Search

Strategies that fully convert available racemic substrates into valuable enantioenriched products are urgently needed in organic synthesis. Reported herein is the first parallel kinetic asymmetric transformation of racemic cyclohexadienones. Racemic cyclohexadienones are first diastereoselectively converted into a new pair of racemic transient dienol intermediates, which are then parallel protonated by chiral phosphoric acid to deliver two sets of hydroindole products bearing a quaternary stereocenter with generally excellent enantioselectivity.

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C 2 - or C 1 -symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies., (© 2024. The Author(s).)

Base-catalyzed diastereodivergent and regioselective domino processes of triketone enones with arylacetaldehydes for the synthesis of tetrahydrofuro[2,3- b ]furans with four consecutive stereocenters are reported. Good yields and diastereoselectivities are obtained when DBU is employed as a catalyst; in contrast, Et 3 N delivers a different diastereomer in excellent diastereoselectivity. This work offers many advantages, including switchable diastereoselectivity, cheap base catalysts, and a simple operation.

Herein, the first diversity-oriented catalytic asymmetric dearomatization of indoles with o-quinone diimides (o-QDIs) is reported. The catalytic asymmetric dearomatization (CADA) of indoles is one of the research focuses in terms of the structural and biological importance of dearomatized indole derivatives. Although great achievements have been made in target-oriented CADA reactions, diversity-oriented CADA reactions are regarded as more challenging and remain elusive due to the lack of synthons featuring multiple reaction sites and the difficulty in precise control of chemo-, regio-, and enantio-selectivity. In this work, o-QDIs are employed as a versatile building block, enabling the chemo-divergent dearomative arylation and [4 + 2] cycloaddition reactions of indoles. Under the catalysis of chiral phosphoric acid and mild conditions, various indolenines, furoindolines/pyrroloindolines, and six-membered-ring fused indolines are collectively prepared in good yields with excellent enantioselectivities. This diversity-oriented synthesis protocol enriches the o-quinone chemistry and offers new opportunities for CADA reactions., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Reported herein is a highly efficient dynamic kinetic resolution protocol for the atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes. Atropisomers bearing vicinal diaxes mainly exist in o -triaryls, while that of biaryls is highly challenging in terms of the concerted rotation and deplanarization effects. The combination of C-C biaryl with N-N nonbiaryl delivers a novel class of vicinal-diaxis heterobiaryls. For their atroposelective synthesis, the dynamic kinetic resolution enabled by either quinine-catalyzed allylation or isothiourea-catalyzed acylation has been developed, allowing the preparation of a wide range of vicinal-axis heterobiaryls in good yields with excellent enantioselectivities. Atropisomerization experiments revealed that the C-C bond rotation led to diastereomers, and the N-N bond rotation offered enantiomers. Besides, this protocol could be extended to kinetic resolution by employing substrates with a more hindered axis., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

The success in the identification of the two enantioisomeric surfaces of electrophiles by dinuclear zinc catalysts is disclosed. This protocol realizes a dinuclear zinc-cocatalyzed desymmetrization of cyclopentendiones using α-hydroxy aryl ketones as nucleophiles through Michael addition reaction. Under mild conditions, a series of functional cyclopentanediones bearing multiple stereogenic centers including an all-carbon quaternary stereocenter, were obtained in moderate to good yields with excellent stereoselectivities., (© 2023 Wiley-VCH GmbH.)

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers., (© 2023. Springer Nature Limited.)

Reported herein is the catalytic asymmetric aminative dearomatization reaction of common phenols. As opposed to the well-studied indoles and naphthols, phenols are supposed to be challenging substrates for catalytic asymmetric dearomatization reactions in terms of their strong aromaticity and regioselectivity issues. Under the catalysis of a chiral phosphoric acid, the C4-regiospecific aminative dearomatization of phenols with azodicarboxylates readily occurred at ambient temperature, delivering an array of biologically and synthetically important aza-quaternary carbon cyclohexadieneones in good yields and with excellent enantioselectivities (29 examples, up to 98% yield, and >99% ee).

