Catalytic Asymmetric Epoxidation Research Articles

A Lewis Acid-Controlled Enantiodivergent Epoxidation of Aldehydes.

Two epoxidation catalysts, one of which consists of two VANOL ligands and an aluminum and the other that consists of two VANOL ligands and a boron, were compared. Both catalysts are highly effective in the catalytic asymmetric epoxidation of a variety of aromatic and aliphatic aldehydes with diazoacetamides, giving high yields and excellent asymmetric inductions. The aluminum catalyst is effective at 0 °C and the boron catalyst at -40 °C. Although both the aluminum and boron catalysts of (R)-VANOL give very high asymmetric inductions (up to 99% ee), they give opposite enantiomers of the epoxide. The mechanism, rate- and enantioselectivity-determining step, and origin of enantiodivergence are evaluated using density functional theory calculations.

Remote Amino Acid Recognition Enables Effective Hydrogen Peroxide Activation at a Manganese Oxidation Catalyst.

Precise delivery of a proton plays a key role in O2 activation at iron oxygenases, enabling the crucial O−O cleavage step that generates the oxidizing high‐valent metal–oxo species. Such a proton is delivered by acidic residues that may either directly bind the iron center or lie in its second coordination sphere. Herein, a supramolecular strategy for enzyme‐like H2O2 activation at a biologically inspired manganese catalyst, with a nearly stoichiometric amount (1–1.5 equiv) of a carboxylic acid is disclosed. Key for this strategy is the incorporation of an α,ω‐amino acid in the second coordination sphere of a chiral catalyst via remote ammonium‐crown ether recognition. The properly positioned carboxylic acid function enables effective activation of hydrogen peroxide, leading to catalytic asymmetric epoxidation. Modulation of both amino acid and catalyst structure can tune the efficiency and the enantioselectivity of the reaction, and a study on the oxidative degradation pathway of the system is presented.

Remote Amino Acid Recognition Enables Effective Hydrogen Peroxide Activation at a Manganese Oxidation Catalyst

AbstractPrecise delivery of a proton plays a key role in O2 activation at iron oxygenases, enabling the crucial O−O cleavage step that generates the oxidizing high‐valent metal–oxo species. Such a proton is delivered by acidic residues that may either directly bind the iron center or lie in its second coordination sphere. Herein, a supramolecular strategy for enzyme‐like H2O2 activation at a biologically inspired manganese catalyst, with a nearly stoichiometric amount (1–1.5 equiv) of a carboxylic acid is disclosed. Key for this strategy is the incorporation of an α,ω‐amino acid in the second coordination sphere of a chiral catalyst via remote ammonium‐crown ether recognition. The properly positioned carboxylic acid function enables effective activation of hydrogen peroxide, leading to catalytic asymmetric epoxidation. Modulation of both amino acid and catalyst structure can tune the efficiency and the enantioselectivity of the reaction, and a study on the oxidative degradation pathway of the system is presented.

Catalytic Asymmetric Darzens-Type Epoxidation of Diazoesters: Highly Enantioselective Synthesis of Trisubstituted Epoxides.

Highly enantioselective Darzens-type epoxidation of diazoesters with glyoxal derivatives was accomplished using a chiral boron-Lewis acid catalyst, which facilitated asymmetric synthesis of trisubstituted α,β-epoxy esters. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in high yield (up to 99 %) with excellent enantio- and diastereoselectivity (up to >99 % ee and >20:1 dr, respectively). The synthetic potential of this method was illustrated by conversion of the products to various compounds such as epoxy γ-butyrolactone, tertiary β-hydroxy ketone and epoxy diester.

Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents

An enantioselective epoxidation of α-substituted vinyl ketones was realized to construct the key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields with good enantioselectivities by employing a chiral N,N'-dioxide/ScIII complex as the chiral catalyst and 35% aq. H2O2 as the oxidant. It enabled the facile transformation for optically active isavuconazole, efinaconazole, and other potential antifungal agents.

