Divergent Synthesis of Chiroptical Molecular Switches Based on 1,2-Diaxial Atropisomers.

The development of chiroptical molecular switches for chiral sensing, data communication, optical displays, chiral logic gates, and asymmetric catalysis is currently a vibrant frontier of science and technology. Herein, we report a practical artificial dynamic system based on a 1,2-diaxial atropisomer. Organocatalytic parallel kinetic resolution allows the divergent synthesis of two sets of stereoisomers with vicinal C-C and N-N axes from the same racemic single-axis substrates.

A Chemically Powered Rotary Molecular Motor Based on Reversible Oxazepine Formation.

While biological machines are powered mainly by chemical transformations, chemically driven artificial rotary motor systems are very limited. Here, we report an aniline-phenol-based rotary molecular motor that operates via an information ratchet mechanism. The 360° directional rotation about a single covalent bond can be chemically driven by reversible oxazepine formation.

Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations.

Enantioenriched unsymmetrical vicinal diamines are important basic structural motifs. While catalytic asymmetric intermolecular 1,2-diamination of carbon-carbon double bonds represents the most straightforward approach for preparing enantioenriched vicinal-diamine-containing heterocycles, these reactions are often limited to the installation of undifferentiated amino functionalities through metal catalysis and/or the use of stoichiometric amounts of oxidants. Here, we report organocatalytic enantioselective unsymmetrical 1,2-diaminations based on the rational design of a bifunctional 1,2-diamination reagent, namely, azocarboxamides (ACAs).

Enantiodivergent Cyclization of Racemic Cyclohexadienones via Parallel Kinetic Asymmetric Transformation.

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.

Catalytic asymmetric synthesis of planar-chiral dianthranilides via (Dynamic) kinetic resolution.

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.

Diastereodivergent and Regioselective Synthesis of Tetrahydrofuro[2,3-]furans with Four Consecutive Stereocenters.

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

Diversity-Oriented Catalytic Asymmetric Dearomatization of Indoles with o-Quinone Diimides.

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.

Catalytic atroposelective synthesis of heterobiaryls with vicinal C-C and N-N diaxes via dynamic kinetic resolution.

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 -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.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

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.

Dinuclear Zinc-Catalyzed Asymmetric Desymmetrization of Cyclopentendiones: Access to Functional Cyclopentanediones Bearing an All-carbon Quaternary Stereocenter.

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.

Catalytic Asymmetric Synthesis of Aza-Quaternary Carbon Cyclohexadieneones Enabled by Aminative Dearomatization of Phenols.

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).

Catalytic asymmetric interrupted Attanasi reaction: access to fused 2,3-dihydropyrroles with vicinal quaternary carbons.

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).

Zn-ProPhenol catalyzed asymmetric inverse-electron-demand Diels-Alder reaction.

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.

Catalytic asymmetric construction of 4-pyrrolin-2-ones intermolecular formal [3+2] cycloaddition of azoalkenes with azlactones.

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 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).

Zinc-Catalyzed Asymmetric Cascade Michael/Acyl Transfer Reaction between α-Hydroxy Aryl Ketones and Enynones.

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.

Catalytic [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes: non-carbenoid Doyle-Kirmse reaction.

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.

Zinc-Catalyzed Enantioselective [3 + 3] Annulation for Synthesis of Chiral Spiro[indoline-3,4'-thiopyrano[2,3-]indole] Derivatives.

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-]indole] derivatives in good yields with excellent levels of enantioselectivities (up to 88% yield and 99% ee).

The Rational Design and Atroposelective Synthesis of Axially Chiral C2-Arylpyrrole-Derived Amino Alcohols.

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 -symmetric biaryl amino alcohol scaffold 1-(1-amino-pyrrol-2-yl)naphthalen-2-ol (NPNOL) on the basis of axially chiral C2-arylpyrrole framework.

Catalytic asymmetric inverse-electron-demand aza-Diels-Alder reaction of 1,3-diazadienes with 3-vinylindoles.

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 - diastereoselectivity.

Catalytic Asymmetric Umpolung Tandem Reactions of Hemiacetals via Dinuclear Zinc Cooperative Catalysis.

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.

Further developments of -unsaturated -ketoesters as versatile synthons in asymmetric catalysis.

-Unsaturated -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 -unsaturated -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.

2-Indolymethanols as 4-atom-synthons in oxa-Michael reaction cascade: access to tetracyclic indoles.

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.

Catalytic asymmetric preparation of pyrroloindolines: strategies and applications to total synthesis.

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.

Phosphine-Catalyzed Asymmetric Allylic Alkylation of Achiral MBH Carbonates with 3,3'-Bisindolines: Enantioselective Construction of Quaternary Stereogenic Centers.

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.

Enantioselective synthesis of mixed 3,3'-bisindoles via a phosphine-catalyzed umpolung γ-addition of 3'-indolyl-3-oxindoles to allenoates.

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.