Dinuclear Zinc Catalyst Research Articles

Access to Tetrahydrothiopyrano[2,3‐b]Indole Derivatives via Zinc‐Catalyzed Asymmetric [3+3] Annulation of Indoline‐2‐Thiones with Yne–Enones

AbstractWe report herein an enantioselective [3+3] annulation of indoline‐2‐thiones with yne–enones by chiral dinuclear zinc catalysts via a Brønsted base and Lewis acid cooperative activation model. This transformation proceeded through sequential conjugate addition, allenyl ketone formation and intramolecular sulfa‐Michael 6‐endo‐trig cyclization. A range of enantioenriched tetrahydrothiopyrano[2,3‐b]indole derivatives bearing an exocyclic double bond were obtained in moderate yields with excellent stereoselectivities (up to 20 : 1 dr, 20:1 Z/E ratio and 95% ee). Late‐stage functionalization, large‐scale experiment and further derivatizations were also explored.

Dinuclear zinc catalysis of a kinetic resolution strategy for distinguishing one pair of diastereoisomers from multiple stereoisomers

A new kinetic resolution strategy of distinguishing four stereoisomers is realized by dinuclear zinc catalysts.

Dinuclear Zinc Catalyzed [3+2] Annulation of Benzylideneindolinones Access to CF3‐Containing 2,3‐Pyrrolidinyl Dispirooxindoles

AbstractThis report has realized the catalytic asymmetric [3+2] annulation of benzylideneindolinones with CF3‐containing isatin‐derived azomethine ylides for the first time, in which the organocatalysis has failed. In the presence of dinuclear zinc catalysts, a series of functionalized 2,3‐pyrrolidinyl dispirooxindoles have been synthesized in good yields with excellent stereoselectivity under mild reaction conditions. This protocol can be run on a gram scale and a possible catalytic mechanism is proposed.

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.

Diverse synthesis of α-tertiary amines and tertiary alcohols via desymmetric reduction of malonic esters

Amines and alcohols with a fully substituted α-carbon are structures of great value in organic synthesis and drug discovery. While conventional methods towards these motifs often rely on enantioselective carbon-carbon or carbon-heteroatom bond formation reactions, a desymmetric method is developed here by selectively hydrosilylating one of the esters of easily accessible α-substituted α-amino- and -oxymalonic esters. The desymmetrization is enabled by a suite of dinuclear zinc catalysts with pipecolinol-derived tetradentate ligands and can accommodate a diverse panel of heteroatom substituents, including secondary amides, tertiary amines, and ethers of different sizes. The polyfunctionalized reduction products, in return, have provided expeditious approaches to enantioenriched nitrogen- and oxygen-containing molecules, including dipeptides, vitamin analogs, and natural metabolites.

A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides.

Enantioenriched tertiary alkyl halides are prevalent in bioactive molecules and can serve as versatile synthetic intermediates to construct complex structures. While conventional access to these motifs often hinges on stereoselective carbon-halogen or carbon-carbon bond formation reactions, desymmetric approaches using halogenated and prochiral tetrasubstituted carbons are largely elusive in comparison. Here, we report that a suite of dinuclear zinc catalysts with a prolinol- or pipecolinol-derived tetradentate ligand can reductively desymmetrize a large collection of easily available halomalonic esters to α-halo-β-hydroxyesters. These polyfunctionalized tertiary alkyl fluorides, chlorides, and bromides proved to be useful intermediates toward fluorinated drug analogs and polyhalogenated monoterpenes. The facile intramolecular epoxidation of the chiral chloride and bromide products has also enabled expeditious access to natural products containing tertiary alcohol motifs.

A sustainable approach for the synthesis of recyclable cyclic CO2-based polycarbonates.

It is highly desirable to reduce the environmental pollution related to the disposal of end-of-life plastics. Polycarbonates derived from the copolymerization of CO2 and epoxides have attracted much attention since they can enable CO2-fixation and furnish biorenewable and degradable polymeric materials. So far, only linear CO2-based polycarbonates have been reported and typically degraded to cyclic carbonates. Here we synthesize a homogeneous dinuclear methyl zinc catalyst ((BDI-ZnMe)2, 1) to rapidly copolymerize meso-CHO and CO2 into poly(cyclohexene carbonate) (PCHC) with an unprecedentedly cyclic structure. Moreover, in the presence of trace amounts of water, a heterogeneous multi-nuclear zinc catalyst ((BDI-(ZnMe2·xH2O))n, 2) is prepared and shows up to 99% selectivity towards the degradation of PCHC back to meso-CHO and CO2. This strategy not only achieves the first case of cyclic CO2-based polycarbonate but also realizes the complete chemical recycling of PCHC back to its monomers, representing closed-loop recycling of CO2-based polycarbonates.

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.

Brønsted Base and Lewis Acid Cooperatively Catalyzed Asymmetric exo'-Selective [3 + 2] Cycloaddition of Trifluoromethylated Azomethine Ylides and Methyleneindolinones.

