Asymmetric Epoxidation Reaction Research Articles

Layered zinc and lanthanum hydroxide nitrates hosting chiral sulphonato-(salen)manganese(III) complex catalyzed asymmetric epoxidation reactions

Layered zinc and lanthanum hydroxide nitrates were first applied as two ion-exchangeable supports for immobilizing a chiral sulphonato-(salen)manganese(III) complex, and the resulted catalysts were characterized by FT-IR, elemental analysis, ICP-AES, TGA, conductivity, XRD, nitrogen physisorption, along with aqueous particle size and zeta potential. Heterogeneous catalysts showed moderate to good conversions and excellent enantioselectivities in epoxidation of styrene and α-methylstyrene when iodosylbenzene was employed as terminal oxidant. Furthermore, the superiority came from heterogeneity, and only filtration could lead to an effective separation of catalyst from product solution.

ChemInform Abstract: Organocatalytic Asymmetric Epoxidation and Tandem Epoxidation/Passerini Reaction under Eco‐Friendly Reaction Conditions.

AbstractDiarylprolinol silyl ethers are used as organocatalysts in asymmetric epoxidation reactions of α,β‐unsaturated aldehydes affording optically active epoxides (II) in high yields.

Molecularly enlarged S,S-BnTsDPEN ligands for iron-catalyzed asymmetric olefin epoxidation reactions using hydrogen peroxide

A convenient approach for the anchoring of S,S-BnTsDPEN ligands (S,S-N-tosyl-1,2-diphenylethylenediamine) to branched carbosilane scaffolds was investigated. It is based on a high-yielding reductive amination reaction between commercially available S,S-TsDPEN and readily accessible carbosilanes furnished with benzaldehyde terminal fragments. These molecularly enlarged ligands, bearing four S,S-BnTsDPEN units, and their simplified monomeric and “dimeric” analogues were evaluated in iron(III)-catalyzed asymmetric trans-stilbene epoxidation reactions using hydrogen peroxide as an environmentally benign oxidant. The catalytic investigations showed a large degree of variation in the activity and stereoselectivity of the series of DPEN catalysts. In combination with ESI-MS investigations, these data revealed an important role of the ligand orientation in determining the overall activity of the catalyst system. Accordingly, a suitable design of the molecularly enlarged ligands resulted in fully retained activity and selectivity in catalysis. Finally, a number of strategies for the recovery and reuse of the best performing carbosilane-tethered DPEN ligands were explored.

Hydroxamic Acids in Asymmetric Synthesis

Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst's center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed. Because of their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless asymmetric epoxidation, which uses the titanium-tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydroxamic acid as catalysts since then. This Account summarizes our research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as chiral ligands. We designed and synthesized a series of new hydroxamic acids, most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed epoxidation of allylic and homoallylic alcohols achieved higher activity and stereoselectivity than Sharpless asymmetric epoxidation in many cases. Changing the metal species led to a series of unprecedented asymmetric epoxidation reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely functionalized chiral epoxides with good yields and enantioselectivities.

Electronic helix theory-guided rational design of kinetic resolutions by means of the Sharpless asymmetric dihydroxylation reactions

Kinetic resolution represents a key chemical reaction strategy for asymmetric synthesis of optically enriched compounds, and it originates from a simple phenomenon that a pair of mirror images (enantiomers) of a racemate can react with different rates under a chiral environment. While highly efficient catalytic kinetic resolutions by means of the classical Sharpless asymmetric epoxidation (AE) reactions are well established in modern organic synthesis, such systems based on the arguably more versatile Sharpless asymmetric dihydroxylation (AD) processes, although long pursued and widely attempted, remain largely underexplored. With insights gained from a new electronic helix theory we recently developed for molecular chirality and chiral interactions, we were able to advance a proposal suggesting why this problem is challenging and how it might be solved. Guided by a new design concept aimed at identifying complimentary catalyst–substrate electronic interactions, we reported herein that not only can such elusive systems be generally feasible, but efficiencies well reach the highest levels known to date with chemical or enzymatic kinetic resolutions of any type.

Simple and Efficient Synthesis of (S)-Dapoxetine

A refinement in the synthetic strategy for (S)-dapoxetine 1 is described. The key features of synthetic strategy include (a) a Sharpless asymmetric epoxidation reaction and regioselective reductive ring opening of a 2,3-epoxy alcohol to elaborate the hydroxy-bearing stereogenic center at benzylic position; (b) regioselective functionalization of 1-naphthol and amine functionality through Mitsunobu procedures; and (c) Eschweiler–Clarke reductive methylation condition to access the target molecule.

