Terpene Cyclizations inside a Supramolecular Catalyst: Leaving-Group-Controlled Product Selectivity and Mechanistic Studies

The tail-to-head terpene cyclization is arguably one of the most complex reactions found in nature. The hydrogen-bond-based resorcinarene capsule represents the first man-made enzyme-like catalyst that is capable of catalyzing this reaction. Based on noncovalent interactions between the capsule and the substrate, the product selectivity can be tuned by using different leaving groups. A detailed mechanistic investigation was performed to elucidate the reaction mechanism. For the cyclization of geranyl acetate, it was found that the cleavage of the leaving group is the rate-determining step. Furthermore, the studies revealed that trace amounts of acid are required as cocatalyst. A series of control experiments demonstrate that a synergistic interplay between the supramolecular capsule and the acid traces is required for catalytic activity.