Catalyst-controlled site-selective dehydrogenation, a stepping stone for C-H oxidations in complex terpenes synthesis.

Abstract

Olefins are a privileged motif present in natural products and pharmaceuticals and serve as reliable entry points for oxygen installation in total synthesis. While dehydrogenation is an efficient strategy to forge olefins in complex organic molecules, limitations of current methods restrict its broader use as a stepping stone toward net site-selective oxidation. Here, we show that catalyst-controlled, site-selective dehydrogenation of multiple β,γ- and γ,δ-C-H bonds, enabled by distinct palladium and copper catalysts, allows oxidation at multiple sites. This approach enables stereo- and/or regioselective oxidation of C-H and C-C double bonds, including oxidation of sterically hindered C-H bonds over more accessible ones in diterpenes. These transformations are not readily achieved using existing chemical or enzymatic methods. The utility of this strategy is demonstrated through the synthesis of ten natural products.