The first catalytic asymmetric interrupted Attanasi reaction has been established. Under the catalysis of a bifunctional organocatalyst, the condensation of cyclic β-keto esters with azoalkenes readily occurred, delivering a variety of bicyclic fused 2,3-dihydropyrroles with vicinal quaternary stereogenic centers in good yields and with good to excellent enantioselectivities (27 examples, up to 96% yield and 95% ee).

The first Zn-ProPhenol catalyzed asymmetric inverse-electron-demand Diels-Alder reaction has been accomplished. This protocol was carried out by a dual-activation mode under mild conditions, allowing the preparation of various biologically important dihydropyrans in good yields with excellent stereoselectivities.

The chiral phosphoric acid-catalyzed asymmetric intermolecular formal [3+2] cycloaddition of azoalkenes with azlactones has been established. This convergent protocol leads to a facile and enantioselective de novo construction of a wide range of fully substituted 4-pyrrolin-2-ones bearing a fully substituted carbon atom in good yields and with excellent enantioselectivities (26 examples, 72-95% yields and 87-99% ee).

We described herein a neoteric enantioselective cascade Michael/acyl transfer reaction of enynones and α-hydroxy aryl ketones catalyzed by dinuclear zinc cooperative catalysis. A series of structurally diverse chiral 1,5-dicarbonyl compounds were synthesized in good yields with excellent stereoselectivities. This strategy features broad substrate scope, high atom economy, as well as enynones as efficient electrophilic acyl transfer reagents in asymmetric cascade reactions for the first time.

The Sc(III)-catalyzed [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes has been established. Owing to the absence of a carbenoid intermediate, this protocol represents the first non-carbenoid variant of the Doyle-Kirmse reaction. Under mild conditions, a variety of tertiary thioethers have been readily prepared in good to excellent yields.

With a dinuclear zinc-ProPhenol complex as a catalyst, an efficient and novel [3 + 3] annulation of indoline-2-thiones and isatylidene malononitriles has been successfully developed via the Brønsted base and Lewis acid cooperative activation model. This practical methodology gives access to a broad range of chiral spiro[indoline-3,4'-thiopyrano[2,3- b ]indole] derivatives in good yields with excellent levels of enantioselectivities (up to 88% yield and 99% ee).

Axially chiral biaryl diols have achieved great success in asymmetric catalysis. By contrast, axially chiral biaryl amino alcohols are far less developed. Herein, we have rationally designed a versatile C 1 -symmetric biaryl amino alcohol scaffold 1-(1-amino-pyrrol-2-yl)naphthalen-2-ol (NPNOL) on the basis of axially chiral C2-arylpyrrole framework. For its enantioselective synthesis, the chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and azoalkenes had been established. By using this practical method, a wide range of NPNOLs were readily prepared in high yields and excellent atroposelectivities (38 examples, up to 89 % yield and 99 % ee). DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity. The easy transformations of NPNOL-derived products into organocatalysts/ligands and their preliminary applications in asymmetric catalytic reactions demonstrated the promising utility of NPNOL., (© 2022 Wiley-VCH GmbH.)

A facile chiral phosphoric-acid catalyzed asymmetric inverse-electron-demand aza-Diels-Alder reaction of 1,3-diazadienes with 3-vinylindoles was established. By using this mild and practical protocol, a broad range of benzothiazolopyrimidines with three contiguous stereogenic centers were prepared in good yields and excellent diastereo- and enantio-selectivities (43 examples, up to 83% yield, >99% ee and all >20 : 1 dr). A plausible concerted reaction pathway enabled by the dual hydrogen-bonding effect was proposed to account for the observed excellent enantioselectivity and specific trans - trans diastereoselectivity.

The umpolung activity of hemiacetals serving as α-carbon nucleophiles has been reported via dinuclear zinc cooperative catalysis. This umpolung strategy has been applied to catalytic asymmetric tandem reactions of 1-tosylindoline-2,3-diols with β,γ-unsaturated-α-keto compounds, providing a broad series of structurally diverse tetrahydrofuran spirooxindoles and dihydrofurans, respectively. In addition, products could be transformed to quinazoline and quinoline derivatives.

