Formal [3 + 3] Cycloaddition Reactions between Electron-Deficient Cyclopropenes and Hydrazones: A Route to Alkyl 1,4,5,6-Tetrahydropyridazine-3-carboxylates

Abstract

A formal [3 + 3] cycloaddition reaction between alkyl 2-aroyl-1-chlorocyclopropanecarboxylates 1 and common hydrazones 2 was developed. This process readily proceeded in diastereo-and regioselective fashion and gave alkyl 1,4,5,6tetrahydropyridazine-3-carboxylates in high yields under mild basic conditions. Treatment of the annulation products with DDQ leads to the formation of functionalized pyridazine-3-carboxylates, analogues of nicotinic acid ester.

Visible Light Mediated Photocatalytic N-Radical Cascade Reactivity of γ,δ-Unsaturated N-Arylsulfonylhydrazones: A General Approach to Structurally Diverse Tetrahydropyridazines

“…As a consequence, many efforts have been dedicated to new strategies for the construction of these nitrogen heterocycles: among those are [4 + 2] cycloaddition of azoalkenes, − 1,2-diaza-1,3-dienes, , or diazenes, and [3 + 3] formal cycloadditions exploiting cyclopropyl derivatives and hydrazones. , Nevertheless, the need for available starting materials and a good compatibility of reaction conditions with several functional groups has been the driving force for the use of other cyclization strategies. In this context, hydrazones represent an appealing alternative, − being easy to prepare and displaying a very peculiar reactivity. − Many synthetic approaches exploiting them have been reported, like palladium , and copper mediated cyclizations, , but especially visible light-mediated processes.…”

Construction of heterocyclic rings from cyclopropenes

“…In the presence of Cs 2 CO 3 , a variety of alkyl 2-aroyl-1-chlorocyclopropanecarboxylates and commonly available hydrazones readily underwent formal [3 + 3] cycloaddition reactions in regio- and diastereoselective fashion, giving alkyl 1,4,5,6-tetrahydropyridazine-3-carboxylates 139 in high yields (Scheme 24). 39 This reaction has the merits such as wide substrate scope, simple work-up and mild conditions. Moreover, the annulation product 139 can be smoothly oxidized with DDQ into substituted alkyl pyridazine-3-carboxylate, a nicotinate analogue.…”

Synthesis of Pyridazine Derivatives via Aza-Diels–Alder Reactions of 1,2,3-Triazine Derivatives and 1-Propynylamines

“…A wide array of interesting applications has facilitated the development of synthetic methods for pyridazines with different substituents . Therefore, extensive efforts have been directed toward developing new strategies for the construction of these nitrogen heterocycles including [4 + 2] annulation of alkoxyallenes with 1,2-diaza-1,3-dienes, [4 + 2] annulation of hydrazines with 1,4-bifunctional compounds, [4 + 2] annulation of ketene N , S -acetals and N -tosylhydrazones, formal [3 + 3] cycloaddition of cyclopropene derivatives and hydrazones, [3 + 3] annulation of aldehyde hydrazones and α,β-unsaturated nitrile, catalytic three-component annulations in one-step procedures, and multistep synthesis involving a diaza-Wittig reaction . Despite these achievements, a more efficient metal-free synthesis of pyridazines under neutral conditions is highly desirable to expand the library of substituted pyridazines.…”