An iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of naphthol derivatives is described. Challenges confronted in this reaction include chemoselectivity between carbon and oxygen atoms as nucleophilic centers, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all-carbon quaternary stereocenter. In the presence of an iridium catalyst generated from [{Ir(dbcot)Cl}₂] (dbcot=dibenzocyclooctatetraene) and a new THQphos (tetrahydroquinolinedinaphthophosphoramidite) ligand, various spironaphthalenones were obtained with up to greater than 95:5 C/O selectivity, greater than 95:5 d.r., and 99 % ee, thus providing a general method for the dearomatization of naphthols.

An iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of naphthol derivatives is described. Challenges confronted in this reaction include chemoselectivity between carbon and oxygen atoms as nucleophilic centers, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all-carbon quaternary stereocenter. In the presence of an iridium catalyst generated from [{Ir(dbcot)Cl}₂] (dbcot=dibenzocyclooctatetraene) and a new THQphos (tetrahydroquinolinedinaphthophosphoramidite) ligand, various spironaphthalenones were obtained with up to greater than 95:5 C/O selectivity, greater than 95:5 d.r., and 99 % ee, thus providing a general method for the dearomatization of naphthols.

Recent advances in dearomatization through halofunctionalization reactions are summarized in this Minireview. Two general categories of strategies are currently employed in this field. On one hand, the reaction can be initiated with electrophilic halogenation at an alkyne or alkene moiety. The resulting halonium ion intermediate is then captured by a pendant aromatic ring at the ipso position, affording the dearomatization product. On the other hand, electrophilic halogenation can directly take place at a substituted arene, and the final dearomatization product is furnished by deprotonation or intramolecular nucleophilic trap. Highly enantioselective variants have been realized in the latter case by organocatalysis or transition metal catalysis. By applying these methods, various valuable halogenated polycyclic molecular architectures have been obtained from readily available starting materials.

The highly efficient synthesis of the enantioenriched spiroindolines by iridium-catalyzed asymmetric allylic dearomatization and reduction is presented. Spiroindolines containing three contiguous stereogenic centers were obtained with excellent diastereo- and enantioselectivity. In addition, a chiral tryptamine derivative could be easily accessed in good yield with excellent ee value through an unprecedented dearomatization/retro-Mannich/hydrolysis cascade reaction of an indole derivative.

An intermolecular asymmetric dearomatization reaction of β-naphthols with nitroethylene through a chiral-thiourea-catalyzed Michael reaction is described. Enantioenriched functionalized β-naphthalenones with an all-carbon quaternary stereogenic center could thus be easily constructed from simple naphthol derivatives in good yields and excellent enantioselectivity (up to 79 % yield, 98 % ee).

A highly efficient catalytic asymmetric dearomatization of naphthols by means of an electrophilic amination reaction catalyzed by chiral phosphoric acid is presented. This protocol provides a facile access to functionalized β-naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity (up to 99 % yield, up to 96 % ee).

The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98 % yield and 99 % ee.

The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]₂ (cod=1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

The highly efficient synthesis of the enantioenriched spiroindolines by iridium-catalyzed asymmetric allylic dearomatization and reduction is presented. Spiroindolines containing three contiguous stereogenic centers were obtained with excellent diastereo- and enantioselectivity. In addition, a chiral tryptamine derivative could be easily accessed in good yield with excellent ee value through an unprecedented dearomatization/retro-Mannich/hydrolysis cascade reaction of an indole derivative.

A highly efficient catalytic asymmetric dearomatization of naphthols by means of an electrophilic amination reaction catalyzed by chiral phosphoric acid is presented. This protocol provides a facile access to functionalized β-naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity (up to 99 % yield, up to 96 % ee).

The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98 % yield and 99 % ee.

The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]₂ (cod=1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

An intermolecular asymmetric dearomatization reaction of β-naphthols with nitroethylene through a chiral-thiourea-catalyzed Michael reaction is described. Enantioenriched functionalized β-naphthalenones with an all-carbon quaternary stereogenic center could thus be easily constructed from simple naphthol derivatives in good yields and excellent enantioselectivity (up to 79 % yield, 98 % ee).

Chiral hexahydropyrro[2,3]indole (HPI) units exist widely in natural and unnatural products with significant biological activities. The enantioselective synthesis of brominated hexahydropyrrolo[2,3-b]indole (HPI) subunits by asymmetric bromocyclization of tryptamine derivatives catalyzed by a chiral amine has been realized. In the presence of hydroquinine 1,4-phthalazinediyl diether ((DHQ)₂PHAL, 20 mol %) and L-(-)-camphorsulfonic acid (20 mol %), enantioenriched brominated HPI derivatives were obtained from readily available substituted tryptamines in up to 99% yield and 73% ee.