β,γ -Unsaturated α -ketoesters prove to be versatile organic synthons participating in diverse catalytic asymmetric transformations with the breathtaking development of organo-catalysis, new catalytic systems including ingenious chiral ligands as well as Lewis acid cations. The highly efficient creation of stereogenic centers with excellent enantioselectivity is not a surprise, but owes to the bidentate coordination of its unique 1,2-dicarbonyl motif to artful chiral messenger, establishing a rigid system for the precise chiral-identification of the attack. In the past five years, various reaction modes of β,γ -unsaturated α -ketoesters have been developed, involving their multiple reaction sites, such as the carbon-carbon double bond (C=C), the carbonyl group (C=O), the entire C=C-C=O fragment, and the ester group. In this review, we summarize the state-of-the-art catalytic asymmetric reactions of β,γ -unsaturated α -ketoesters, to provide an updated overview to chemists working in this and related fields, facilitating their discoveries in asymmetric catalysis, natural products synthesis, and drug development., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The first Brønsted acid-catalyzed oxa-Michael reaction cascade of 2-indolylmethanols with trione alkenes was accomplished. By using this practical approach, a variety of tetracyclic indoles were readily created in an ordered sequence with excellent regio- and diastereoselectivity. 2-Indolylmethanols commendably served as four-atom synthons, as opposed to the common three-atom synthons in the previous literature reports. The regioselectivity issue was well handled by the employment of a strong Brønsted acid catalyst. In addition, its dual role in activation of substrates via hydrogen-bonding interaction and acceleration of subsequent intramolecular cyclization and dehydration was proposed to account for the high reaction efficiency.

Pyrroloindolines are important and privileged polycyclic indoline motifs that are widely present in natural products and bio-significant molecules. From an organic chemistry perspective, their rigid tricyclic molecular architectures with a fully substituted carbon center at the C3a-position pose a great challenge to synthetic chemists. In a biological context, pyrroloindoline-containing alkaloids display a plethora of promising activities, making them significant in biological sciences and drug development. In the past few decades, pyrroloindoline and its analogues have emerged as appealing synthetic targets, attracting tremendous attention from the synthetic community. In this review, we summarize the state-of-the-art catalytic asymmetric synthesis of pyrroloindolines, as well as the related applications to the total synthesis of natural products.

The asymmetric allylic alkylation (AAA) of achiral Morita-Baylis-Hillman (MBH) carbonates with 3,3'-bisindolines under the catalysis of amino-acid-derived bifunctional phosphines was accomplished. With the AAA approach introduced herein, challenging 3,3'-bisindolines bearing an all-carbon quaternary stereocenter (C3a) have been constructed in good yields with good to excellent enantioselectivties. In addition, the synthetic value of this protocol was demonstrated by the facile synthesis of the core skeleton of gliocladin C.

An enantioselective umpolung γ-addition reaction of 3'-indolyl-3-oxindoles to allenoates catalyzed by amino acid-derived bifunctional phosphine catalysts has been developed. A wide range of chiral mixed 3,3'-bisindole scaffolds containing an all-carbon quaternary stereogenic center were obtained in high yields and with excellent enantioselectivities. 3,3'-Bisindoles are valuable synthetic intermediates, the employment of which led to formal total syntheses of (+)-Chimonanthine, (+)-Folicanthine and (-)-Calycanthine, as well as facile creation of useful pyrrolidinoindoline core structure., (Copyright © 2020 Science China Press. Published by Elsevier B.V. All rights reserved.)

