"Striving for the ultimate process chemistry synthesis" and “Catalytic asymmetric dearomatisation (CADA)reactions”

Dr. Debra Wallace

“Striving for the ultimate process chemistry synthesis – the importance of mechanistic understanding for reaction optimisation”

This seminar will discuss the development of two recent Merck compounds, Relebactam, a β-lactamase inhibitor being developed for treatment of serious antibiotic resistant bacterial infections and Suvorexant a dual Orexin antagonist recently approved in the US and Japan for treatment of sleep disorder. The talk will discuss synthetic development of the compounds, from the Medicinal Chemistry route, followed by an initial scale-up route suitable for generating kilogram quantities of material. The requirements for an ideal manufacturing route, including cost, robustness, minimal environmental impact and quality of product will be outlined and these principles applied to show how a final approach, considered appropriate for manufacturing implementation was discovered for both target molecules. In each case a detailed mechanistic study of a key reaction will be presented to show how these studies guided final optimisation.

Prof. Shu-Li You

“Catalytic asymmetric dearomatisation (CADA) reactions”

Asymmetric dearomatisation reactions are particularly attractive methods in organic synthesis given the facts that the starting materials arenes are highly abundant and readily available, and the dearomatisation reaction would provide direct access to compounds bearing quaternary carbon centre, polycycles and spirocycles. However, due to the extra stability of “aromaticity” of the arenes, their dearomatisation reaction with good enantioselective control has been rarely studied. In this talk, the progress from the You laboratory on the development of catalytic asymmetric dearomatisation processes will be introduced. Direct asymmetric dearomatisation reactions of various aromatic compounds were realised with a proper choice of catalysts.

1. Zhuo, C.-X.; Zheng, C.; You, S.-L. Transition-metal-catalyzed Asymmetric Allylic Dearomatization Reactions Acc. Chem. Res. 2014, 47, 2558-2573.

2. Zhuo, C.-X.; Zhang, W.; You, S.-L. Catalytic Asymmetric Dearomatization Reactions. Angew. Chem. Int. Ed. 2012, 51, 12662-12686.