Enantioselective Epoxidation Research Articles

Using X-ray crystallography to validate the computational design of enantioselective epoxide hydrolases

Using X-ray crystallography to validate the computational design of enantioselective epoxide hydrolases

(Salen)Mn(III) Catalyzed Asymmetric Epoxidation Reactions by Hydrogen Peroxide in Water: A Green Protocol.

Enantioselective epoxidation reactions of some chosen reactive alkenes by a chiral Mn(III) salen catalyst were performed in H2O employing H2O2 as oxidant and diethyltetradecylamine N-oxide (AOE-14) as surfactant. This procedure represents an environmentally benign protocol which leads to e.e. values ranging from good to excellent (up to 95%).

ChemInform Abstract: Biomimetic Epoxidation in Aqueous Media Catalyzed by Cyclic Dipeptides.

AbstractThe enantioselective organocatalyzed epoxidation of α,β‐unsaturated ketones by 2,5‐diketopiperazines in aqueous media is reported.

ChemInform Abstract: Iron Catalyzed Highly Enantioselective Epoxidation of Cyclic Aliphatic Enones with Aqueous H2O2.

AbstractSeven iron complexes with a C1‐symmetric tetradentate N‐based ligand are synthesized and characterized.

Engineering P450 Peroxygenase to Catalyze Highly Enantioselective Epoxidation of cis-β-Methylstyrenes.

P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site-directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were studied. The T213M mutant is found to be the first engineered P450 peroxygenase that shows highly enantioselective epoxidation of cis-β-methylstyrenes, with up to 91 % ee. Molecular modeling studies provide insights into the different catalytic activity of the T213M mutant and the T213Y mutant in the epoxidation of cis-β-methylstyrene. The results of the calculations also contribute to a better understanding of the substrate specificity and configuration control for the regio- and stereoselective peroxygenation catalyzed by the T213M mutant.

ChemInform Abstract: Enantioselective Epoxidation of Olefins with H2O2 Catalyzed by Bioinspired Aminopyridine Manganese Complexes.

A novel family of bioinspired manganese(II) complexes bearing chiral aminopyridine ligands that possessed additional aromatic groups and strong donating dimethylamino groups were synthesized and characterized. These manganese complexes exhibited efficient and improved activities in the asymmetric epoxidation of various olefins, such as styrene derivatives (up to 93% ee) with H2O2 as the oxidant, even with a catalytic amount of carboxylic acid as the additive.

Ti-salalen mediated asymmetric epoxidation of olefins with H2O2: Effect of ligand on the catalytic performance, and insight into the oxidation mechanism

The highly enantioselective epoxidation of several conjugated olefins with H2O2 in the presence of five chiral titanium(IV) salalen (dihydrosalen) complexes has been studied, with focus on the effects of substituents (electronic and steric) on the epoxide yield and enantioselectivity. The introduction of electron acceptors at the ligand’s remote positions enhances the catalytic reactivity, without drastic effect on the stereoselectivity and ultimate catalytic efficiency. In turn, the replacement of Ph substituents of the ligand core with o-MeO-Ph and o-Et-Ph substituents leads to the enhancement in enantioselectivity (up to 99.8% ee), conversion (up to 100%) and efficiency (up to 125 TN). Kinetic and Hammett data provide evidence in favour of a stepwise epoxidation mechanism on Ti-salalen catalysts. As compared to Ti-salan protagonists, Ti-salalen catalysts exhibit much higher activity and efficiency, and in most cases comparable enantioselectivity. Kinetic peculiarities of epoxidations on Ti-salalen and Ti-salan complexes are considered.

Modified Ti/MCM-41 catalysts for enantioselective epoxidation of styrene

Ti sites grafted on MCM-41, pretreated at different temperatures, have been modified with chiral tartrates, leading to different species. Those solids are active catalyst for the epoxidation of styrene with tert-butyl hydroperoxide, although their efficiency is not optimal, mainly due to the subsequent epoxide rearrangement to phenyl acetaldehyde and further oxidation of it. Styrene oxide is obtained with moderate enantioselectivity, in the range of 55–62% e.e., and the best overall results correspond to the use of MCM-41 calcined at the lowest temperature (550°C). These results are much better with regard to styrene oxide selectivity than those obtained in homogeneous phase under the same conditions, whereas enantioselectivity is similar. The heterogeneous catalysts are recoverable, but only partially due to a loss in activity, although enantioselectivity is kept at similar levels, demonstrating the stability of the supported Ti-tartrate species.