Chiral phosphoric acid-catalyzed highly enantioselective formal [3 + 2] cycloaddition reaction of azoalkenes with 3-vinylindoles has been established. Under mild conditions, the projected cycloaddition proceeded smoothly, affording a variety of 2,3-dihydropyrroles in high yields and excellent enantioselectivities, and also in a diastereospecific manner. As opposed to the common 4-atom synthons in the previous literature reports, azoalkenes served as 3-atom synthons. Besides, the observed selectivity was supported by primary theoretical calculation. The unique chemistry of azoalkenes disclosed herein will empower asymmetric synthesis of nitrogen-containing ring structural motifs in a broader context., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The enantioselective dearomatization of indoles by an organocatalytic (3+2) reaction has been established. The reaction makes use of simple indole derivatives as substrates, and employs azoalkenes reaction partners. A wide range of pyrroloindolines containing an all-carbon quaternary stereogenic center were readily prepared in high yields and with excellent enantioselectivities., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A catalytic asymmetric conjugate addition of indoles to o-hydroxyphenyl substituted p-quinone methides has been established in the presence of chiral phosphoric acid, which afforded chiral indole-containing triarylmethanes in generally high yields (54-98%) and good enantioselectivities (90:10-96:4 enantiomeric ratio). The control experiments indicated that o-hydroxyphenyl substituted p-quinone methides had a high possibility to transform into o-quinone methides in the presence of chiral phosphoric acid, and the formation of o-quinone methides might be a necessity for the reaction. This reaction will not only contribute to the research field of catalytic asymmetric transformations of p-quinone methides and o-quinone methides but also provide a useful method for the construction of enantioenriched triarylmethane frameworks.

Construction of contiguous all-carbon quaternary stereogenic centers is a long-standing challenge in synthetic organic chemistry. In this report, a phosphine-catalyzed enantioselective (3+2) annulation reaction between allenes and isoindigos, containing either two identical or different oxindole moieties, is introduced as a powerful strategy for the construction of spirocyclic bisindoline alkaloid core structures. The reported reactions feature high chemical yields, excellent enantioselectivities, and very good regioselectivities, and are highly useful for creating structurally challenging bisindoline natural products., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A phosphine-catalyzed regiospecific (3 + 2) cyclization of 3-nitroindoles with allene esters has been established, which constructed indole-fused five-membered rings in good yields (up to 86%). This reaction serves as a powerful method for the construction of indole-fused five-membered rings. In addition, this reaction provides a useful strategy toward settling the challenge of utilizing other 1,3-dipoles or 1,3-dipole surrogates to perform (3 + 2) cyclizations with 3-nitroindoles in different catalytic modes, which will enrich the chemistry of nitroindoles and catalytic asymmetric dearomatization cyclizations.

A chiral guanidine-catalyzed asymmetric [4 + 1] cyclization of benzofuran-derived azadienes with 3-chlorooxindoles has been established, which constructed chiral spirooxindole frameworks with in situ generation of a five-membered ring with high diastereoselectivities (up to >95:5 dr) and good enantioselectivities (up to 94:6 er). This reaction represents the first catalytic asymmetric [4 + 1] cyclization of benzofuran-derived azadienes, which will enrich the research field of catalytic asymmetric cyclizations of such reactants. In addition, this reaction provides a useful strategy for the enantioselective construction of five-membered ring-based chiral spirooxindole scaffolds.

The first catalytic asymmetric construction of 3,3'-bisindole skeletons bearing both axial and central chirality has been established by organocatalytic asymmetric addition reactions of 2-substituted 3,3'-bisindoles with 3-indolylmethanols (up to 98 % yield, all >95:5 d.r., >99 % ee). This reaction also represents the first highly enantioselective construction of axially chiral 3,3'-bisindole skeletons, and utilizes the strategy of introducing a bulky group to the ortho-position of prochiral 3,3'-bisindoles. This reaction not only provides a good example for simultaneously controlling axial and central chirality in one operation, but also serves as a new strategy for catalytic enantioselective construction of axially chiral 3,3'-bisindole backbones from prochiral substrates., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The first [4 + 2] cyclization of para-quinone methide (p-QM) derivatives with allenes has been established via phosphine catalysis, which afforded a series of chroman derivatives in high yields (up to 97%) and excellent (E/Z)-selectivities (all >95 : 5 E/Z). This reaction will not only enrich the research contents of cyclization reactions involving p-QM derivatives, but also provide a good example of the application of allenes and phosphine catalysis in cyclization reactions. In addition, this approach also offers a useful method for the construction of chroman scaffolds.

