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

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, Et3N 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. 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.

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. 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.

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).

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.

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

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 ß,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.

Dinuclear Zinc Catalyzed Enantioselective Dearomatization [3+2] Annulation of 2-Nitrobenzofurans and 2-Nitrobenzothiophenes.

The application of dinuclear zinc catalysts in a dearomatization reaction has been developed. Catalytic asymmetric dearomatization [3+2] annulations of 2-nitrobenzofurans or 2-nitrobenzothiophenes with CF3 -containing N-unprotected isatin-derived azomethine ylides catalyzed by dinuclear zinc catalysts are realized with excellent diastereomer ratios (dr) of >20 : 1 and enantiomeric excess (ee) of up to 99 %. This protocol provides a practical, straightforward access to structurally diverse pyrrolidinyl spirooxindoles containing a 2,3-fused-dihydrobenzofuran (or dihydrobenzothiphene) moiety, and four contiguous stereocenters. Reactions can be performed on a gram scale. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.

Dinuclear zinc-catalyzed asymmetric Friedel-Crafts alkylation/cyclization of 3-aminophenols with α,α-dicyanoolefins.

An enantioselective Friedel-Crafts alkylation/cyclization tandem reaction of 3-aminophenols with α,α-dicyanoolefins has been performed successfully using a chiral dinuclear zinc catalyst, leading to a range of chiral 2-amino-4H-chromenes (up to 98% yield and >99% ee). To the best of our knowledge, this is the first asymmetric example of the dinuclear zinc-catalysed functionalization of aromatic C(sp2)-H bonds.

Dinuclear zinc-catalyzed enantioselective formal [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with low reactivity aurone derivatives.

Highly enantioselective formal [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with aurone derivatives of low reactivity using chiral dinuclear zinc catalysts has been developed via a Brønsted base and Lewis acid cooperative activation model. These transformations involving a domino Michael/Mannich reaction sequence led to efficient construction of a range of chiral spiro[benzofuran-pyrrolidine] scaffolds bearing three biologically relevant heterocyclic moieties and two adjacent spiro quaternary stereocenters in high yields (up to 95%) and with good enantioselectivities (up to 99% ee).

Direct Asymmetric α-Selective Mannich Reaction of ß,γ-Unsaturated Ketones with Cyclic α-Imino Ester: Divergent Synthesis of Cyclocanaline and Tetrahydro Pyridazinone Derivatives.

The first regio-, diastereo-, and enantioselective direct Mannich reaction of ß,γ,-unsaturated ketones with benzoxazinone cyclic imines was enabled by Lewis acid/Brønsted base cooperative catalysis. The dinuclear zinc complex catalyzed the reaction of a broad range of ß,γ-unsaturated ketones to proceed at the α-site exclusively, leading to corresponding adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90-99 % ee range. These products were used as general intermediates in the synthesis of multisubstituted cyclocanalines, tetrahydro pyridazinones, and 4H-furo[2,3-b][1,4]benzoxazine derivatives.

Brønsted Acid Catalyzed Enantioselective Assembly of Spirochroman-3,3-oxindoles.

An enantioselective cyclization of diazoindolinones with o-hydroxymethyl chalcones has been established by a cooperative dirhodium complex and chiral phosphonic acid catalysis under mild conditions. This reaction is the first example of catalytic asymmetric intramolecular Michael-type trapping of oxonium ylide enabled by phosphoric acid through a dual H-bonding activation model, which provides an efficient access to the chiral spirochroman-3,3-oxindoles, with vicinal quaternary and tertiary stereocenters, in good to excellent yields and enantioselectivities.

A Rh(ii)-catalyzed three-component reaction of 3-diazooxindoles with N,N-disubstituted anilines and glyoxylates for the synthesis of 3-aryl-3-substituted oxindoles.

A simple and effective method for the synthesis of 3-aryl-3-substituted oxindole derivatives via a [Rh]-catalyzed three-component reaction of 3-diazooxindoles with N,N-disubstituted anilines and glyoxylates is developed. This transformation is proposed to proceed through an intermolecular aldol-type trapping of zwitterionic intermediates.