over silica gel (petroleum ether/ethyl acetate 9:1− 5:1), the desired cyclopropane 3w was obtained (58 mg, 75%) as a colorless oil: 1 H NMR (500 MHz, CDCl 3 ) δ 7.88 −7.84 (m, 2H), 7.69−7.65 (m, 2H), 3.70 (t, J = 5.9 Hz, 2H), 3.19 (dd, J = 8.5, 7.2 Hz, 1H), 2.48 (t, J = 6.2 Hz, 2H), 2.14−2.12 (m, 1H), 1.87 (s, 1H), 1.74 (dd, J = 8.5, 5.5 Hz, 1H); 13 C{ 1 H}NMR (125 MHz, CDCl 3 ) δ 190. 9,135.4,132.3,129.9,129.2,123.6 (q,J = 273.8 Hz),77.5,68.9,66.8,66.0,60.5,28.7,26.1 (q,J = 37.5 Hz),23.6,17. General Procedure for Preparing Compound 4 and 5. Grainy NaOH (27 mg, 0.66 mmol, 2.2 equiv) was added under a nitrogen atmosphere to a solution of 3a or 3g (0.30 mmol, 1.0 equiv) in toluene (5 mL).…”

Oxidation-Induced “One-Pot” Click Chemistry

“…41 Analogously, the presence of a terminal alkyne in combination with phenyliodine bis- (trifluoroacetate) (PIFA) provided isoxazole 20. 42 The PIDAinduced oxidation activation was also compatible with click chemistry of DIBO-functionalized molecules. 40 Even the oxidative cycloaddition of oximes to maleimides in the presence of a catalytic amount of iodonium species has been described.…”