Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

Solomin, Vitalii V.; Radchenko, Dmytro S.; Slobodyanyuk, Evgeniy Y.; Geraschenko, Oleksandr V.; Vashchenko, Bohdan V.; Grygorenko, Oleksandr O.

doi:10.1002/ejoc.201900032

Cited by 9 publications

(6 citation statements)

References 108 publications

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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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Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Several protocols for regioselective C−H activation have been developed, [19,20,26,27] but typically were applied to structurally simple oxazoles stabilized by a C2‐(hetero)aryl group. Alternatively, transition metal‐mediated cross‐couplings of 5‐bromooxazoles [27–29] and oxazolyl‐5‐ethers [30] have been realized, but often suffer from limited substrate scope as well as modest stability of the oxazole ring such activated. (Hetero)aryl esters, [31] carbonates, [32] carbamates, [32,33] sulfonates, [34] and sulfamates [32,33,35] have been explored as C−O electrophiles in selected cross‐couplings.…”

Section: Figurementioning

confidence: 99%

Effective C5‐Arylation of Peptide‐Integrated Oxazoles: Almazole D

Oberheide

Arndt

2020

Adv Synth Catal

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An efficient functionalization approach of oxazoles by using Pd‐catalyzed cross‐coupling reactions is reported. Oxazolone formation and subsequent sulfamoylation in situ are facilitated by employing N,N‐diethylsulfamoyl imidazolium triflate. Cross‐couplings provide both oxazole‐arenes and oxazole‐heteroarenes and were compatible with sensitive and epimerization‐prone substrates, as exemplified by the total synthesis of the natural product almazole D.

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“…[19] Driven by important applications of oxazole derivatives, various synthetic methodologies for their synthesis have been developed. The classical approaches to the synthesis of trisubstituted oxazoles include dehydrative cyclization of acyclic precursors described in numerous reviews; [1][2][3] newer methods rely on Ni-catalyzed Suzuki-Miyaura coupling, [21] cross-coupling reactions of 2-, 4-and 5-bromooxazoles, [22] and palladiumcatalyzed CÀ H activation. [23] Notably, direct approaches to highly functionalized oxazoles are rare, thus making a general and efficient procedure to access trisubstituted oxazoles -in particular, those containing both amino and carboxyl groupshighly desirable.…”

Section: Introductionmentioning

confidence: 99%

Functionalized 5‐Amino‐4‐cyanoxazoles, their Hetero‐ and Macrocyclic Derivatives: Preparation and Synthetic Applications

et al. 2021

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An approach to a series of new 5-amino-4-cyanoxazoles is described. Synthesis of the title compounds relied on a twostep sequence including heterocyclization of 2-amido-3,3dichloroacrylonitriles with aliphatic secondary amines (dimethylamine, morpholine), primary aliphatic amines with active functional groups (2-aminoethanol and glycine ethyl ester), and aniline. An efficient and straightforward protocol introduces a carboxylate group at the C-2 position of 5-amino-4-cyanoxazoles, connected to the heterocycle directly or through an aliphatic linker. This carboxylic group is an attractive motif that can be found in a variety of drug-relevant compounds and also used for further modifications. Furthermore, efficient transformations of selected trisubstituted compounds were used to demonstrate their rich synthetic potential -e. g., as precursors to 2-(4-cyano-5-(dimethylamino)oxazol-2-yl)acetamides, oxazole-containing macrocyclic structures, 2-(oxazol-2-yl) acetamides, amino pyrazoles, 3-(4-cyano-5-aminoxazol-2-yl) coumarins, and oxazole amino acids.[a] D.

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Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

Cited by 9 publications

References 108 publications

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

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

Effective C5‐Arylation of Peptide‐Integrated Oxazoles: Almazole D

Functionalized 5‐Amino‐4‐cyanoxazoles, their Hetero‐ and Macrocyclic Derivatives: Preparation and Synthetic Applications

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