A Fe(OTf)₃ catalyzed [3+2] annulation reaction between 2,3-disubstituted indoles and N-Ts aziridines is described herein. A series of hexahydropyrrolo[3,4-b]indole derivatives bearing two consecutive quaternary carboncenters can be generated efficiently. The reaction features cheap catalyst, mild conditions and operational simplicity.

The first iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines and pyrazines has been realized. 2,3-Dihydroindolizine and 6,7-dihydropyrrolo[1,2-a]pyrazine derivatives were obtained with excellent yields and enantioselectivity. This methodology features dearomatization by direct N-allylic alkylation of pyridines or pyrazines under mild reaction conditions.

Highly efficient synthesis of enantiomerically enriched substituted piperidines has been realized via chiral phosphoric acid catalyzed cascade hydrogenative dearomatization of substituted pyridines and aza-Friedel-Crafts reaction in good to excellent yields and enantioselectivity.

Enantioselective construction of axially chiral biaryls by direct CH bond functionalization reactions has been realized. Novel axially chiral biaryls were synthesized by the direct CH bond olefination of biaryl compounds, using a chiral [Cp*Rh^III] catalyst, in good to excellent yields and enantioselectivities. The obtained axially chiral biaryls were found as suitable ligands for rhodium-catalyzed asymmetric conjugate additions.

Regio- and enantioselective synthesis of N-allylindoles was realized through an iridium-catalyzed asymmetric allylic amination reaction with 2-alkynylanilines and subsequent transition-metal-catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir-catalysis were treated with catalytic amount of NaAuCl₄⋅2 H₂O or PdCl₂ providing various substituted N-allylindoles in excellent yields and enantioselectivities.

Enantioselective construction of axially chiral biaryls by direct CH bond functionalization reactions has been realized. Novel axially chiral biaryls were synthesized by the direct CH bond olefination of biaryl compounds, using a chiral [Cp*Rh^III] catalyst, in good to excellent yields and enantioselectivities. The obtained axially chiral biaryls were found as suitable ligands for rhodium-catalyzed asymmetric conjugate additions.

Highly efficient synthesis of enantiomerically enriched substituted piperidines has been realized via chiral phosphoric acid catalyzed cascade hydrogenative dearomatization of substituted pyridines and aza-Friedel-Crafts reaction in good to excellent yields and enantioselectivity.

The first iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of pyridines and pyrazines has been realized. 2,3-Dihydroindolizine and 6,7-dihydropyrrolo[1,2-a]pyrazine derivatives were obtained with excellent yields and enantioselectivity. This methodology features dearomatization by direct N-allylic alkylation of pyridines or pyrazines under mild reaction conditions.

Copper-catalyzed C-2 arylation and vinylation of indole derivatives with iodonium salts have been realized. This method, featuring a simple operational procedure, mild reaction conditions, and a wide substrate scope, provided versatile indole derivatives with direct and selective functionalization at the C-2 position of the indole core. In the presence of excess amounts of iodonium salts, cascade C-2 arylation and dearomatization through the C-3 arylation reaction also proceeded smoothly.

A chemo- and regioselective iridium-catalyzed dienylation of ortho-aminostyrene derivatives with dienyl carbonates was realized. With a catalyst generated from [Ir(cod)Cl]₂ (2 mol %) and a racemic phosphoramidite ligand (4 mol %), 1Z,4E,6E-trienes were obtained in moderate to good yields with exclusive formation of a cis double bond.

Iridium-catalyzed asymmetric etherifications of allylic carbonates with 2-vinylphenols and 2-allylphenols were realized. With a catalyst generated from 2 mol% of [Ir(cod)Cl]₂ (cod=cycloocta-1,5-diene) and 4 mol% of the phosphoramidite ligand L2, the etherification products were obtained in excellent ees and then subjected to the ring-closing metathesis reaction providing an efficient synthesis of enantioenriched 2H-chromene and 2,5-dihydrobenzo[b]oxepine derivatives.

Highly enantioselective allylic alkylation reactions of methyl 2-(4-nitrophenylsulfonyl)acetate were carried out in the presence of an iridium catalytic system. The subsequent transformations of the products including reductive desulfonylation and modified Julia olefination led to the allylic alkylation products of methyl acetate or methyl acrylate with good yields and high enantioselectivity.

Chiral N-triflyl phosphoramide was found an efficient catalyst for the enantioselective Friedel-Crafts alkylation reaction of 4,7-dihydroindole with β,γ-unsaturated α-keto esters. In the presence of 5 mol% of the optimized catalyst, various pyrrolo[1,2-a]indoles were obtained in excellent enantioselectivity, moderate yields and up to 3:1 diastereoselectivity based on the one-pot synthesis including the Friedel-Crafts alkylation reaction and the subsequent p-benzoquinone oxidation.

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.