Mini-Review: Organic Catalysts in the 1,3-Dipolar Cycloaddition Reactions of Nitrile Oxides

Abstract

In 1961, Huisgen categorized the nitrile oxides (NOs) as a member of a broader class of 1,3-dipoles that were capable of undergoing 1,3-dipolar cycloaddition (DC) reactions. Nevertheless, the cycloaddition (CA) reactions of NOs to alkenes and alkynes are in many cases hampered by the tendency to the dimerization of the NO to the related furoxan (1,2,5-oxadiazole-2-oxide). In addition, although monosubstituted alkenes and alkynes show high regioselectivity in their cycloadditions with NOs, 1,2-disubstituted derivatives often give mixtures of regioisomers. Catalyzed NOs cycloadditions constitute in many cases an appropriate response to these problems and, in particular, the metal catalyzed cycloaddition reactions have been extensively used. However, the cost, toxicity and removal of trace amounts of the metal residues from desired products is quite costly and challenging, while crucial, especially in the pharmaceutical industry. Obviously, alternative pathways under metal-free conditions to fulfill the metal-catalyzed reactions are highly appealing. The present review is devoted to the consideration of the use of organic molecules as catalysts for 1,3-dipolar cycloaddition reactions of nitrile oxides. CONTENTS

[3 + 2] Cycloaddition of nitrile oxides to dichloropropenes and 1,3‐dichlorobut‐2‐ene: A regioselectivity issue

“…Cycloaddition of nitrile oxides (NOs) to alkenes [1] and alkynes [2,3] is a convenient way to obtain isoxazolines and isoxazoles in one preparative step. These compounds are well-known to possess wide-range biological activity, which applied in medicinal chemistry [4][5][6][7]. In recent years, the method has been intensively developed; organocatalytic approaches [7], non-standard conditions and media [8], and mechanochemical activation [9] have become widespread.…”

“…These compounds are well-known to possess wide-range biological activity, which applied in medicinal chemistry [4][5][6][7]. In recent years, the method has been intensively developed; organocatalytic approaches [7], non-standard conditions and media [8], and mechanochemical activation [9] have become widespread.…”

The Interplay between Kinetics and Thermodynamics in Furan Diels–Alder Chemistry for Sustainable Chemicals Production

“…What distinguishes the furan-diene DA reactions from other [4+ +2] cycloadditions is the reactionsr eversibility at near ambient temperatures.I ndeed, the position of the DA equilibrium can generally be shifted in ac ontrolled, predictable,a nd tunable manner,a tt emperatures ideally suited for e.g.,m aterial science applications.F or this reason, the furan DA coupling has been extensively exploited in various macromolecular applications built around reversibility,s uch as responsive materials [4][5][6][7] and drug delivery systems. [8,9] In contrast, other important areas of application require stability rather than reversibility,a sg enerally seen for instance in bioconjugation, [10] natural product synthesis, [11][12][13][14][15] drug dis-covery [16] and the synthesis of renewables-based chemical commodities (Figure 1). [17][18][19][20][21] In such cases,f urther synthetic elaboration of the relatively labile DA adduct is in competition with the kinetically accessible cycloreversion pathway, posing amajor challenge (Figure 2A).…”

Efficient Catalytic Synthesis of Condensed Isoxazole Derivatives via Intramolecular Oxidative Cycloaddition of Aldoximes

“…The 1,3-dipole cycloaddition reaction is one of the most powerful methods to construct five-membered heterocycles [16][17][18][19][20][21][22][23][24][25][26]. The cycloaddition of nitrile oxides with alkenes and acetylenes is often used in the synthesis of isoxazoles and isoxazolines [27][28][29][30][31][32][33][34][35][36][37]. However, nitrile oxides are unstable species usually generated in situ from aldoximes under appropriate conditions [38][39][40].…”