Late-stage C–H functionalization of complex alkaloids and drug molecules via intermolecular rhodium-carbenoid insertion
Alkaloids constitute a large family of natural products possessing diverse biological properties. Their unique and complex structures have inspired numerous innovations in synthetic chemistry. In the realm of late-stage C–H functionalization, alkaloids remain a significant challenge due to the prese...
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Published in | Nature communications Vol. 6; no. 1; p. 5943 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
12.01.2015
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Alkaloids constitute a large family of natural products possessing diverse biological properties. Their unique and complex structures have inspired numerous innovations in synthetic chemistry. In the realm of late-stage C–H functionalization, alkaloids remain a significant challenge due to the presence of the basic amine and a variety of other functional groups. Herein we report the first examples of dirhodium(II)-catalysed intermolecular C–H insertion into complex natural products containing nucleophilic tertiary amines to generate a C–C bond. The application to a diverse range of alkaloids and drug molecules demonstrates remarkable chemoselectivity and predictable regioselectivity. The capacity for late-stage diversification is highlighted in the catalyst-controlled selective functionalizations of the alkaloid brucine. The remarkable selectivity observed, particularly for site-specific C–H insertion at
N
-methyl functionalities, offers utility in a range of applications where efficient installation of synthetic handles on complex alkaloids is desired.
The ability to functionalize a C–H bond is useful in complex organic syntheses, but the scope of this approach is sometimes limited by its sensitivity to basic amines. Here, the authors achieve functionalization of amine-containing natural products by site-selective rhodium-carbene-mediated C–H insertion. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms6943 |