Expanding the chemical space of sp3-enriched 4,5-disubstituted oxazoles via synthesis of novel building blocks

Slobodyanyuk, Evgeniy Y.; Andriienko, Andrii A.; Vashchenko, Bohdan V.; Volochnyuk, Dmitriy M.; Grygorenko, Oleksandr O.

doi:10.1007/s10593-019-02475-9

Cited by 7 publications

(4 citation statements)

References 52 publications

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“…. 22 A 1.5 mL glass vial equipped with a stirrer was charged with 4f (28.6 mg, 0.1 mmol), Cu 2 O (1.4 mg, 0.01 mmol), and ethyl…”

Section: Ethyl (S)-5-(1-((tert-butoxycarbonyl)amino)ethyl)oxazole-4-c...mentioning

confidence: 99%

Copper-Catalyzed [3 + 2] Cycloaddition Reaction of N-Hydroxysuccinimide Ester with Isocyanoacetates for the Synthesis of 4,5-Disubstituted Oxazoles

Wang

Lou

et al. 2023

J. Org. Chem.

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“…. 22 A 1.5 mL glass vial equipped with a stirrer was charged with 4f (28.6 mg, 0.1 mmol), Cu 2 O (1.4 mg, 0.01 mmol), and ethyl…”

Section: Ethyl (S)-5-(1-((tert-butoxycarbonyl)amino)ethyl)oxazole-4-c...mentioning

confidence: 99%

Copper-Catalyzed [3 + 2] Cycloaddition Reaction of N-Hydroxysuccinimide Ester with Isocyanoacetates for the Synthesis of 4,5-Disubstituted Oxazoles

Wang

Lou

et al. 2023

J. Org. Chem.

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“…In line with our continuous efforts to synthesize fluorinated oxazoles, − in this work, we report a comprehensive study on the regioselective synthesis of various 5-(fluoroalkyl)isoxazoles via the [3 + 2] cycloaddition approach involving halogenoximes as the nitrile oxide source, focusing mainly on the preparation of functionalized substrates (e.g., bearing a protected amino group). In addition to that, we have aimed at expanding of chemical space covered by fluorinated isoxazoles with a series of small-molecule building blocks accessible on multigram scale.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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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“…First of all, key intermediates 5 – 7 were prepared in three steps using the procedures reported by us elsewhere . Surprisingly, a dimerization product 8 containing a 10‐membered ring was obtained in 45 % yield (by LC‐MS) instead of the expected 5,6‐dihydro‐4 H ‐pyrrolo[3,4‐ d ]oxazole derivative 9 when 5 reacted with NaH in THF (Table , Entry 1).…”

Section: Resultsmentioning

confidence: 99%

Formation of 10/12/14‐Membered Rings is Favored over 5/6/7‐Membered. An Unexpected Result from Oxazole Chemistry

et al. 2019

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Base‐promoted cyclization of N‐Boc‐ω‐(4‐(chloromethyl)oxazol‐5‐yl)alkylamines led to the corresponding “dimerization” products containing fused 10‐, 12‐, and 14‐membered rings. Experimental data showed that the formation of these ring systems is favored over the corresponding 5‐/6‐/7‐membered ones, which was partially confirmed by DFT calculations; this effect was especially significant in the case of the 5‐/10‐membered pair.

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Expanding the chemical space of sp3-enriched 4,5-disubstituted oxazoles via synthesis of novel building blocks

Cited by 7 publications

References 52 publications

Copper-Catalyzed [3 + 2] Cycloaddition Reaction of N-Hydroxysuccinimide Ester with Isocyanoacetates for the Synthesis of 4,5-Disubstituted Oxazoles

Copper-Catalyzed [3 + 2] Cycloaddition Reaction of N-Hydroxysuccinimide Ester with Isocyanoacetates for the Synthesis of 4,5-Disubstituted Oxazoles

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

Formation of 10/12/14‐Membered Rings is Favored over 5/6/7‐Membered. An Unexpected Result from Oxazole Chemistry

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