Late-stage functionalization of biologically compelling natural products, especially challenging C-H bond functionalizations, are currently under investigation. We are interested in enabling selective C-H functionalization in the presence of other reactive functional groups. Current efforts have been focused on employing rhodium(II)-catalyzed C-H carbenoid insertion reactions on alkaloid natural products. Traditionally these have proven to be challenging substrates as the nucleophilic amines present in these compounds can bind to and consequently poison the rhodium(II) catalyst. By identifying suitable reaction conditions we have been able to demonstrate the first examples of rhodium(II)-catalyzed intermolecular C-H insertion into nucleophilic amine-containing molecules. The use of donor-acceptor substituted rhodium carbenoids enables remarkable chemoselectivity: a high tendency towards C-H insertion over aza-ylide formation. A particularly attractive feature of this methodology is that diverse functionalization could potentially be achieved by simply manipulating the reaction conditions. Our insights into the process as well as the  scope and limitations of this exciting development will be discussed.

Late stage C-H functionalization of nitrogen-containing complex natural products via intermolecular rhodium-carbenoid insertion

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.