Send to

Choose Destination
Nat Commun. 2015 Jan 12;6:5943. doi: 10.1038/ncomms6943.

Late-stage C-H functionalization of complex alkaloids and drug molecules via intermolecular rhodium-carbenoid insertion.

Author information

Department of Global Discovery Chemistry, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, USA.


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center