ABSTRACT
Palladium-catalyzed cascade cyclizations (PCCs) are powerful synthetic tools that enable rapid assembly of polycyclic scaffolds. Palladium complexes can promote a variety of carbon-carbon and carbon-heteroatom bond-forming reactions with high chemo-, enantio-, and diastereoselectivity. The combination of multiple ring-forming elementary steps into a single cascade sequence can allow complex structures to be accessed with high step economy. This strategy has been employed to access natural products in several distinct classes, including the mitomycins, dragmacidins, isoryanodane diterpenes, and ergot alkaloids. In this tutorial review, we demonstrate how PCCs have expedited natural product synthesis by enabling the formation of both C-C and C-X (X = O, N) bonds in a single synthetic operation.
ABSTRACT
[figure: see text] A tandem anionic 5-exo-dig cyclization/Claisen rearrangement sequence was used to effect a facile, "one-pot" conversion of an appropriately substituted 4-alkyn-1-ol to the tetracyclic carbon core structure of phorbol. The synthesis was conducted using readily available nonracemic starting materials to provide the target structure as a single enantiomer in high chemical yield.