A Brønsted acid-catalyzed (4 + 3) cyclization of N, N'-cyclic azomethine imines with isatoic anhydrides has been discovered, which constructs seven-membered nitrogenous heterocyclic frameworks with overall high yields (up to 98% yield). This reaction represents a rarely reported (4 + 3) cyclization of N, N'-cyclic azomethine imines, which involves the reassembly of a C-N bond. In addition, this reaction has also accomplished the unprecedented (4 + 3) cyclization of isatoic anhydrides.

Under cooperative catalysis of iridium and a Brønsted acid, different C4-substituted azlactones react with vinyl benzoxazinones via a formal [4+2] cycloaddition or substitution reaction in a chemo- and stereoselective mode. Furthermore, the catalytic asymmetric version of the formal [4+2] cycloaddition established cooperative catalysis of iridium and a chiral thiourea-tertiary amine.

The first de novo construction of enantioenriched dihydroquinazolinones via an intermolecular strategy has been established. This approach also represents the first catalytic asymmetric [4+2] cycloaddition of vinyl benzoxazinanones with sulfonyl isocyanates, which afforded chiral dihydroquinazolinones in high yields and excellent enantioselectivities (up to 98% yield, 99 : 1 er). This reaction not only confronts the great challenge in de novo construction of enantioenriched dihydroquinazolinone skeletons, but also advances the chemistry of decarboxylative cycloadditions involving vinyl benzoxazinanones.

An oxa-[4+2] cyclization of quinone methides with alkynyl benzyl alcohols has been realized in the presence of a metal catalyst, and the reaction afforded spiroacetal products in overall high yields (up to 99%) and good diastereoselectivities (up to >95:5 dr). By carrying out the reaction under gold catalysis and utilizing alkynyl benzyl alcohols as electron-rich reaction partners, this approach provides a useful strategy for settling the challenges in oxa-[4+2] cyclization of para-quinone methide derivatives. This reaction serves as a good example for metal-catalyzed oxa-[4+2] cyclizations of quinone methides. In addition, it also offers a useful method for the construction of spiroacetal skeletons.

The first [4 + 2] cyclization/retro-Mannich reaction cascade of para-quinone methides with Pd-containing 1,4-dipoles generated in situ from vinyl benzoxazinanones has been established. The corresponding rearrangement products were obtained in generally good to excellent yields (up to 92% yield). This reaction represents the first example of C[double bond, length as m-dash]C double bond cleavage of para-quinone methides, which will greatly enrich the chemistry of quinone methides.

An organocatalytic [4 + 1] cyclization of o-QMs with MBH carbonates has been established using naphthylindole-derived phosphine (NIP) as an organocatalyst. By using this approach, a series of 2,3-dihydrobenzofuran derivatives have been synthesized in high yields and excellent diastereoselectivities (up to 99% yield, >95:5 dr). This reaction not only has established the first [4 + 1] cyclization of o-QMs with MBH carbonates but also represents the first application of naphthylindole-derived phosphines as organocatalysts in catalytic reactions. In addition, this reaction has also provided a useful method for constructing 2,3-dihydrobenzofuran scaffolds.

A synergistic-catalysis-enabled reaction of 2-indolymethanols with oxonium ylides has been established that makes use of a three-component reaction between 3-diazooxindoles, alcohols, and 2-indolymethanols under the cooperative catalysis of a metal complex and a Brønsted acid. This reaction has not only provided a new approach for the construction of 3-indolyl-3-alkoxy oxindole scaffolds by utilizing the C3-electrophilicity of an indole, but it is also the first example of a nucleophilic addition of a metal-associated ylide to 2-indolylmethanols. In addition, this reaction also includes a rarely reported trapping of onium ylides with aryl electrophiles., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The first catalytic asymmetric construction of chiral dihydrobenzo[ e]indole scaffolds has been established in a highly diastereo- and enantioselective mode (30 examples, up to 99% yield, >95:5 dr, >99% ee), which makes use of chiral phosphoric acid-catalyzed [3 + 2] cycloannulations of azonaphthalene derivatives with 3-vinylindoles. This reaction also represents the first catalytic asymmetric cycloannulation of azonaphthalene derivatives with alkenes, which will not only provide a useful method for constructing enantioenriched dihydrobenzo[ e]indole scaffolds but also advance the chemistry of catalytic asymmetric reactions of azonaphthalene derivatives.

