Hydrazones as Substrates in the Synthesis of Isoxazolidines via a KOH-Promoted One-Pot Three-Component Cycloaddition with Nitroso Compounds and Olefins

Abstract

Hydrazones have been employed as the starting materials in a KOH-mediated one-pot three-component cycloaddition with readily accessible nitroso compounds and olefins to construct various isoxazolidines. Compared with diazo compounds as starting materials, this methodology could afford a wider range of products in good to excellent yields and diastereoselectivities for most substrates, and hydrazones are cheaper, more accessible, and safer substrates. The experimental study shows that the choice of suitable hydrazones is crucial.

Cu(OAc)2-catalyzed three-component cycloaddition of malonates, nitrosoarenes and alkenes: access to isoxazolidines

“…On the basis of the above-mentioned results and relevant literature, 5–12,13 a plausible reaction mechanism is proposed, as shown in Scheme 6. First, the complexation of Cu(OAc) 2 with intermediate 2a′ tautomerized from diethyl malonate 2a forms intermediate I , which then undergoes a nitroso-ene reaction with nitrosobenzene 1a to generate the hydroxylamine intermediate II .…”

“…6 More recently, our group reported three independent transition-metal-free methods for the construction of isoxazolidines by employing α-carbonyl sulfoxonium ylides, N -alkyl nitrones and hydrazones as the key starting materials through three-component reactions with nitrosoarenes and olefins. 7 Notably, metal-catalyzed multi-component cycloadditions are among the most efficient strategies and alternative methods for accessing these structural motifs. For instance, Cu-catalyzed three-component processes involving functionalized olefins, arylenes, and nitrosoarenes have been well documented to construct these scaffolds by Huang, Liu and their co-workers, respectively (Scheme 1A).…”

Synthesis of 3,4,5-Trisubstituted 1,2,4-Triazoles via I2-Catalyzed Cycloaddition of Amidines with Hydrazones

“…Substrates such as hydrazones 1 and amidines 2 were separately synthesized according to the corresponding literature procedures. They are all known compounds.…”

Catalyst- and additive-free three-component construction of isoxazolidinyl nucleosides and azoles via 1,3-dipolar cycloaddition

“…In addition, although catalyst-mediated generation of nitrones from diazocarbonyl compounds and nitrosoarenes has been well demonstrated, 9 a catalyst-free strategy for the synthesis of isoxazolidine compounds via three-component reactions of diazocarbonyl compounds, nitrosoarenes and alkenes has never been observed. In continuation of our interest in the multicomponent synthesis of isoxazolidinyl rings, 10 herein, we will report a novel catalyst- and additive-free construction of isoxazolidinyl nucleoside analogues via one-pot three-component cycloaddition of readily available diazo compounds, nitrosoarenes and vinyl nucleosides. Additionally, this method is also suitable for the preparation of isoxazolidinyl azoles and isoxazolidinyl indole by using vinyl azoles and vinyl indole as starting materials.…”