Pd(0)-Catalyzed C(sp3)-H Activation for the Synthesis of Natural Products and Cyclopropanes

C-H bonds are ubiquitous in organic substances. That is why, over the past decades, the transition metal-catalyzed intramolecular activation of unactivated C-H bonds has emerged as a powerful tool for synthetic chemists. In particular, selective activation and functionalization of C-H bonds allows a straightforward access to high molecular complexity in an atom- and step-economical fashion and without the need from extensive functionalization of the starting materials.
Our research group being specialized in this particular field, my PhD thesis has been focused on the application of Pd(0)/Pd(II) catalyzed C(sp3)-H activation methods for the total synthesis of complex natural products, along with the development of new methodologies using this approach.
In the first part of this thesis, we report the enantioselective, scalable and divergent total synthesis of two complex dithiodiketodipiperazine natural products (–)-epicoccin G and (–)-rostratin A using a double Pd(0)-catalyzed C(sp3)-H activation strategy.
In the second part of this thesis, we present a new synthetic method to access cyclopropanes using remote functionalization of distal C-H bonds. Overall, taking advantage of the Pd-1,4 shift reactivity, cyclopropanation reaction was performed from intramolecular double C(sp3)-H activation on gem-dialkyl groups, which has been considered for long as an elusive transformation.