Datensatz

Zusammenfassung

The synthesis of new chiral Brønsted acids and their application in the catalytic asymmetric Fischer indolization, a catalytic asymmetric 6π electrocyclization, and the kinetic resolution of homoaldols are presented. In the course of this work, synthetic routes to novel spirocyclic C 2‐symmetric phosphoric acids and disulfonimides were developed. These structures represent new and complementary tools for enantioselective catalysis. In the realization of a catalytic asymmetric Fischer indolization, catalyst poisoning by the basic ammonia by‐product was identified as the major challenge associated with the utilization of only substoichiometric amounts of a chiral Brønsted acid promoter. Different potential solutions to this problem were explored, eventually leading to the first catalytic asymmetric Fischer indolization. This reaction enabled the efficient and highly enantioselective synthesis of 3‐substituted tetrahydrocarbazoles from 4‐substituted cyclohexanone‐derived phenylhydrazones in the presence of a 5 mol% loading of a novel spirocyclic chiral phosphoric acid and an ion exchange resin as ammonia scavenger. Inspired by this project, another class of hydrazones, derived from α,β‐unsaturated ketones, was employed as substrates for the first catalytic asymmetric 6π electrocyclization. The chiral Brønsted acid‐catalyzed cyclization of these substrates – isoelectronic to the 6π electrocyclization of the pentadienyl anion – afforded 2‐pyrazolines in high yields and enantioselectivities. The synthetic utility of the obtained products was exemplified by the development of some highly diastereoselective subsequent transformations. Furthermore, one of the newly developed spirocyclic phosphoric acids was identified as a highly efficient catalyst for the kinetic resolution of γ‐hydroxy acetals via an intramolecular transacetalization reaction. The combination of a kinetic resolution and a parallel kinetic resolution renders this methodology highly efficient for both secondary and tertiary homoaldols. The versatility of this process was amongst others demonstrated in the enantioselective synthesis of a γ‐butyrolactone natural product.