Site-Selective Functionalization of Linear Diterpenoids through U-Shaped Folding in a Confined Artificial Cavity

Even flexible linear substrates are conformationally fixed within the hydrophobic confined cavities of enzymes. This enables preorganization of the substrates and their positioning in close proximity to the active center to facilitate stereo- and site-selective reactions. Here, we demonstrate the site-selective electrophilic addition of linear diterpenoids within a self-assembled coordination cage. The reactions proceed through folding of the linear substrates into a U-shaped conformation, which results in noncovalent protection of internal C═C bonds to enhance the site selectivity.