A Brønsted base and Lewis acid cooperatively catalyzed 1,3-dipolar cycloaddition is reported through chiral dinuclear zinc catalysts. An asymmetric exo'-selective [3 + 2] cycloaddition of CF3-containing N-unprotected isatin-derived azomethine ylides is realized. In the presence of 10 mol % of catalyst, azomethine ylides react efficiently with methyleneindolinones, giving a series of trifluoromethyl-substituted 2,3-pyrrolidinyl dispirooxindoles with highly enantio- (up to 99% ee) and exo'-selectivity (>20:1 dr). Up to four contiguous stereogenic centers, including two adjacent spiro quaternary stereocenters, are constructed in one step.

Catalytic Asymmetric Synthesis of Tetrahydrofuran Spirooxindoles via a Dinuclear Zinc Catalyst.

An asymmetric Michael/hemiketalization and Fridel-Crafts reaction has been reported through a one-pot reaction. A number of structurally novel tetrahydrofuran spirooxindoles are synthesized in the presence of a 10 mol % dinuclear zinc catalyst with diastereomer ratios (dr) of 3:1-13:1 and an enantiomeric excess (ee) of 75-99%. The reaction can be performed on a gram scale without impacting its efficiency. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.

Enantioselective synthesis of indanone spiro-isochromanone derivatives via a dinuclear zinc-catalyzed Michael/transesterification tandem reaction.

An enantioselective Michael/transesterification tandem reaction of α-hydroxy indanones with ortho-ester chalcones was realized using dinuclear zinc catalysts. A series of enantiomerically pure spiro[indanone-2,3'-isochromane-1-one] derivatives were obtained in good yields with excellent stereoselectivities (up to >20 : 1 dr, up to >99% ee). This protocol could be conducted on a gram scale without affecting its stereoselectivities. In addition, the absolute stereochemistry of the products was determined by X-ray crystallographic analysis of 3ac, and a positive nonlinear effect was observed. Finally, a possible catalytic cycle was proposed to explain the origin of the enantioselectivity.

Asymmetric Friedel-Crafts Alkylation of Indoles with Trifluoromethyl Pyruvate Catalyzed by a Dinuclear Zinc Catalyst.

A bimetallic cooperative catalysis model has been reported for the asymmetric Friedel-Crafts (F-C) alkylation of indoles with trifluoromethyl pyruvates using Trost's intramolecular dinuclear zinc complex as the catalyst. This dinuclear zinc catalyst was prepared in situ by reacting the chiral ligand (S,S)-L2b with 2 equiv of ZnEt2. A series of trifluoromethyl alcohol and indole-containing biological compounds were formed in moderate to good yields (up to 95%) with good enantioselectivity (up to 88% enantiomeric excess (ee)) in the presence of 10 mol % catalyst under mild conditions. A synergistic transition state model was proposed to explain the origin of the asymmetric induction.

Asymmetric Friedel-Crafts Alkylation of Pyrrole with Chalcones Catalyzed by a Dinuclear Zinc Catalyst

Asymmetric Friedel-Crafts Alkylation of Pyrrole with Chalcones Catalyzed by a Dinuclear Zinc Catalyst

Azetidine-derived dinuclear zinc catalyzed asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds.

The asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds by using an azetidine-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad spectrum of enones and α,β-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using additives. The products were obtained with more than 95% ee for 23 examples of α,β-unsaturated carbonyl compounds. A positive nonlinear effect was observed and the possible mechanism was proposed.

ChemInform Abstract: Chemistry of Pyruvate Enolates: anti‐Selective Direct Aldol Reactions of Pyruvate Ester with Sugar Aldehydes Promoted by a Dinuclear Zinc Catalyst.

ChemInform Abstract: Chemistry of Pyruvate Enolates: anti‐Selective Direct Aldol Reactions of Pyruvate Ester with Sugar Aldehydes Promoted by a Dinuclear Zinc Catalyst.

Sequence Selective Polymerization Catalysis: A New Route to ABA Block Copoly(ester-b-carbonate-b-ester)

The preparation of ABA type block copoly(ester-b-carbonate-b-ester) from a mixture of e-caprolactone, cyclohexene oxide, and carbon dioxide monomers and using a single catalyst is presented. By using a dinuclear zinc catalyst, both the ring-opening polymerization of e-caprolactone and the ring-opening copolymerization of cyclohexene oxide and carbon dioxide are achieved. The catalyst shows high selectivity, activity, and control in the ring-opening copolymerization, yielding poly(cyclohexene carbonate) polyols, i.e., α,ω-dihydroxyl end-capped polycarbonates. It also functions efficiently under immortal conditions, and in particular, the addition of various equivalents of water enables the selective preparation of polyols and control over the polymers’ molecular weights and dispersities. The catalyst is also active for the ring-opening polymerization of e-caprolactone but only in the presence of epoxide, generating α,ω-dihydroxyl-terminated polycaprolactones. It is also possible to combine the two polymeri...

