Organic Brønsted acid-catalysed enantioselective N-acyliminium cyclisation cascades

Thesis

This thesis concerns the development of the first BINOL phosphoric acid (BPA) catalysed enantioselective N-acyliminium cyclisation reactions and their incorporation into domino sequences that allow for the construction of architecturally complex enantioenriched polycycles in a single step from easily accessible starting materials. More specifically, this thesis deals with the discovery of a BPA-catalysed enantioselective N-acyliminium cyclisation cascade of enol lactones and tryptamines. Its extension to a doubly catalysed process involving gold(I) to cycloisomerise alkynoic acids and a BPA to effect the enantioselective N-acyliminium cyclisation is presented. In addition, the exploitation of this method in highly diastereo- and enantioselective N-acyliminium cyclisations of oxoacids and tryptamines and in a site isolated base-catalysed Michael addition / acid-catalysed N-acyliminium cyclisation cascade is described. A study on the proposed mechanism and model for the origin of enantioselectivity is discussed, based on experimental data and a computational study. As a separate part of our programme, the development of a new class of stronger Brønsted acids, chiral benzenesulphonic acids, is described. The optimisation of the synthetic routes as well as the synthesis of a library of acids is presented and their assessment in precedented reactions is discussed.

Authors: Muratore, M; Michael Muratore

• Publication date: 2010
• DOI: 10.5287/ora-bxvaxr0bd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: cascade; asymmetric; enantioselective; organocatalysis; N-acyliminium; phosphoric; binol; cyclisation; acid; indole; Bronsted
• Subjects: Organic chemistry; Asymmetric catalysis