Synthesis of Novel Tetrahydro-1<i>H</i>-pyrazolo[4,3-<i>c</i>]pyridines <i>via</i> Intramolecular Nitrilimine Cycloaddition

Abstract

The preparation of novel tetrahydro-1H-pyrazolo[4,3-c]pyridines is reported. Pivotal to the synthesis of these compounds was the development of mild reaction conditions to generate a highly functionalized nitrilimine capable of undergoing an intramolecular cycloaddition with a tethered alkyne. The desired cycloadduct was formed as an equal mixture of diastereomers.

Regioselective Synthesis of Mono‐ and Dispiropyrazoline Derivatives via 1,3‐dipolar Cycloaddition with Nitrilimines

“…In the continuation of our work on 1,3‐dipolar cycloaddition reactions , we therefore investigated the possibility to construct this targeted scaffold via 1,3‐dipolar cycloaddition using ( E , E )‐1,3‐bis(arylidene)indan‐2‐ones across diarylnitrilimines. Note that the use of diarylnitrilimines in cycloaddition across alkenes and other dipolarophiles allowing the construction of N ‐heterocyclic systems is well documented in the literature .…”

Nucleophilic Trapping Nitrilimine Generated by Photolysis of Diaryltetrazole in Aqueous Phase

“…Nitrilimines, reactive 1,3-dipoles first reported by Huisgen and co-workers [1], have served as versatile intermediates in the construction of a variety of nitrogen-containing compounds. For example, 1,3-dipolar cycloaddition reactions of nitrilimines with alkenes can produce pyrazoles [2,3], while nucleophilic addition of nitrilimines with amines, thiols or hydroxyls can produce triazenes, thiohydrazones or oxyhydrazones, respectively [4,5,6,7]. These triazene or thiahydrazone skeletons have been successfully applied in the preparation of biologically active, heteroatom-containing compounds including triazoles [8], tetrazines [9], thiadiazines [10] and triazepines [11].…”