A chiral phosphoric acid-catalyzed asymmetric interrupted Nazarov-type cyclization of C3-alkenyl-substituted 2-indolylmethanols has been established by using cyclic enaminones as nucleophiles, which afforded chiral cyclopenta[b]indole derivatives with excellent diastereoselectivities and moderate to good enantioselectivities. This reaction will not only enrich the research contents of indolylmethanol-involved catalytic asymmetric transformations, but also advance the chemistry of catalytic asymmetric interrupted Nazarov-type cyclizations. In addition, this reaction will also provide a useful method for synthesizing chiral cyclopenta[b]indole derivatives.

Chiral spirooxindoles are privileged heterocyclic motifs, which are widely found in natural alkaloids and pharmaceuticals. Moreover, the construction of chiral spiro-cyclic frameworks is a long-lasting challenge in organic synthesis. The past four years have witnessed significant developments in this field, and this feature article outlines the recent progress in the catalytic asymmetric synthesis of spirooxindoles, including the contributions of our group. The catalytic asymmetric construction of spirooxindoles has greatly benefited from the utilization of oxindole derivatives as starting materials, including isatin derivatives, methyleneindolinones, indolin-2-one derivatives and isatin-derived 3-indolylmethanols. This article is divided into sections according to the size and type of the generated spiro-ring fused at the C3-position of the oxindole core (from three-membered to seven-membered spiro-rings), and representative examples are given with illustrations. In addition, the enantioselective construction of bispirooxindole frameworks is also discussed in the last section.

A chemodivergent reaction of 2-indolylmethanols with tryptophols has been established via an interrupted Nazarov-type cyclization in the presence of Brønsted acid, leading to the efficient synthesis of two series of cyclopenta[ b]indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It was found that the presence or absence of molecular sieves played an important role in controlling the chemoselectivity of the reaction. In the presence of 3 Å molecular sieves, tryptophol would utilize the nucleophilicity of its nitrogen atom to form a new C-N bond, while, in the absence of molecular sieves, tryptophol would utilize the nucleophilicity of its C2-position to generate a new C-C bond. Therefore, this reaction will provide a good example for additive-controlled chemoselectivity. In addition, this approach not only provides a useful strategy for the synthesis of structurally diversified cyclopenta[ b]indoles but also demonstrates the practicability of 2-indolylmethanols in organic synthesis.

The first catalytic asymmetric [2+3] cyclization of azlactones with azonaphthalenes has been established. This strategy allowed the synthesis of a variety of chiral isatin derivatives in generally good yields and excellent enantioselectivities (up to 99 % yield, 98 % ee). The developed reaction has not only established a catalytic enantioselective [2+3] cyclization using azlactones as two-carbon building blocks, but also enriches the chemistry of catalytic asymmetric cyclizations of azonaphthalenes. In addition, this protocol will provide a useful method for constructing enantioenriched 3,3'-disubstituted isatin-type frameworks., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A catalytic asymmetric α-arylation of aldehydes using 2-indolylmethanols as arylation reagents has been established. This reaction was enabled by a cooperative catalytic system consisting of a gold complex, a Brønsted acid, and a chiral amine, which have a synergistic effect in the reaction process. By using this strategy, a series of α-arylation products of aldehydes were generated in overall acceptable yields and good enantioselectivities (up to 69%, 91:9 er). The control experiments demonstrated that the addition of PPh 3 AuCl as a gold complex was helpful to improve the yield, and trifluoroacetic acid as a Brønsted acid played a crucial role in the reaction by promoting the generation of carbocation and chiral enamine intermediates, which are two key intermediates of the asymmetric α-arylation reaction. In addition, the enantioselectivity of the reaction was mainly controlled by the chiral amine catalyst via forming a chiral enamine intermediate. This reaction has not only provided a useful protocol for catalytic asymmetric α-arylation of aldehydes but also enriched the research contents of 2-indolylmethanol-involved reactions and asymmetric cooperative catalysis.

