Part I: Palladium-catalyzed alkylation of alkenes using epoxides. Part II: Palladium-catalyzed asymmetric wacker-type anti-attack of alkenes

Abstract

This dissertation describes two types of palladium-catalyzed cross-coupling reactions that achieve alkene functionalization. The first type focuses on epoxides as the alkylating reagent in the Heck-type radical process, which will be discussed in the first chapter. The second type highlights the Wacker-type addition of cycloalkenes in the novel enantioselective three-component couplings. This will be presented in the last two chapters. In chapter one, we reported palladium-catalyzed alkylation of alkenes using epoxides. The reaction of epoxides and alkenes provides a highly atom economical access to valuable homoallylic alcohols. In previous reports, successful examples were limited to cobalt catalysis in harsh conditions. Hence, we reported the additive Et3NHI as the halide ion source to facilitate the ring opening of an epoxide, which tolerated sensitive functional groups in the tandem Heck-type alkylation. In reactions of unsymmetrical epoxides, a new C−C bond is predominantly formed at the less-hindered position, and the stereocenters of the epoxides are fully retained. In chapter two, we described an asymmetric alkoxyallenylation and azaallenylation of cycloalkenes using propargylic acetates and heteroatom nucleophiles. It is a novel methodology to achieve a three-component Wacker-type addition of mono-olefins via anti-attack in an enantioselective fashion. The choice of an electron-deficient furyl-MeOBIPHEP ligand is crucial to the reactivity, diastereocontrol and enantiocontrol of this transformation. Besides alcohols, other nucleophiles such as carboxylic acids, phenols, water and electron-deficient aryl amines are also good coupling partners in this catalytic system. Furthermore, this reaction can also be applied to the concise synthesis of chiral 3-benzylpyrrolidines. In the last chapter, we developed a palladium-catalyzed asymmetric allenyl (hetero)arylation of cyclic alkenes through a stereospecific Wacker-type anti-attack. In this method, asymmetric alkylation of heteroarenes through anti-nucleopalladation can be accompanied by the introduction of an allenyl group onto the alkene, thus allowing a maximal increase in molecular complexity. The reaction proceeds smoothly with some electron-rich arenes like tertiary anilines and a broad range of heteroarenes including N-H indoles, N-protected indoles, pyrroles, furans and thiophenes.