Corrigendum to “Immobilization of (tartrate-salen)Mn(III) polymer complexes into SBA-15 for catalytic asymmetric epoxidation of alkenes” [Mol. Catal. 495 (2020) 111146

Corrigendum to “Immobilization of (tartrate-salen)Mn(III) polymer complexes into SBA-15 for catalytic asymmetric epoxidation of alkenes” [Mol. Catal. 495 (2020) 111146

Epoxide Syntheses and Ring-Opening Reactions in Drug Development

This review concentrates on success stories from the synthesis of approved medicines and drug candidates using epoxide chemistry in the development of robust and efficient syntheses at large scale. The focus is on those parts of each synthesis related to the substrate-controlled/diastereoselective and catalytic asymmetric synthesis of epoxide intermediates and their subsequent ring-opening reactions with various nucleophiles. These are described in the form of case studies of high profile pharmaceuticals spanning a diverse range of indications and molecular scaffolds such as heterocycles, terpenes, steroids, peptidomimetics, alkaloids and main stream small molecules. Representative examples include, but are not limited to the antihypertensive diltiazem, the antidepressant reboxetine, the HIV protease inhibitors atazanavir and indinavir, efinaconazole and related triazole antifungals, tasimelteon for sleep disorders, the anticancer agent carfilzomib, the anticoagulant rivaroxaban the antibiotic linezolid and the antiviral oseltamivir. Emphasis is given on aspects of catalytic asymmetric epoxidation employing metals with chiral ligands particularly with the Sharpless and Jacobsen–Katsuki methods as well as organocatalysts such as the chiral ketones of Shi and Yang, Pages’s chiral iminium salts and typical chiral phase transfer agents.

Immobilization of (tartrate-salen)Mn(III) polymer complexes into SBA-15 for catalytic asymmetric epoxidation of alkenes

A series of (tartrate-salen)Mn(III) polymer complexes were prepared and immobilized into SBA-15, being subsequently employed as catalysts in the asymmetric epoxidation of alkenes. 1H NMR, FT-IR, UV–vis, elemental analysis, GPC and ICP-AES demonstrated the successful synthesis of polymer complexes, while powdered XRD, nitrogen physisorption and XPS studies proved the immobilization of polymer complexes into SBA-15. Both homogeneous and heterogeneous catalysis revealed that configurations of major epoxide products were still determined by salen chirality but e.e. values could be improved when tartrate and salen were configurationally identical. Combinations of (R,R)-salen with (R,R)-tartrate usually offered higher enantioselectivities. SBA-15 was satisfactory supporting material due to the high enantioselectivities and recycling yields obtained. The synthesized SBA-15-supported (tartrate-salen)Mn(III) catalysts showed continuous high enantioselectivities for epoxidation of α-methylstyrene, indicating great prospects for large-scale production.

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL‐Derived Chiral Borate Catalysts

AbstractA highly diastereo‐ and enantioselective method for the epoxidation of aldehydes with α‐diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL. Catalysts generated from BINOL and VAPOL are ineffective catalysts. An application is shown for access to the side‐chain of taxol.

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL-Derived Chiral Borate Catalysts.

A highly diastereo- and enantioselective method for the epoxidation of aldehydes with α-diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL. Catalysts generated from BINOL and VAPOL are ineffective catalysts. An application is shown for access to the side-chain of taxol.

Chiral porphyrin imine manganese complex as catalyst for asymmetric epoxidation of styrene derivatives.

New chiral porphyrin imine was synthesized from (S)-3-benzyl-2-methyl-4-phenylbutanal according to dipyrromethane method using trifluoroacetic acid, BF3 etherate, and p-chloranil. Manganese complex of this chiral porphyrin imine ligand was used as catalyst in the asymmetric epoxidation of styrene derivatives possessing different substituents. Styrene derivatives possessing electron withdrawing groups gave the corresponding chiral epoxides in high yield up to 98% and ee up to 99%. The mechanism for the catalytic asymmetric epoxidation was also discussed based on transfer of oxygen.

