Recent Advances in Transition-Metal-Catalyzed Asymmetric Functionalization of Enamides

Abstract

Enamides, as prefunctionalized electron-rich heteroatom-substituted alkenes represent a powerful platform to synthesize useful nitrogen-containing natural products and bioactive molecules. This review discloses recent progress in the transition-metal-catalyzed enantioselective functionalization of enamides, including the Heck reaction, hydrofunctionalization, and difunctionalization, with a focus on the general scope, current limitations, stereochemical reaction control, and mechanistic aspects.1 Introduction2 Asymmetric Heck Reaction of Enamides3 Asymmetric Hydrofunctionalization of Enamides3.1 Nickel Catalysis3.2 Copper Catalysis3.3 Rhodium Catalysis3.4 Iridium Catalysis4 Asymmetric Difunctionalization of Enamides4.1 Palladium Catalysis4.2 Nickel Catalysis4.3 Copper Catalysis5 Summary and Outlook

Fluorocyclisation of Oximes to Isoxazolines Through I(I)/I(III) Catalysis

“…Given this tendency, the gauche conformational preferences of X−C α −C β −X motifs (synclinal exo / endo, Figure 1, top), and the importance of fluorine in drug discovery, [15–23] fluorinated isoxazolines are attractive bioisosteres of the parent scaffolds ( Figure 1, right). In contrast to trifluoromethyl‐containing analogues, such as 4 , [1,2,24–32] routes to monofluoromethylated derivatives are comparatively under‐represented ( vide infra ) [33,34] . Therefore, motivated by the potential of fluorinated isoxazolines, [21] it was envisaged that a direct fluorocyclisation route to isoxazolines from β,γ‐unsaturated oximes by I(I)/I(III) catalysis would be enabling.…”

Asymmetric Organocatalyzed Cyclization Cascade Reactions of 3,3-Difluoro-2-aryl-3H-indoles and Enamides

“…Furthermore, chemists have shown growing interest in the direct functionalization of β-C­(sp 2 )-H bonds in enamides. Despite significant progress, the main strategies employed for the functionalization of β-C­(sp 2 )-H bonds in enamides usually rely on transition-metal-catalyzed activation of C–H bonds and oxidative coupling via radicals . (Scheme a).…”

Lewis Acid-Mediated Electrophilic Thiolative Difunctionalization of Enimides: Rapid Access to β-Amino Sulfides

“…Direct functionalization of enamides and their analogues is a popular approach for the construction of nitrogen-containing molecules. , Due to the highly polarized carbon–carbon double bond, they generally possess high reactivities to give the desired products with good regio- and diastereoselectivities. Importantly, the formed products are a class of amine derivatives in no need of the introduction of external nitrogen sources .…”