ICRED · Iridium Catalyzed Reductive Cyclization Cascades

Iridium Catalyzed Reductive Cyclization Cascades

Amides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of chemical transformations routinely used in organic synthesis. Accordingly, the development of chemoselective carbon-carbon bond forming methodologies arising from the functionalization of the amide functionality should find widespread use across academia and industry. During the course of this project, we have developed a new and technically simple one pot-protocol for synthesising tertiary amine using tertiary amide as starting materials and Grignard reagent as the reactive coupling partner for carbon-carbon bond formation. The project has achieved most of its objectives and milestones for the period, with relatively minor deviations. - New reactivity from amide and lactam feedstock chemicals: Dr Xie has developed new methodologies towards the synthesis of amine derivative through the iridium-catalyzed reductive carbon-carbon bond formation of amide and lactam, managed to apply inter molecular carbon nucleophiles instead of the proposed intra molecular ones. Thus allowed the more general utility of the amide and lactam chemicals. - The development of new complexity generating cascade reactions: Dr Xie carried out the discovery and optimization of a new reductive coupling of amide and Grignard reagent to synthesize tertiary amine derivative and a reductive Ugi-type reactions of tertiary amide by the reductive coupling of amide and isocyanide in the presence of either acid or trimethylsilyl azide. And the later one offered an new access to the synthesis of high value Ugi amino amide and tetrazole compounds. - New enantioselectivity in iridium catalyzed reductive cascades: The researcher has started a program towards the enantioselective synthesis of Ugi-type alpha amino amide, which has come out with some promising results. - New approaches to complex product synthesis: The researcher has successfully applied the new transformations to the synthesis of drugs and bioactive molecules, as well as the derivativation and late stage functionalization of complex bioactive molecules.

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