Catalytic Asymmetric Epoxidation of Electron‐Deficient Enynes Promoted by Chiral N,N′‐Dioxide‐Scandium(III) Complex

AbstractAn asymmetric epoxidation of electron‐deficient enynes with environmentally benign aqueous hydrogen peroxide as oxidant has been accomplished by developing a chiral N,N′‐dioxide‐Scandium(III) complex catalytic system. In the presence of 0.5–2 mol% catalyst, a variety of trisubstituted alkynyl oxiranes were obtained in high yields (up to 97%) with excellent ee values (up to 99%). Furthermore, control experiments provide a fundamental insight into the reaction mechanism.magnified image

Chiral Mesoporous Silicates Immobilizing Titanium Dioxide for Catalytic Asymmetric Epoxidation of Alkenes

Two kinds of titanium-containing silicates were prepared by doping of titanium salt and chiral additive in a sol-gel process, which were further modified by chiral sulfonyl chloride in order for catalytic asymmetric epoxidation of alkenes. These titanium-containing materials had good porosities, ordered pore size distributions, high titanium incorporation yields, ordered morphologies, as well as internal chiral configurations. Particularly, they contained a lot of titanium dioxide particles according to TEM. In catalysis, the titanium silicates showed good conversion of alkenes, satisfactory yields and e.e. values of epoxides. The chiral inducing synergy appeared between silicate matrix and attached ligand, which was significant for transformations of styrene and α-methylstyrene. Moreover, iodosylbenzene, tert-butyl hydroperoxide and hydrogen peroxide were all promising oxidants. In addition, the present titanium catalysts showed satisfactory recycling behaviors and chemical stabilities. This work would contribute to the design of efficient chiral catalysts.

Epimeric Face-Selective Oxidations and Diastereodivergent Transannular Oxonium Ion Formation Fragmentations: Computational Modeling and Total Syntheses of 12-Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene C, and Marilzabicycloallene D.

The total syntheses of 12-epoxyobtusallene IV, 12-epoxyobtusallene II, obtusallene X, marilzabicycloallene C, and marilzabicycloallene D as halogenated C15-acetogenin 12-membered bicyclic and tricyclic ether bromoallene-containing marine metabolites from Laurencia species are described. Two enantiomerically pure C4-epimeric dioxabicyclo[8.2.1]tridecenes were synthesized by E-selective ring-closing metathesis where their absolute stereochemistry was previously set via catalytic asymmetric homoallylic epoxidation and elaborated via regioselective epoxide-ring opening and diastereoselective bromoetherification. Epimeric face-selective oxidation of their Δ12,13 olefins followed by bromoallene installation allowed access to the oppositely configured 12,13-epoxides of 12-epoxyobtusallene II and 12-epoxyobtusallene IV. Subsequent exploration of their putative biomimetic oxonium ion formation-fragmentations reactions revealed diastereodivergent pathways giving marilzabicycloallene C and obtusallene X, respectively. The original configurations of the substrates evidently control oxonium ion formation and their subsequent preferred mode of fragmentation by nucleophilic attack at C9 or C12. Quantum modeling of this stereoselectivity at the ωB97X-D/Def2-TZVPPD/SCRF = methanol level revealed that in addition to direction resulting from hydrogen bonding, the dipole moment of the ion-pair transition state is an important factor. Marilzabicycloallene D as a pentahalogenated 12-membered bicyclic ether bromoallene was synthesized by a face-selective chloronium ion initiated oxonium ion formation-fragmentation process followed by subsequent bromoallene installation.

ChemInform Abstract: Novel Chiral Schiff Base/Ti(IV) Catalysts for the Catalytic Asymmetric Epoxidation of N‐Alkenyl Sulfonamides.

A new method has been developed for the catalytic asymmetric epoxidation of N-alkenyl sulfonamides in the presence of a Schiff base derived from hydroquinine and Ti(Oi-Pr)4. This reaction proceeds under mild conditions, providing facile access to chiral epoxy sulfonamides in good yields (up to 95%) with excellent enantioselectivities (up to 97% ee).

