Solution-Phase Synthesis of a Diverse Library of Benzisoxazoles Utilizing the [3 + 2] Cycloaddition of in Situ-Generated Nitrile Oxides and Arynes

Abstract

A library of benzisoxazoles has been synthesized by the [3 + 2] cycloaddition of nitrile oxides with arynes and further diversified by acylation/sulfonylation and palladium-catalyzed coupling processes. The eight key intermediate benzisoxazoles have been prepared by the reaction of o-(trimethylsilyl)aryl triflates and chlorooximes in the presence of CsF in good to excellent yields under mild reaction conditions. These building blocks have been used as the key components of a diverse set of 3,5,6-trisubstituted benzisoxazoles.

2,2′‐Bis‐substituted Biphenyls by the Addition of Nucleophiles to Benzyne Followed by In Situ Oxidative Homocoupling

“…In the case of 7 or Tf 2 O, only traces of the desired product 3a were formed, as determined by GC-MS. N,NЈ-Diphenyl-p-benzoquinonediimine (8) did not provide a better result (entry 4, Table 1), [22] but with 2,3-dichloropropene (2,3-DCP) as oxidant our desired homocoupling product 3a was isolated in 17 % yield (entry 5, Table 1). [23] However, this reaction was not very clean and several byproducts, which could not be assigned, were observed.…”

“…[4] In addition, they have since been used in polymerization, [5] click chemistry, [6] and various tandem [7] reactions. Moreover, such pericyclic processes have also been applied to the synthesis of pharmacophores [8] and other interesting classes of substances. [9] Along with pericyclic reactions, in situ generated arynes have also been shown to act as efficient acceptors in reactions with various nucleophiles, [10] in "addition/protonation" sequences, [11] and in "addition/trapping" [12] to yield the corresponding mono-or disubstituted benzene derivatives.…”

Synthesis and Properties of Functional Twisted Tolanes

“…N , N ′‐{ethyne‐1,2‐diylbis[(2,1‐phenylene)methylene]}dimethanaminium bis(trifluoroacetate) ( 3 ): A published procedure was used . Trifluoracetic acid (4.5 mL, 58.0 mmol, 30 equiv) was added to a solution of 22 (0.890 g, 1.916 mmol, 1 equiv) in dichloromethane (45 mL) in one portion at rt.…”

The Isoxazole Ring and Its N‐Oxide: A Privileged Core Structure in Neuropsychiatric Therapeutics

“…As such, they have been am ajor research themea sp rimary drug targets for many physiological as well as pathological processes. [88,125] [122][123][124] Some known ROR ligand-acting isoxazoles are shown in Figure 16.…”