Palladium-Catalyzed 5-exo-trig Hydroamidation of β,γ-Unsaturated Hydrazones for Synthesis of Dihydropyrazoles

Abstract

Hydroamination reaction is the addition of a N-H unit across the unsaturated C-C bond, which provides a convenient route for the formation of C-N bond. Considerable effort has been directed toward the development of multiple catalytic protocols for the hydroamination reaction in the past decades. Despite appreciable progress in this field, the development of general and practical strategy for the hydroamination of amides remains challenging, because the strong electron-withdrawing substituents (acyl, sulfonyl, or phosphinyl) strongly declined the nucleophilicity of the nitrogen. In this paper, a mild and efficient palladium-catalyzed 5-exo-trig hydroamidation of β,γ-unsaturated hydrazones for the synthesis of dihydropyrazoles has been developed. The reaction employs readily available starting materials, tolerates a wide range of functional groups, and produces a series of valuable dihydropyrazoles in good to high yields (63%～88%) under mild reaction conditions. Furthermore, a gram-scale hydroamidation of 1a afforded the dihydropyrazole 2a in 85% yield. In addition, the deuterium labeling experiment demonstrated that N-H is the hydrogen source in this hydroamidation process.

Palladium-catalyzed intramolecular aza-Wacker-type cyclization of vinyl cyclopropanecarboxamides to access conformationally restricted aza[3.1.0]bicycles

“…Although remarkable process has been made in intramolecular aza-Wacker-type reactions in recent decades, the construction of structurally diverse heterocyclic compounds, including fused and bridged ring compounds, using this strategy remains challenging. 7 To the best of our knowledge, the synthesis of conformationally restricted aza[3.1.0]bicycles from vinyl cyclopropanecarboxamides via intramolecular aza-Wacker oxidation or oxidative amination is not reported in the literature. Herein, we describe our recent efforts toward the Pd-catalyzed ligand-free intramolecular oxidative amidation of vinyl cyclopropanecarboxamides 1 to access conformationally restricted aza[3.1.0]bicycle core 2 via aza-Wacker-type reaction ( Scheme 1e ).…”

Update on the Synthesis of N‐Heterocycles via Cyclization of Hydrazones (2017–2021)

“…[16] However, from 2017 to the present, the use of hydrazone compounds to construct heterocycles has attracted substantial interest from researchers. More than 120 studies [17,18] have been published that should be summarized comprehensively. Studies published before 2017 are mentioned briefly in this review, but the focus of this paper is on the synthesis of nitrogencontaining heterocycles via typical hydrazone methods over the past five years.…”