Rapid Construction of a Benzo-Fused Indoxamycin Core Enabled by Site-Selective C-H Functionalizations

T Aaron Bedell; Graham A B Hone; Damien Valette; Jin-Quan Yu; Huw M L Davies; Erik J Sorensen

doi:10.1002/anie.201602024

Rapid Construction of a Benzo-Fused Indoxamycin Core Enabled by Site-Selective C-H Functionalizations

Angew Chem Int Ed Engl. 2016 Jul 11;55(29):8270-4. doi: 10.1002/anie.201602024. Epub 2016 May 20.

Authors

T Aaron Bedell¹, Graham A B Hone¹, Damien Valette², Jin-Quan Yu³, Huw M L Davies², Erik J Sorensen⁴

Affiliations

¹ Frick Chemistry Laboratory, Department of Chemistry, Princeton University, Washington Road, Princeton, NJ, 08544, USA.
² Department of Chemistry, Emory University, USA.
³ Department of Chemistry, The Scripps Research Institute, USA.
⁴ Frick Chemistry Laboratory, Department of Chemistry, Princeton University, Washington Road, Princeton, NJ, 08544, USA. ejs@princeton.edu.

PMID: 27206223
DOI: 10.1002/anie.201602024

Abstract

Methods for functionalizing carbon-hydrogen bonds are featured in a new synthesis of the tricyclic core architecture that characterizes the indoxamycin family of secondary metabolites. A unique collaboration between three laboratories has engendered a design for synthesis featuring two sequential C-H functionalization reactions, namely a diastereoselective dirhodium carbene insertion followed by an ester-directed oxidative Heck cyclization, to rapidly assemble the congested tricyclic core of the indoxamycins. This project exemplifies how multi-laboratory collaborations can foster conceptually novel approaches to challenging problems in chemical synthesis.

Keywords: C−H bond activation; natural products; palladation; rhodium carbenes; synthetic methods.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.