Details

Autor(en) / Beteiligte

• He, Jing
• Hamann, Lawrence G.
• Davies, Huw M. L.
• Beckwith, Rohan E. J.

Titel

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

Ist Teil von

• Nature communications, 2015-01, Vol.6 (1), p.5943-5943, Article 5943

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.