Asymmetric Epoxidation of Chromenes Using Manganese(III) Complexes with Novel Chiral Salen-like Schiff Base Ligands

Three novel chiral salen-like schiff base ligands and their Mn(III) complexes containing different amino acid unit have been synthesized and characterized. Asymmetric epoxidation reactions show these complexes are effective catalysts for the chromenes with buffer NaOCl as terminal oxidant and pyridine N-oxide as co-catalyst in the presence of ionic liquid. Good-to -excellent enantioselectivity and acceptable yields can be obtained under optimum reaction conditions. Catalyst 4c gives the highest ee (95%) for 6-chloro-2,2-dimethylchromene among these catalytic performances. Furthermore, compared the enantioselectivity of catalyst 4c with the other two catalysts 4a and 4b, the positive experimental results suggest that the steric effect of the ligands plays an important role in the asymmetric catalysis. Asymmetric epoxidation of chromenes with Mn (III) complex containing amino acid moiety

Toward a computational tool predicting the stereochemical outcome of asymmetric reactions: Development of the molecular mechanics‐based program ACE and application to asymmetric epoxidation reactions

The development and application of ACE, a program that predicts the stereochemical outcome of asymmetric reactions is presented. As major implementations, ACE includes a genetic algorithm to carry out an efficient global conformational search combined with a conjugate gradient minimization routine for local optimization and a corner flap algorithm to search ring conformations. Further improvements have been made that enable ACE to generate Boltzmann populations of conformations, to investigate highly asynchronous reactions, to compute fluctuating partial atomic charges and solvation energy and to automatically construct reactants and products from libraries of catalysts and substrates. Validation on previously investigated reactions (asymmetric Diels Alder cycloadditions and organocatalyzed aldol reactions) followed by application to a number of alkene epoxidation reactions and a comparative study of DFT-derived and ACE-derived predictions demonstrate the accuracy and usefulness of ACE in the context of asymmetric catalyst design.

Novel nanohybrid materials based on l-leucine on hydrotalcite clays: Asymmetric epoxidation reaction of chalcona

The assembly of biorgano-guest to laminar inorganic solids is of increasing interest to their versatile applications in biotechnology or catalysis. We synthesized two different biohybrid materials based on l-leu into the hydrotalcite rehydrated under ultrasound treatment (HTrus), in which l-leu was immobilized by intercalation or by replacing of hydroxyl ions at the edge sites of HTrus. Separately l-leu and HTrus as catalysts showed very poor activity and lack of enantioselectivity in the epoxidation reaction of α,β-unsaturated ketones such as chalcone. Nevertheless, the catalysts presented high activity and even enantioselectivity towards the trans-(R,S)-epoxide depending on the l-leu location on the nanohybrid catalyst.

The first total synthesis of (−)-bitungolide E

The first total synthesis of (−)-bitungolide E is described. The key steps include a Myers’ alkylation, modified Evans’ syn aldol-reaction, using Crimmins protocol, Sharpless asymmetric epoxidation and ring-closing metathesis reaction.

Chiral Primary Amine Catalyzed Asymmetric Epoxidation of α‐Substituted Acroleins

Abstract1,1‐Disubstituted terminal alkenes remain challenging substrates in asymmetric epoxidation reactions. In this study, chiral primary amines are shown to catalyze the asymmetric epoxidation of α‐substituted acroleins, a versatile type of 1,1‐disubstituted terminal alkene. Among various chiral primary amines explored, the chiral primary‐tertiary vicinal diamine derived from trans‐1,2‐diphenylethane‐1,2‐diamine is identified as the optimal catalyst, which, in combination with 5‐sulfosalicyclic acid (5‐SSA), exhibits good catalytic activity (up to 95 % yield) and enantioselectivity (up to 88 % ee). Aqueous 2 M sodium chloride was found to be the optimal reaction media.

First total synthesis of achaetolide

The first total synthesis of achaetolide, a 10-membered macrolactone was achieved using Mitsunobu reaction and Grubbs ring-closing metathesis reaction as the key steps for ring construction. The desired stereo centres were generated by Jacobsen hydrolytic kinetic resolution, dihydroxylation and Sharpless asymmetric epoxidation reactions.

ChemInform Abstract: Homologation of Allylic Alcohols. An Approach to Cyclic and Acyclic Polyoxygenated Compounds.

Abstract The combination of the Sharpless asymmetric epoxidation reaction with a sulfur ylide mediated synthesis of allylic alcohols from epoxides provides a powerful iterative process for the production of polyoxygenated compounds. The alkene installed in the sulfur ylide reaction has also been used in a number of ring closing metathesis reactions to produce highly oxygenated cyclic compounds.

ChemInform Abstract: The Julia-Colonna Type Asymmetric Epoxidation Reaction Catalyzed by Soluble Oligo-L-leucines Containing an α-Aminoisobutyric Acid Residue: Importance of Helical Structure of the Catalyst on Asymmetric Induction.

