Interceptive [4 + 1] Annulation of in Situ Generated 1,2-Diaza-1,3-dienes with Diazo Esters: Direct Access to Substituted Mono-, Bi-, and Tricyclic 4,5-Dihydropyrazoles

Abstract

In situ derived acyclic and cyclic 1,2-diaza-1,3-dienes (DDs) were engaged in interceptive [4 + 1] annulation strategy with diazo esters (DEs). The catalytic activity of inexpensive copper(II) chloride allows the direct synthesis of mono-, bi-, and tricyclic 4,5-dihydropyrazole-5-carboxylic acid derivatives in a process that circumvents the use of an anhydrous and inert atmosphere.

Sequential MCR via Staudinger/Aza-Wittig versus Cycloaddition Reaction to Access Diversely Functionalized 1-Amino-1H-Imidazole-2(3H)-Thiones

“…To validate our hypothesis we began to explore the process step by step. Thus, α-chlorohydrazone derivative 1a [26,27,28,29,30] (2.0 mmol) dissolved in THF (9.0 mL) subjected to α-azidation using an ice-cooled aqueous solution of NaN 3 [31] (2.0 mmol/1.0 mL) under magnetic stirring at room temperature. After the evaporation of the solvent and an appropriate extraction, the α-azidohydrazone derivative 2a was obtained in 70% yield.…”

“…All the commercially available reagents and solvents were used without further purification. α-Halohydrazones 1a – k were synthesized by known procedures [26,27,28,29,30]. Chromatographic purification of compounds was carried out on silica gel (60–200 μm).…”

Organocatalyzed Asymmetric Reaction Using α-Isothiocyanato Compounds

“…Despite rapid progress in organocatalytic asymmetric cascade reactions with α-isothiocyanato compounds as reagents has been made, the types of chemical reaction in this area are still limited in number. Accordingly, it might be one promising and exciting research field to develop novel asymmetric cascade reactions between the α-isothiocyanato compounds and other accepters, such as nitrosoarenes [46], N-sulfinylanilines [47], oxaziridines [48], nitrones [49], azomethine imines [50], α-halo N-acyl hydrazones [51], epoxidation [52], et al Moreover, making further insight into the reaction mechanism concerning α-isothiocyanato reagents will facilitate the rapid development of the new methodology in this realm. In summary, the research by employing α-isothiocyanato compounds for the construction of complex heterocyclic compounds via organocatalytic asymmetric cascade process has broad development space.…”

Synthesis of 4,5-Dihydropyrazoles via Palladium-Catalyzed Cyclization Reactions of β,γ-Unsaturated Hydrazones with Aryl Iodides

“…Xiao’s group explored a new strategy to synthesize 4,5-dihydropyrazoles through halocyclization with β,γ-unsaturated hydrazones and N -bromosuccinimide (Scheme , eq 2) . Afterward, Nicolini’s group reported a copper-catalyzed interceptive [4 + 1] annulation of 1,2-diaza-1,3-dienes with diazo esters, leading to substituted 4,5-dihydropyrazoles (Scheme , eq 3) …”

“…4 Afterward, Nicolini's group reported a copper-catalyzed interceptive [4 + 1] annulation of 1,2-diaza-1,3-dienes with diazo esters, leading to substituted 4,5-dihydropyrazoles (Scheme 1, eq 3). 5 In recent years, metal-catalyzed functional grouping of allenes to synthesize various heterocyclic compounds has become a research hotspot. 6−10 In particular, the study of pyrazoline compounds remains a challenge for researchers.…”