A Brønsted acid-catalyzed direct C3-arylation of 2-indolylmethanols with tryptamines and tryptophols has been established, leading to a series of potentially bioactive 2,3'-biindole derivatives with a broad substrate scope and generally good yields (38 examples, up to 96% yield). In this process, the reactivity of the C3-position of 2-indolylmethanol is switched from nucleophilic to electrophilic, which can serve as an umpolung strategy in indole chemistry. This protocol not only provides a new strategy for accessing structurally diversified 2,3'-biindolyl frameworks, but also satisfies the requirement of green chemistry.

The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3-nitroindoles with vinylcyclopropanes has been established, which constructed chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities (up to 97% ee). This reaction also represents the first application of all-carbon 1,3-dipoles in catalytic asymmetric dearomative [3 + 2] cycloadditions of 3-nitroindoles. This approach will not only advance the catalytic asymmetric dearomatization reactions of electron-deficient indoles but also provide an efficient method for constructing chiral cyclopenta[b]indoline scaffolds.

The first cyclization of para-quinone methide derivatives with alkynes was established by utilizing the [4 + 2] reaction of ortho-hydroxyphenyl-substituted para-quinone methides with ynones or benzyne, which efficiently constructed the scaffolds of chromene and xanthene in high yields (up to 88%). This protocol has not only fulfilled the task of developing cyclization reactions of para-quinone methide derivatives but also provided an efficient method for constructing chromene and xanthene scaffolds.

A catalytic asymmetric [4+2] cycloaddition of ortho-quinone methide imines in situ generated from o-aminobenzyl alcohols with o-hydroxystyrenes has been established under the catalysis of chiral phosphoramide, which afforded chiral tetrahydroquinolines in moderate to good yields, good enantioselectivities, and excellent diastereoselectivities (up to 82% yield, 93:7 er, all >95:5 dr). In this catalytic asymmetric [4+2] cycloaddition, the hydrogen-bonding interaction between chiral phosphoramide and two substrates was proposed to play a crucial role in controlling the enantioselectivity. This reaction not only provides a useful approach for constructing chiral tetrahydroquinoline frameworks, but also demonstrates the great practicability of ortho-quinone methide imines in catalytic asymmetric cycloadditions.

The first catalytic asymmetric arylative dearomatization of tryptophols has been established. By using quinone imine ketals as aryl group surrogates and modulating the reaction conditions, the cascade reaction of tryptophols with quinone imine ketals in the presence of chiral phosphoric acid afforded two series of arylative dearomatization products with generally high yields (up to 99%), and excellent diastereo- and enantioselectivities (all > 95 : 5 dr, 90% to 99% ee) in a chemoselective manner.

A catalytic asymmetric decarboxylative [4+2] cycloaddition of vinyl benzoxazinanones with methyleneindolinones has been established, which provided a series of chiral tetrahydroquinoline-based 3,3'-spirooxindoles in high yields (up to 96%) and with excellent diastereo- and enantioselectivities (all >95 : 5 d.r., up to 99% ee). This reaction not only represents the first example of catalytic enantioselective [4+2] cycloaddition between methyleneindolinones and Pd-containing 1,4-dipoles, but also demonstrates the great practicability of catalytic asymmetric decarboxylative cycloadditions in the synthesis of enantio-enriched polycyclic compounds.

Indolylmethanols have emerged as versatile reactants in catalytic asymmetric reactions because of the facile generation of reactive intermediates from these compounds. The most common indolylmethanols are 3-indolylmethanols and 2-indolylmethanols, and the reaction types applicable to these heterocycles mainly include catalytic enantioselective substitutions and cyclizations. Using indolylmethanols as reactants in catalytic asymmetric reactions enables the enantioselective construction of a variety of indole-containing frameworks.