A comprehensive study on the synthesis of 5-fluoroalkyl-substituted isoxazoles starting from functionalized halogenoximes is reported. One-pot metal-free [3 + 2] cycloaddition of CF3-substituted alkenes and halogenoximes bearing ester, bromo, chloromethyl, and protected amino groups was developed for the preparation of 5-trifluoromethylisoxazoles. The target 3,5-disubstituted derivatives were obtained in a regioselective manner in good to excellent yield on up to 130 g scale. 5-Fluoromethyl- and 5-difluoromethylisoxazoles were synthesized by late-stage deoxofluorination of the corresponding 5-hydroxymethyl or 5-formyl derivatives, respectively, in turn prepared via metal-free cycloaddition of halogenoximes and propargylic alcohol. An alternative approach based on nucleophilic substitution in 5-bromomethyl derivatives was found to be more convenient for the preparation of 5-fluoromethylisoxazoles. Reaction of isoxazole-5-carbaldehydes with the Ruppert–Prakash reagent was used for the preparation of (β,β,β-trifluoro-α-hydroxyethyl)­isoxazoles. Utility of described approaches was shown by multigram preparation of side-chain functionalized mono-, di-, and trifluoromethylisoxazoles, for example, fluorinated analogues of ABT-418 and ESI-09.

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We investigated the optical properties of heterocyclic azo dyes with different side groups prepared: as powders, in PMMA matrix, and side-chain polymers. We characterized the nonlinear optical effects of these compounds by Z-scan and all-optical poling techniques and supported these experiments with theoretical modeling. It was found that these materials show strong two-photon absorption cross sections exceeding 20 GM, which is 1 order of magnitude stronger than that of similar materials (azobenzene and p-amino­azobenzene). Our study reveals the dominant role of the side-chain system over the guest–host one and stresses the importance of the substituent in the efficiency of the poling process.

A series of NЈ- (3-amino-1H-isoindol-1-ylidene)alkyl (aryl,heteroaryl)carbohydrazides have been synthesized in good yields and their structure and conformational behavior in the solid state and in solution have been studied by X-ray crystallography, NMR spectroscopy, and quantum calculations. (E)/(Z) amide-type isomerism and the dependence of the iso-

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An efficient synthesis (up to a 200 g scale) of 3hydroxypyrrolidin-2-ones bearing alkyl substituents or functional groups at the C-5 position is described. The reaction sequence started from 1,3-dipolar cycloaddition of in situ generated nitrile oxides with (meth-)acrylates into 3-substituted isoxazoline-5carboxylates. The catalytic hydrogenolysis of the isoxazoline N−O bond was optimal upon using H 2 (1 atm) at rt, with the following order of the catalyst activity: Pd−C > Pd(OH) 2 −C > Pt−C. The reactions with Pt−C were more selective for the synthesis of pyrrolidones, while Pd−C provided the fastest conversion rates. The stirring efficiency had a positive impact on conversion rather than elevated temperatures (up to 40 °C) or pressure (up to 50 atm). The diastereoselectivity was governed mainly by steric factors, with a dr of 1:1 to 3:1 (cis-and trans-isomers could be separated). Higher homologues (isoxazolinylacetates and -propanoates) were suitable for the synthesis of 6-or 7-substituted 4-hydroxypiperidones and 5-hydroxyazepanones, respectively. The proposed methods are tolerant to functional groups, including CF 3 (but not CHF 2 or CH 2 Cl), ester, and most N-Boc-protected amines. The utility of hydroxyl groups in lactams was shown by functional group transformations. Hydrogenolysis of C(5)-functionalized isoxazolines, bearing trimethylsilyl, phosphonate, or sulfone groups, was also studied to demonstrate limitations.