Quest for Efficient Catalysts based on Zinc tert‐Butyl Peroxides for Asymmetric Epoxidation of Enones: C2‐ vs C1‐Symmetric Auxiliaries

AbstractZinc tert‐butyl peroxide‐based catalysts for the asymmetric epoxidation of enones using tert‐butyl hydroperoxide as an oxidant have been developed. A comparative study of chiral monoanioninc N,N′‐bidentate ligands, C2‐symmetric bisoxazolinates and C1‐symmetric enaminooxazolinates, revealed excellent performance of C1‐symmetric auxiliary ligands on catalytic asymmetric epoxidation of enones (up to 96% yield, 91% ee).magnified image

Novel chiral Schiff base/Ti(iv) catalysts for the catalytic asymmetric epoxidation of N-alkenyl sulfonamides

A new method has been developed for the catalytic asymmetric epoxidation of N-alkenyl sulfonamides in the presence of a Schiff base derived from hydroquinine and Ti(Oi-Pr)4. This reaction proceeds under mild conditions, providing facile access to chiral epoxy sulfonamides in good yields (up to 95%) with excellent enantioselectivities (up to 97% ee).

Creation of chiral materials: Yesterday, today and tomorrow

Chirality is a fundamental characteristic of nature and pervades the world. The chiral materials closely related to our life, especially our health. The thalidomide tragedy, lessons for drug safety and regulation from the late 1950s and the early 1960s, indicated the importance of creating chiral materials in optically pure form. Pasteur was the first to conduct chiral resolution for the preparation of optically active molecules before 1860. Since then, scientists including chemists started to search methods for creating chiral materials like enzyme. After more than one hundred years of efforts, chemists find that the synthetic chiral catalysts (also known as artificial enzymes) catalyzed asymmetric reactions is the door to creating chiral materials. From 1970 to 2001, many efficient and selective catalytic asymmetric reactions and methods have been developed for creating chiral materials. In particular, the successes of catalytic asymmetric hydrogenations and catalytic asymmetric epoxidations and their applications in industrial preparation of chiral drugs enable this research field to won the Nobel Prize for chemistry in 2001. To date, tremendous amount of chiral materials such as chiral pharmaceuticals, chiral agrochemicals, chiral liquid crystals were created in a high selective and efficient manner. We now can create chiral materials like enzymes by using asymmetric catalysis with artificial enzymes as catalysts. The Chinese chemists also made great contributions for creating chiral materials, especially in the past two decades. They developed a series of highly efficient chiral ligands and catalysts including the magical chiral spiro ligands and catalysts, the privileged chiral N , N ￠-dioxides, as well as many original organocatalysts. These catalysts are highly efficient for a wide range of reactions involving asymmetric hydrogenation, asymmetric carbon-carbon bond formations, and asymmetric carbon-heteroatom bond formations, providing chiral alcohols, chiral amines, chiral acids, etc. Many new asymmetric catalytic reactions, new concepts, new strategies were also developed by Chinese chemists, which afforded new methodologies for creating chiral materials. From this century, in order to meet the new demand of mankind on the chiral materials, scientists begin to develop green and sustainable methods for the accurate, powerful and environment-friendly creation of chiral materials. In addition, the creation of chiral materials has been in depth combined with life sciences, environmental sciences, materials science and information sciences, etc. This review focus on the main line of the discovery and development of asymmetric catalysis, in combination with the development in China, to give a brief overview for the journey of creation of chiral materials.

Total synthesis of pro-resolving and tissue-regenerative Protectin sulfido-conjugates

The stereospecific total synthesis of the pro-resolving and tissue-regenerative Protectin sulfido-conjugates: 16R,17S-PCTR1, 16R,17S-PCTR2, and 16R,17S-PCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 16S,17S-epoxy-Protectin methyl ester was synthesized using the Sharpless catalytic asymmetric epoxidation to generate the chiral centers at C16 and C17. A Cs2CO3 promoted coupling provided the skipped diyne intermediate. Wittig reactions and epoxide opening with glutathione, l-cysteinylglycine, and l-cysteine methyl ester hydrochloride, respectively, were the key steps in the synthesis.

立体および位置選択的な触媒的エポキシ化—配向基からどれだけの距離にあるオレフィンを選択的にエポキシ化できるか—

立体および位置選択的な触媒的エポキシ化—配向基からどれだけの距離にあるオレフィンを選択的にエポキシ化できるか—