Accessing Tricyclic Imines Comprising a 2-Azabicyclo[2.2.2]octane Scaffold by Intramolecular Hetero-Diels–Alder Reaction of 4-Alkenyl-Substituted N-Silyl-1,4-dihydropyridines

Heinrich-Karl A. Rudy; Klaus T. Wanner

doi:10.1055/s-0039-1690619

Synthesis, Inhaltsverzeichnis

Synthesis 2019; 51(22): 4296-4310
DOI: 10.1055/s-0039-1690619

paper

Accessing Tricyclic Imines Comprising a 2-Azabicyclo[2.2.2]octane Scaffold by Intramolecular Hetero-Diels–Alder Reaction of 4-Alkenyl-Substituted N-Silyl-1,4-dihydropyridines

Heinrich-Karl A. Rudy

,

Klaus T. Wanner ∗

Ludwig-Maximilians-Universität München, Department für Pharmazie – Zentrum für Pharmaforschung, Butenandtstr. 5-13, Haus C, 81377 Munich, Germany eMail: klaus.wanner@cup.uni-muenchen.de

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Abstract

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Abstract

Tricyclic imines inheriting a 2-azabicyclo[2.2.2]octane (isoquinuclidine) scaffold were provided with high regioselectivity in moderate to very good yields by a smooth, broadly applicable intramolecular hetero-Diels–Alder reaction of various 4-ω-alkenyl-substituted 1,4-dihydropyridines (DHPs) under trifluoroacetic acid catalysis. The required 4,4-disubstituted 1,4-DHPs were obtained by introduction of ω-alkenyl moieties of varying chain length via diorganomagnesium reagents into the 4-position of diversely 4-substituted pyridines after prior N-activation with triisopropylsilyltriflate.

Key words

intramolecular hetero-Diels–Alder reaction - 2-azabicyclo[2.2.2]octane - polycycles - 1,4-dihydropyridines - diorganomagnesium reagents - heterocycles

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