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DYKAT and Desymmetrization Strategies for the Synthesis of Axially Chiral Heterobiaryls

Dr. D. José María Lassaletta Simon, Dra. D.ª Rosario Fernández Fernández y Dr. D. Abel Ros Laó

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Resumen

The main objective of this PhD thesis is the development of methodologies for the synthesis of axially chiral heterobiaryls through asymmetric functionalization of readily available precursors. Specifically, the approaches to achieve this goal are based on DYKAT (Dynamic Kinetic Asymmetric Transformation) and desymmetrization processes. Additionally, the synthesized products present a great potential in catalytic applications.

In chapter 1, which serves as an introduction, different strategies for the synthesis of axially chiral heterobiaryls are depicted, focusing on those based on Asymmetric Catalysis as the key tool for the introduction of the desired functional groups.

Chapter 2 describes the development of a DYKAT process combined with a Buchwald-Hartwig reaction using racemic and configurationally stable heterobiaryl electrophiles. This protocol has been successfully applied to the synthesis of Isoquinoline-Amino Naphthalene (IAN) and related derivatives in high yields and excellent enantioselectivities. In addition, some of these IAN-type amines were transformed into the corresponding N-oxides, and these derivatives proved to be catalytically active for the asymmetric allylation and crotylation of aromatic aldehydes.

In chapter 3, configurationally labile substrates were desymmetrized through an Ir(I)-catalyzed C–H hydroarylation. Thus, this strategy enables the synthesis of heterobiaryls with both axial and central chirality with highly regio-, diastereo- and enantioselectivities.

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