An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

Abstract

Summary2-Aroylmethylidene-1,2,3,4-tetrahydroquinolines with the appropriate substituents can be suitable precursors for the synthesis of alkaloids from Galipea officinalis (cuspareine, galipeine, galipinine, angustureine). However, only two, rather low-yielding procedures for their synthesis are described in the literature. We have developed a simple and efficient protocol for an intramolecular, palladium or copper-catalysed amination of both chloro- and bromo-substituted 3-amino-1,5-diphenylpent-2-en-1-ones leading to the above-mentioned tetrahydroquinoline moiety. The methodology is superior to the methods published to date.

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

“…The condensation of 79 with Meldrum’s acid afforded the coumarin 81 in good yield (74%). Compound 81 was reduced and converted to propanoic acid derivative 82 via internal decarboxylation mediated by formic acid [ 53 ]. The subsequent S N Ar between 82 and 3,5-difluorobenzonitrile ( 83 ) in dimethyl sulfoxide (DMSO) formed the diaryl ether intermediate 84 , which was, in turn, activated to acyl chloride ( 85 ) by the addition of oxalyl chloride to yield the bicyclic system 86 via an internal Friedel-Crafts intramolecular reaction.…”

Synthesis of N‐Substituted Condensed Tetrahydropyridine‐Based Enaminones via Palladium‐Catalyzed Intramolecular C–N Cross‐coupling

“…Nuclear Overhauser effect spectroscopy reveals E configuration on their exocyclic double bond, which was confirmed also in the solid state by X-ray (Supporting Information). It is an opposite to their NH analogs, where Z configuration with N-H···O═C hydrogen bond was found [22].…”

“…Within them, the C–N cross‐coupling variant (Buchwald–Hartwig reaction) is probably the most widespread carbon‐heteroatom bond‐forming reaction, and protocols allowing successful N ‐arylations of practically all imaginable substrates can be found in the literature . Compared with other substrates, enaminones and related compounds are still rather neglected substrates from this point of view . Owing to the lowered nucleophilicity of their nitrogen atom, enaminones can be challenging substrates for this kind of transformation.…”

“…Owing to the lowered nucleophilicity of their nitrogen atom, enaminones can be challenging substrates for this kind of transformation. Recently, we have worked out a fundamentally novel approach to exocyclic tetrahydroquinolines via an intramolecular C–N cross‐coupling of the appropriate enaminones (Scheme ). However, the methodology has been surveyed only for limited number of substrates, and only primary enaminones were used.…”