Recent Advances in Nitrile Oxide Cycloadditions. Synthesis of Isoxazolines

Abstract

Synthesis of novel heterocyclic compounds continues to be an important and challenging task. Isoxazolines are one such class of heterocyclic molecules of significance, since they are frequently found in many compounds that show significant biological activity. They are also of importance since they can be easily transformed into important functional groups. Nitrile oxide cycloaddition with carbon dipolarophiles represents an easy route to the synthesis of these molecules. Research groups over the past decades have established novel protocols and methods for the synthesis of isoxazolines via dipolar cycloaddition. This review will highlight the success that has been achieved in this field since 2000.

Recent Advances in Intramolecular Nitrile Oxide Cycloadditions in the Synthesis of 2-Isoxazolines

“…(1), such as the hypochlorite or chlorosuccinnimide oxidation and subsequent dehydrohalogenation of oximes I; dehydrosilylation of hydroxamic acid derivatives II by triflic anhydride; or isocyanate-induced dehydration of nitroalkanes III. Additional reagents for the generation of nitrile oxides and their equivalents will appear throughout this review and can be found elsewhere in the literature [5].…”

Synthesis of Oxazoline and Oxazole Derivatives by Hypervalent-Iodine-Mediated Oxidative Cycloaddition Reactions

“…The isoxazoline ring is present in many important heterocycles that are widely used in several areas of chemistry and biomedical sciences. [24][25][26]52 Hypervalent iodine reagents such as (diacetoxyiodo)benzene, [115][116][117][118][119][120][121][122][123][124][125][126][127][128][129] [hydroxy(tosyloxy)iodo]benzene, 130,131 iodosylbenzene, [132][133][134][135] [bis(trifluoroacetoxy)iodo]benzene, 136 (dichloroiodo)benzene, 137 and also in situ generated iodine(III) species, [138][139][140][141] can be used as efficient tools for construction of the isoxazoline ring.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Five-membered heterocycles with nitrogen and oxygen atoms in the ring, such as oxazolines, oxazoles, isoxazolines, and isoxazoles, are particularly important in life-saving drugs, bioactive natural compounds, products of the pharmaceutical industry, synthetic building blocks, and as metal catalyst ligands. [10][11][12]14,16,[24][25][26][27][28][29] Therefore, the reactions forming these heterocyclic rings and those introducing functional groups into these rings represent a hot topic, and numerous important synthetic procedures based on these reactions have been developed. The known procedures often have serious drawbacks, such as harsh reaction conditions, long reaction times, limited substrate scope, or poor yields.…”

“…In particular, numerous synthetic procedures utilizing metal reagents have been developed for efficient and mild syntheses of oxazoline and oxazole derivatives. [10][11][12]14,16,[23][24][25][26][27][28]30 However, some of the metal reagents are expensive, toxic, and rare; therefore, new synthetic methodologies under metal-free and mild conditions have been extensively studied.…”

Oxidative cyclizations of oximes using hypervalent iodine reagents

“…[12][13][14][15][16] Aldoximes and ketoximes are convenient and readily available starting materials for construction of various heterocyclic compounds with nitrogen and oxygen in the ring, which are commonly found in medicinal drugs, bioactive compounds, and natural products. [17][18][19][20][21][22][23][24][25][26] The oxidation of aldoximes 1 using hypervalent iodine(III) reagents 2 produces nitrile oxides 3, which can react in situ with appropriate dipolarophiles such as alkenes 4, alkynes 5, nitriles 6, or aldehydes 7 via the intermolecular 1,3-dipolar cycloaddition to give the corresponding heterocyclic products such as isoxazolines 8, isoxazoles 9, oxadiazoles 10, or dioxazoles 11 (Scheme 1). 13,27 Scheme 1.…”