This Review summarizes the development of catalytic asymmetric dearomatization (CADA) reactions. The CADA reactions discussed herein include oxidative dearomatization reactions, dearomatization by Diels-Alder and related reactions, the alkylative dearomatization of electron-rich arenes, transition-metal-catalyzed dearomatization reactions, cascade sequences involving asymmetric dearomatization as the key step, and nucleophilic dearomatization reactions of pyridinium derivatives. Asymmetric dearomatization reactions with chiral auxiliaries and catalytic asymmetric reactions of dearomatized substrates are also briefly introduced. This Review intends to provide a concept for catalytic asymmetric dearomatization.

In recent years, Hantzsch esters and their related organic hydride donors have been widely utilized in biomimetic approaches of asymmetric transfer hydrogenation (ATH) reactions. Various compounds containing C=C, C=N and C=O unsaturated functionalities could be reduced in the presence of organocatalysts or transition metal complexes, affording versatile chiral building blocks in high yields and excellent enantioselectivities under mild conditions. In this critical review, recent advances in this area are summarized and classified according to unsaturated functional groups being reduced and catalytic systems employed (91 references).

In this review, we summarize the origin and advancements of iridiumcatalyzed asymmetric allylic substitution reactions during the past two decades. Since the first report in 1997, Ir-catalyzed asymmetric allylic substitution reactions have attracted intense attention due to their exceptionally high regio-and enantioselectivities. Ircatalyzed asymmetric allylic substitution reactions have been significantly developed in recent years in many respects, including ligand development, mechanistic understanding, substrate scope, and application in the synthesis of complex functional molecules. In this review, an explicit outline of ligands, mechanism, scope of nucleophiles, and applications is presented.

Phenols are widely used as starting materials in both industrial and academic society. Dearomatization reactions of phenols provide an efficient way to construct highly functionalized cyclohexadienones. The main challenge to make them asymmetric by catalytic methods is to control the selectivity while overcoming the loss of aromaticity. In this tutorial review, an up to date summary of recent progress in CADA reactions of phenol and aniline derivatives is presented.

No abstract

Chiral ferrocene ligands have been widely used in asymmetric catalysis. The advantages of using ferrocene as a scaffold for chiral ligands are described, particularly those regarding planar chirality, rigid bulkiness, and ease of derivatization. The role of planar chirality in 1,2- and 1,1'-disubstituted ferrocene systems is discussed. By using a bulky ferrocene fragment, novel ferrocene ligands were designed, and high enantioselectivity and regioselectivity were achieved in the allylic substitution reaction of monosubstituted allyl substrates. Using the tunable electronic properties of a diphosphine-oxazoline ferrocenyl ligand, the regioselectivity of the intermolecular asymmetric Heck reaction was also examined.

The asymmetric Friedel-Crafts reaction is one of the most powerful methods to synthesize optically active aromatic compounds. Particularly, the Friedel-Crafts alkylation of arenes with unsaturated compounds activated by chiral Brønsted acids provides direct access to enantiopure aromatic derivatives with perfect atom economy. In this tutorial review, recent progress in the development of chiral Brønsted acid-catalyzed asymmetric Friedel-Crafts reactions is presented.

Dearomatization reactions serve as powerful methods for the synthesis of highly functionalized, three-dimensional structures starting with simple planar aromatic compounds. Among processes of this type, catalytic asymmetric dearomatization (CADA) reactions are attractive owing to the large number of aromatic compounds that are readily available and the fact that they enable direct access to enantiopure polycycles and spirocycles, which frequently are key structural motifs in biologically active natural products and pharmaceuticals. However, as a consequence of their high stabilities, arenes only difficultly participate in dearomatization reactions that take place with high levels of enantioselectivity. Transition-metal-catalyzed asymmetric allylic substitution reactions have been demonstrated to be powerful methods for enantioselective formation of C-C and C-X (X = O, N, S, etc.) bonds. However, the scope of these processes has been explored mainly using soft carbon nucleophiles, some hard carbon nucleophiles such as enolates and preformed organometallic reagents, and heteroatom nucleophiles. Readily accessible aromatic compounds have been only rarely used directly as nucleophiles in these reactions. In this Account, we present the results of studies we have conducted aimed at the development of transition-metal-catalyzed asymmetric allylic dearomatization reactions. By utilizing this general process, we have devised methods for direct dearomatization of indoles, pyrroles, phenols, naphthols, pyridines, and pyrazines, which produce various highly functionalized structural motifs bearing all-carbon quaternary stereogenic centers in a straightforward manner. In mechanistic investigations of the dearomatization process, we found that the five-membered spiroindolenines serve as intermediates, which readily undergo stereospecific allylic migration to form corresponding tetrahydro-1H-carbazoles upon treatment with a catalytic amount of TsOH. It is worth noting that no notable loss of the enantiomeric excess of the spiroindolenine derivatives takes place during the rearrangement process as a consequence of the intervention of a "three-center-two-electron"-type transition state, a proposal that has gained support from the results of DFT calculations. Equally intriguing, upon tuning of the electronic nature of the tethers, pyrroles or indoles undergo unprecedented Ir or Ru catalyzed intramolecular allylic alkylation promoted dearomatization/migration reactions. The operation of this novel reaction pathway provides additional information leading to a greater mechanistic understanding of the transition-metal-catalyzed enantioselective intramolecular functionalizations of pyrroles and indoles. The combined results of this effort provide not only methods for the efficient synthesis of highly enantioenriched fused and spiro polycycles but also novel strategies in the field of asymmetric catalysis.