Chemistry of Pyruvate Enolates: anti‐Selective Direct Aldol Reactions of Pyruvate Ester with Sugar Aldehydes Promoted by a Dinuclear Zinc Catalyst

AbstractA chiral dinuclear zinc complex can effectively catalyse the direct aldol reactions of pyruvic acid ester with various chiral sugar aldehydes, thus functionally mimicking the pyruvate‐dependent type II aldolases. Application of sterically hindered aryl esters allows for the elusive aldol reaction of the pyruvate donor with controlled anti‐selectivity en route to the short and efficient synthesis of 3‐deoxy‐2‐ulosonic acids. Pyruvic acid ester is here used as a chemical equivalent of phosphoenol pyruvate (PEP) in imitation of the synthetic principle used in nature. The presented biomimetic methodologies use enol formation for the highly efficient and flexible formation of various C6–C9 ulosonic acids. Particularly, efficient and concise syntheses of 3‐deoxy‐D‐erythro‐hex‐2‐ulosonic acid (KDG, overall 50% yield), 3‐deoxy‐D‐ribo‐hept‐2‐ulosonic acid (DRH, overall 53% yield) and 3‐deoxy‐D‐glycero‐D‐talo‐non‐2‐ulosonic acid (4‐epi‐KDN, overall 78% yield) are described. This direct efficient application of pyruvic esters does not require additional demasking steps and thus surpassess previously methodologies utilising masked pyruvic synthons such 2‐acetylthiazole and pyruvic aldehyde dimethyl acetal.magnified image

ChemInform Abstract: Enantioselective Friedel—Crafts Alkylation of Pyrrole with Chalcones Catalyzed by a Dinuclear Zinc Catalyst.

AbstractA novel chiral azetidine‐based ligand is synthesized and applied to a highly enantioselective Friedel—Crafts alkylation of pyrrole.

Mechanistic Aspects of a Highly Active Dinuclear Zinc Catalyst for the Co-polymerization of Epoxides and CO2.

The dinuclear zinc complex reported by us is to date the most active zinc catalyst for the co-polymerization of cyclohexene oxide (CHO) and carbon dioxide. However, co-polymerization experiments with propylene oxide (PO) and CO2 revealed surprisingly low conversions. Within this work, we focused on clarification of this behavior through experimental results and quantum chemical studies. The combination of both results indicated the formation of an energetically highly stable intermediate in the presence of propylene oxide and carbon dioxide. A similar species in the case of cyclohexene oxide/CO2 co-polymerization was not stable enough to deactivate the catalyst due to steric repulsion.

Asymmetric Copolymerization of Cyclopentene Oxide and CO2 Using a Dinuclear Zinc–AzePhenol Catalyst: Enlightened by DFT Calculations

Optically active polycarbonates (PCs) are considered as candidates for new and valuable materials because of their well-defined chemical structures and special physical properties. Previous studies on asymmetric alternating copolymerization of cyclopentene oxide (CPO) and CO2 regarding chiral zinc catalysts provided poly(cyclopentene carbonate) (PCPC) with moderate enantioselectivity, and thus, the development of highly efficient catalysts for this enantioselective polymerization is highly desirable. This research work is enlightened by the DFT calculations. In this paper, we clearly describe the use of intramolecular dinuclear zinc–AzePhenol complex as a high performance catalyst for the asymmetric copolymerization of CPO and CO2, affording completely alternating PCPC under very mild conditions (1 atm CO2, 30 °C) in 98% yield with >99% enantioselectivity for (S,S)-configuration. The dinuclear catalyst is prepared in situ from the reaction of multidentate semiazecrown ether ligand and ZnEt2, followed by treatment with an alcohol additive. In addition, our previous studies indicated that this catalyst also showed excellent enantioselectivity in the asymmetric copolymerization of cyclohexene oxide (CHO) and CO2. In order to obtain more information on the mechanism of the catalytic copolymerization, the chemical structures of PCPC are characterized by 1H NMR and 13C NMR spectroscopy, and the nonlinear effect is also investigated in this copolymerization. A plausible catalytic cycle for the present reaction system is outlined. The reaction of chiral ligand with ZnEt2, followed by the ethyl group exchange with EtOH, affords the ethoxy-bridged dinuclear zinc complex. The copolymerization reaction is initiated by the insertion of CO2 into the Zn–OEt bond to give a carbonate–ester-bridged complex. The two zinc centers are situated sufficiently close to each other to allow a synergistic effect in the copolymerization, meaning that one zinc atom acts as Lewis acid to activate the epoxide, the other is responsible for carbonate propagation through the nucleophilic attack of carbonate ester at the back side of the cis-epoxide by a six-membered transition state. Furthermore, the dinuclear zinc structure of the catalyst remains intact throughout the catalytic copolymerization. The proposed mechanism implies that the intramolecular dinuclear zinc catalyst is very important for future research into the copolymerization of other epoxides with CO2.