Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

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Introduction of Fluorine and Fluorine-Containing Functional Groups

Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates

Iron Catalysis in Organic Synthesis

Isatins As Privileged Molecules in Design and Synthesis of Spiro-Fused Cyclic Frameworks

The 3,3′-disubstituted oxindole structural motif is a prominent feature in many alkaloid natural products, which include all kinds of tetrasubstituted carbon stereocenters, spirocyclic or not, all-carbon or heteroatom-containing. The catalytic asymmetric synthesis of the tetrasubstituted carbon stereocenter at the C-3 position of the oxindole framework integrates new synthetic methods and chiral catalysts, reflects the latest achievements in asymmetric catalysis, and facilitates the synthesis of sufficient quantities of related compounds as potential medicinal agents and biological probes. This review summarizes the recent progress in this area, and applications in the total synthesis of related bioactive compounds.

Catalytic Asymmetric Synthesis of Oxindoles Bearing a Tetrasubstituted Stereocenter at the C‐3 Position

Homochiral catalysts that can effect asymmetric transformations are invaluable in the production of optically active molecules. Researchers are actively pursuing the design of new ligands and organocatalysts by exploiting concepts derived from the application of bifunctional and C2-symmetric catalysts. Many homochiral catalysts containing amines, ethers, alcohols, and phosphines as electron-pair donors have been successfully developed.Amine N-oxides are highly polar substances. Despite their pronounced capacity as electron-pair donors, N-oxides have been underutilized in asymmetric reactions; they have only made a visible impact on the field in the preceding decade. Systematic studies have instead largely focused on pyridine- or quinoline-based scaffolds in organosilicon and coordination chemistry. The application of chiral tertiary amine N-oxides has not been widely pursued because of the difficulty of controlling the chirality at the tetrahedral nitrogen of the N-oxide moiety. In this Account, we outlin...

Chiral N,N′-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

The enantioselective synthesis of 3-functionalized oxindole derivatives has experienced an explosive development. This minireview introduces the recent application of rare earth (RE) metal complex catalysts in the synthesis of targeted frameworks. The direct addition reactions of 3-substituted oxindoles or isatins are described, together with a discussion of the catalytic mechanism and related transformations to pharmaceuticals.

Recent progress in enantioselective synthesis of C3-functionalized oxindoles: rare earth metals take action

A class of conformationally flexible ligands composed of a tertiary amino oxide–amide backbone and a straight-chain alkyl spacer was developed. These C2-symmetric chiral N,N′-dioxide ligands could be straightforwardly synthesized from readily available amino acids and amines. They act as neutral tetradentate ligands to bind a wide variety of metal ions. Non-planar cis-α M(N,N′-dioxide) complexes enable an intriguing and easily fine-tuned chiral platform for a number of asymmetric reactions. Privileged N,N′-dioxide ligands frequently show wide substrate generality and exceptional levels of stereocontrol for a specific catalytic reaction. We describe approaches to the ligand design and synthesis, structure and bonding in coordination complexes, and the recent developments in asymmetric catalysis.

Chiral N,N′-dioxide ligands: synthesis, coordination chemistry and asymmetric catalysis

ConspectusCatalytic asymmetric cycloadditions and cascade cyclizations are a major focus for the enantioselective construction of chiral carbo- and heterocycles. A number of chiral Lewis acids and organocatalysts have been designed for such reactions. The development of broadly applicable catalysts bearing novel chiral backbones to meet the demands of various applications is an ongoing challenge. Approximately 10 years ago, we introduced a group of conformationally flexible C2-symmetric N,N′-dioxide amide compounds, which represent a new class of privileged ligands. The coordination of the four oxygens of a chiral N,N′-dioxide around a central metal generates an octahedral tricyclometalated Lewis acid catalyst that can carry out various enantioselective reactions. In this Account, we summarize our recent studies on asymmetric cycloadditions between various dienophiles and dienes, dipoles and dipolarophiles, and cascade cyclizations catalyzed by chiral N,N′-dioxide–metal complexes. In principle, these uniq...

Lili Lin

Papers

Chiral N,N′-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions

Recent progress in enantioselective synthesis of C3-functionalized oxindoles: rare earth metals take action

Chiral N,N′-dioxide ligands: synthesis, coordination chemistry and asymmetric catalysis

Asymmetric Cycloaddition and Cyclization Reactions Catalyzed by Chiral N,N′-Dioxide–Metal Complexes

Amide-based bifunctional organocatalysts in asymmetric reactions