Use of Iodoacetylene as a Dipolarphile in the Synthesis of 5-Iodoisoxazole Derivatives

Abstract

Iodoacetylene 1 was prepared in situ from the reactions of ethynylmagnesium bromide or tributyl(ethynyl)tin with iodine. It was used as a dipolarphile in the [2 + 3] cyclization reaction with 1,3-dipolar nitrile oxide derivatives to produce 2-(5-iodoisoxazol-3-yl)pyridine 2 and 3-(4-fluorophenyl)-5-iodoisoxazole 8 in good yield (70-90%). Subsequently, several 5-substituted isoxazole derivatives 3 were obtained by Pd-catalyzed reactions. [reaction: see text]

Expeditious Lead Optimization of Isoxazole-Containing Influenza A Virus M2-S31N Inhibitors Using the Suzuki–Miyaura Cross-Coupling Reaction

“…31, 32 To this end, we chose N-[(5-bromo-1,2-oxazol-3-yl)methyl]adamantan-1-amine 17a and phenylboronic acid as a model reaction for reaction condition optimization (Table 1). Using microwave irradiation, a series of Suzuki coupling conditions with variations in catalyst, solvent, base, and reaction time were explored (Table 1).…”

Configurational assignment of carbon, silicon and germanium containing propynal oximes by means of 13C1H, 13C13C and 15N1H spin–spin coupling constants

“…Oximes and their derivatives are widely used in the synthesis of the nitrogen containing heterocyclic compounds, especially pyrroles with the alkyl, cycloalkyl, aryl and hetaryl substituents, as well as pyrroles condensed with the aliphatic macrocycles, terpenic and steroid structures, as reviewed recently by Schmidt and Mikhaleva. 1 Oximes have been used as building blocks in the synthesis of the biologically active nitriles, 2 amides (Beckmann rearrangement), 3 nitrones, 4 nitriloxides, 5 isoxazoles 6 and other compounds recognized as potential drugs in medicine.…”

Ruthenium‐Catalyzed Cycloadditions of 1‐Haloalkynes with Nitrile Oxides and Organic Azides: Synthesis of 4‐Haloisoxazoles and 5‐Halotriazoles

“…Similarly, bromoisoxazole 21 was converted to the butyl acrylate 55 and allyl 56 derivatives, albeit in modest yield, by using slightly modified published protocols 27a. 29b, c, 39…”

“…[28] However, examples of high yielding reactions involving 1-haloalkynes and nitrile oxides remain remarkably scarce. [29] For example, thermal cycloadditions of nitrile oxides and 1-haloalkynes often either require alkynes substituted with highly activated hypervalent iodine species [30] or a large excess of one of the reactants [29c] and/or controlled addition of the nitrile oxide component. [29b] Despite these precautions, these reactions still often result in mixtures of regioisomers with low to moderate yields.…”