Zinkvermittelte Hydrohydrazinierung von terminalen Alkinen – eine effiziente Dominosynthese von Indolen

Abstract

Indol‐Klickchemie: Indole sind wichtige Bausteine in Naturstoffen und Medikamenten. Die Suche nach besseren Katalysatoren für eine intermolekulare Hydrohydrazinierung zur Synthese von Indolen führte nun zu Zinksalzen; diese ermöglichen eine einfache Eintopfsynthese vielfältig substituierter Indole aus Arylhydrazinen und terminalen Alkinen. So wurden pharmakologisch interessante Indolbausteine selektiv in Gegenwart von Zn(OTf)2 oder ZnCl2 erhalten (siehe Schema).

Zirconium‐Catalyzed Multistep Reaction of Hydrazines with Alkynes: A Non‐Fischer‐Type Pathway to Indoles

“…[1,2] For these transformations there are relatively few examples of early-transition-metal catalysts, in particular from Group 4. Examples include the titaniumcatalyzed syntheses of N-heterocycles reported by Odom, Beller, and others, [3][4][5][6] involving a catalytic hydrohydrazination of an alkyne and subsequent transformations of the resulting hydrazones, which may either occur by direct coupling with other unsaturated organic substrates [3] or a Fischer-type conversion to indoles. [5] Little is known about the reaction mechanisms of these transformations although the stoichiometric reactivity of titanium hydrazides is the subject of growing interest.…”

Zinc-Catalyzed Synthesis of Pyrazolines and Pyrazoles via Hydrohydrazination

“…Over the past years, we investigated catalytic reactions of arylhydrazines with alkynes in more detail . Most recently, we succeeded in an intermolecular zinc-mediated and -catalyzed hydrohydrazination reaction of alkynes, which allows a general synthesis of substituted indoles . Following these investigations, we discovered that the reaction of phenylhydrazine 1a with 3-butynol 2 in the presence of a stochiometric amount of zinc chloride did not result in the expected indole motif.…”

“…Apparently, in the first step the hydrohydrazination of 3-butynol gave the corresponding arylhydrazone. In general, the arylhydrazone undergoes Fischer indole cyclization in the presence of a stochiometric amount of Lewis acid, such as ZnCl 2 . However, in the case of 3-butynol, the pyrazoline was formed by an unusual nucleophilic substitution of the hydroxy group.…”

Palladium‐Catalyzed Amination and Sulfonylation of 5‐Bromo‐3‐[2‐(diethylamino)ethoxy]indoles to Potential 5‐HT6 Receptor Ligands

“…[6] For some time we have been interested in the improvement and exploration of methodologies for the synthesis and functionalization of indoles. [7,8] For example, we developed a one-pot synthesis of tryptamines and trypto-pholes via titanium-catalyzed hydrohydrazination of chloro-and silyloxo-substituted alkynes.…”