Mechanistically guided survey of enantioselective palladium-catalyzed alkene functionalization

The mechanistic rationalization for the evolution of Pd-catalyzed alkene functionalization processes is discussed. Specifically, this review focuses on the use of different ligand types and counterion effects that enabled the progression from the early methodologies, restricted to cyclic olefins, to the current strategies, which tolerate the use of unbiased acyclic olefins. Pd(0) complexes can promote enantioselective coupling of alkenes with aryl and alkenyl halides and pseudohalides. Organometallic reagents and, in rare examples, non-functionalized molecules can also be used as coupling partners in Pd(II) catalyzed processes. Enantioselective coupling of heteroatoms to alkenes can also be facilitated by Pd(II) complexes. The first examples of intermolecular Wacker and aza-Wacker reactions are discussed. Palladium-catalyzed alkene functionalization was discovered more than 60 years ago and is now a commonly used strategy for the synthesis of pharmaceuticals and materials. The development of asymmetric variants of this reaction is described in this short review. The review is organized around the mechanistic challenges that have hampered the development of these transformations for various substrate classes, as well as the strategies, ligand classes, and additives that have been introduced to overcome them. New methodologies for Heck, oxidative Heck, dehydrogenative Heck, and Wacker-type reactions are highlighted, with a special focus on the progression from cyclic to acyclic to electronically unbiased olefin substrates. Palladium-catalyzed alkene functionalization was discovered more than 60 years ago and is now a commonly used strategy for the synthesis of pharmaceuticals and materials. The development of asymmetric variants of this reaction is described in this short review. The review is organized around the mechanistic challenges that have hampered the development of these transformations for various substrate classes, as well as the strategies, ligand classes, and additives that have been introduced to overcome them. New methodologies for Heck, oxidative Heck, dehydrogenative Heck, and Wacker-type reactions are highlighted, with a special focus on the progression from cyclic to acyclic to electronically unbiased olefin substrates. Pd(II)-catalyzed process that adds a nitrogen nucleophile to an unsaturated system forming a new N–C bond and preserving the degree of unsaturation of the substrate. These processes require the presence of an oxidant to regenerate the Pd(II) catalyst. sequence of β-hydrogen eliminations and migratory insertions that isomerizes an unsaturation through an aliphatic system. palladium-catalyzed arylation or alkenylation of alkenols to yield remotely functionalized aldehydes or ketones. The process is initiated by a migratory insertion into the alkene moiety and a series of β-hydrogen eliminations and migratory insertions to transfer the unsaturation to the alcohol moiety. The final oxidation of the alcohol into a carbonyl group serves as a ‘thermodynamic sink’ for terminating the chain-walking process. a process that facilitates the reaction of one enantiomer of the starting material over the other enantiomer. As a result, the remaining starting material increases its optical purity. addition across a π-bond of a Pd(II) complex and a heteroatom, the latter of which may or may not be coordinated to the palladium. a reaction that cleaves an A–B bond forming two new covalent bonds between a metal center (M) and the A and B residues (A–M–B). During this process, the metal is formally oxidized by two electrons and the coordination number of the metal center increases. This is often the first step of organometallic catalytic cycles. opposite reaction of oxidative addition where two metal–ligand bonds are cleaved and a new bond between those ligands is formed. During this process, the metal is formally reduced by two electrons and the coordination number of the metal center decreases. This is typically the last step of organometallic catalytic cycles. species that formally donate one electron and accept one electron to form a non-dative covalent bond when binding to a metal. Hydrides, alkyl groups, and halogens are examples of these types of ligands.