DYKAT and desymmetrization strategies for the synthesis of axially chiral heterobiaryls

Abstract

The main objective of this PhD thesis is the development of new methodologies for the synthesis of axially chiral heterobiaryls through asymmetric functionalization of this type of systems. In this regard, the approaches to achieve this goal will be based on a DYKAT (Dynamic Kinetic Asymmetric Transformation) and a desymmetrization process. Additionally, the synthesised products present a great potential in catalytic applications. In Chapter 1, which severs as an introduction, different strategies for the synthesis of axially chiral heterobiaryls are depicted, focusing on the strategies based on the catalytic asymmetric functionalization of heterobiaryls. On the other hand, in chapter 2, the first of the two developed methodologies during this PhD thesis is described. Thus, this methodology relies on a DYKAT process combined with a Buchwald-Hartwig reaction using racemic and configurationally stable heterobiaryl electrophiles. Then, this protocol has been successfully applied to the synthesis of IAN-type amines in high yields and good to excellent enantioselectivities. In chapter 3, another approach is employed for the synthesis of chiral heterobiaryls. In this case, configurationally labile substrates were desymetrized 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.