Stereoselective Directed Cationic Cascades Enabled by Molecular Anchoring in Terpene Cyclases

Cascade reactions appeared as a cutting‐edge strategy to streamline the assembly of complex structural scaffolds from naturally available precursors in an atom‐, as well as time, labor‐ and cost‐efficient way. We herein report a strategy to control cationic cyclization cascades by exploiting the ability of anchoring dynamic substrates in the active site of terpene cyclases via designed hydrogen bonding. Thereby, it is possible to induce “directed” cyclizations in contrast to established “non‐stop” cyclizations (99:1) and predestinate cascade termination at otherwise catalytically barely accessible intermediates. As a result, we are able to provide efficient access to naturally widely occurring apocarotenoids, value‐added flavors and fragrances in gram‐scale by replacing multi‐stage synthetic routes to a single step with unprecedented selectivity (>99.5 % ee) and high yields (up to 89 %).