Unprecedented Direct Asymmetric Total Syntheses of 5,8’‐Naphthylisoquinoline Alkaloids from their Fully Substituted Precursors Employing a Novel Nickel/N,N‐ligand‐Catalyzed Atroposelective Cross‐Coupling Reaction

A general and concise synthetic pathway for the preparation of four different 5,8’‐coupled naphthylisoquinoline alkaloids, employing a specially developed nickel/N,N‐ligand‐catalyzed atroposelective Negishi coupling is reported. In the first reported direct atroposelective coupling of the fully subs...

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Bibliographic Details
Published in:Chemistry : a European journal 2023-11, Vol.29 (61), p.e202302070-e202302070
Main Authors: Berthold, Dino, van Otterlo, Willem A. L.
Format: Article
Language:English
Subjects:
Alkaloids
Chemical reactions
Chemistry
Cross coupling
Ligands
Methylation
Naphthalene
Nickel
Precursors
Protecting groups
Substitutes
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Summary:A general and concise synthetic pathway for the preparation of four different 5,8’‐coupled naphthylisoquinoline alkaloids, employing a specially developed nickel/N,N‐ligand‐catalyzed atroposelective Negishi coupling is reported. In the first reported direct atroposelective coupling of the fully substituted precursors, the naturally occurring cross‐coupled products were generally obtained directly in reasonable yields and high enantiomeric purities. For the synthesis of the cross‐coupling precursors, we employed a modification of Bringmann's known approach to the dihydroisoquinoline compounds and a newly developed route for the naphthalene building blocks. For the latter 1,8‐dioxynaphthalene precursors, our strategy utilized Hartwig's borylation/methylation approach and included the efficient installation of orthogonal protecting groups.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202302070