Length-defined organic solvent soluble oligo-L-leucines containing an Aib residue were prepared by stepwise elongation and fragment condensation methods, and were used as catalysts in the Julia–Colonna asymmetric epoxidation reaction. The yield and enantioselectivity rose by increasing the number of amino acid units in the catalyst. The enantioselectivity was very sensitive to the reaction solvent. The IR characteristic bands (the amide I region) in CH2Cl2 indicated the soluble catalysts to be of helical structure in solution.

Zirconium(IV)- and hafnium(IV)-catalyzed highly enantioselective epoxidation of homoallylic and bishomoallylic alcohols.

In this report, zirconium(IV)- and hafnium(IV)-bishydroxamic acid complexes were utilized in the highly enantioselective epoxidation of homoallylic alcohols and bishomoallylic alcohols, which used to be quite difficult substrates for other types of asymmetric epoxidation reactions. The performance of the catalyst was improved by adding polar additive and molecular sieves. For homoallylic alcohols, the reaction could provide epoxy alcohols in up to 83% yield and up to 98% ee, while, for bishomoallylic alcohols, up to 79% yield and 99% ee of epoxy alcohols rather than cyclized tetrahydrofuran compounds could be obtained in most cases.

Modification of chiral dimethyl tartrate through transesterification: Immobilization on POSS and enantioselectivity reversal in sharpless asymmetric epoxidation

Modification of dimethyl tartrate has been investigated through transesterification with aminoalcohols to provide reactive functionalities for the covalent bonding of chiral tartrate to polyhedral oligomeric silsesquioxanes. The transesterification of dimethyl tartrate has been widely studied using different catalytic systems and reaction conditions. Through the proper selection of both the catalytic system and the reaction conditions, it is possible to achieve monosubstituted or bis-substituted tartrate derivatives as sole products. All the intermediate chiral tartrate-derived ligands were successfully used in the homogeneous enantioselective epoxidation of allylic alcohols providing moderate enantiomeric excess over the products. Attached amine groups have been used to support the modified tartrate ligands on to a haloaryl-functionalized silsesquioxane moiety. This final chiral tartrate ligand displays reverse enantioselectivity in the asymmetric epoxidation of allylic alcohols with regard to the starting dimethyl tartrate ligand, both molecules having the same chiral sign. However, the POSS-containing ligand can be easily recovered in almost quantitative yield and reused in asymmetric epoxidation reactions. In addition, recovered silsesquioxane-pendant ligand, though displaying decreasing catalytic activity in recycling epoxidation tests, showed very stable enantioselective behavior.

Asymmetric Catalysis in Confined Space Provided by l-Proline Functionalized Mesoporous Silica with Plugs in the Pore

Mesoporous silica having l-proline functionality and plugged pore structure was synthesized by direct microwave synthesis under acidic condition using Pluronic P123 as template and sodium metasilicate nonahydrate as silica source. The direct synthesis resulted in the prismatic or disk types with short channels and plugs in the pore structure. Due to the presence of plugs, dual mesoporosities with 7 and 3 nm pore diameter were generated leading to an existence of cavitation. Tri-functionality of this materials i.e. chiral organofunctional group, plugs, and short channel, would be useful for the asymmetric diethyl malonate addition reaction and asymmetric epoxidation reaction of α,β-unsaturated aldehydes. We proved that the formation of plugs in the mesoporous silica governs the formation of dual mesoporosities providing an enhancement of enantiomeric excess in the asymmetric catalysis. This finding might open an important application of the amino-acid organo multifunctionalized mesoporous silica for asymmetric reactions.

First stereoselective synthesis of synargentolide A and revision of absolute stereochemistry

The first stereoselective total synthesis of synargentolide A isolated from Syncolostemon argenteus has been achieved from commercially available ( R)-benzyl glycidyl ether using Sharpless asymmetric epoxidation and cross-metathesis reactions as the key steps. Comparing the spectral data of the synthesized and naturally occurring synargentolide A, the C4′ and C6′- stereogenic centers of the natural synargentolide A were assigned a corrected anti relationship.

Lanthanum(III)-Catalyzed Cyclopropanation

A lanthanum(III) triflate catalyzed cyclopropanation protocol involving the methylene transfer from epoxides to olefins is described. The resulting aldehydes and ketones are obtained in good yield and the reactions proceed with high ­diastereoselectivity. Furthermore, enantioenriched cyclopropanes can be obtained following asymmetric epoxidation and methylene transfer reactions.

ChemInform Abstract: Asymmetric Epoxidation, Michael Addition, and Triple Cascade Reaction Using Polymer‐Supported Prolinol‐Based Auxiliaries.

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