Eric N. Jacobsen

Eric N. Jacobsen

New Concepts for Increasing the Efficiency in Directed Evolution of Stereoselective Enzymes.

Directed evolution of stereo- and regioselective enzymes constitutes a prolific source of catalysts for asymmetric transformations in organic chemistry. In this endeavor (iterative) saturation mutagenesis at sites lining the binding pocket of enzymes has emerged as the method of choice, but uncertainties regarding the question of how to group many residues into randomization sites and how to choose optimal upward pathways persist. Two new approaches promise to beat the numbers problem effectively. One utilizes a single amino acid as building block for the randomization of a 10-residue site, the other also employs only one but possibly different amino acid at each position of a 9-residue site. The small but smart libraries provide highly enantioselective epoxide hydrolase or lipase mutants, respectively.

Iron Catalyzed Highly Enantioselective Epoxidation of Cyclic Aliphatic Enones with Aqueous H2O2.

An iron complex with a C1-symmetric tetradentate N-based ligand catalyzes the asymmetric epoxidation of cyclic enones and cyclohexene ketones with aqueous hydrogen peroxide, providing the corresponding epoxides in good to excellent yields and enantioselectivities (up to 99% yield, and 95% ee), under mild conditions and in short reaction times. Evidence is provided that reactions involve an electrophilic oxidant, and this element is employed in performing site selective epoxidation of enones containing two alkene sites.

Enantioselective Epoxidation of Olefins with H2O2 Catalyzed by Bioinspired Aminopyridine Manganese Complexes.

A novel family of bioinspired manganese(II) complexes bearing chiral aminopyridine ligands that possessed additional aromatic groups and strong donating dimethylamino groups were synthesized and characterized. These manganese complexes exhibited efficient and improved activities in the asymmetric epoxidation of various olefins, such as styrene derivatives (up to 93% ee) with H2O2 as the oxidant, even with a catalytic amount of carboxylic acid as the additive.

Enantioselective Epoxidations of Olefins with Various Oxidants on Bioinspired Mn Complexes: Evidence for Different Mechanisms and Chiral Additive Amplification

It has been demonstrated that chiral manganese aminopyridine complexes [LMnII(OTf)2] are able to epoxidize olefins with excellent enantioselectivities (up to 99% ee, several examples) with various terminal oxidants (H2O2, alkyl hydroperoxides, peroxyacids, and iodosylarenes). The mechanisms of enantioselective olefin epoxidations on aminopyridine manganese(II) complexes [LMnII(OTf)2] with different oxidants are considered. The analysis of reaction products and epoxidation enantioselelctivity, Hammett correlations, and isotopic (18O) labeling studies bear evidence in favor of the formation of different oxidizing species in the presence of different terminal oxidants. The addition of cocatalytic additives (carboxylic acid or H2O) dramatically changes the catalytic behavior of catalyst systems Mn complex/hydrogen peroxide and Mn complex/alkyl hydroperoxide; in the presence of additives, the catalyst systems with H2O2 and alkyl hydroperoxides demonstrate very similar behaviors. Remarkably, in the presence of ...

New biphenyl iminium salt catalysts for highly enantioselective asymmetric epoxidation: role of additional substitution and dihedral angle.

New biaryl iminium salt catalysts for enantioselective alkene epoxidation containing additional substitution in the heterocyclic ring are reported. The effects upon conformation and enantioselectivity of this additional substitution, and the influence of dihedral angle in these systems, has been investigated using a synthetic approach supported by density functional theory. Enantioselectivities of up to 97% ee were observed.

ChemInform Abstract: Mononuclear Nonheme Iron(III)‐Iodosylarene and High‐Valent Iron‐Oxo Complexes in Olefin Epoxidation Reactions.

AbstractA non‐heme Fe(III)‐complex, generated from Fe(II)‐complex (ITT) and chiral iodosoarene (CIB) in the presence of HClO4, is successfully applied to the catalytic enantioselective epoxidation of di‐ and trisubstituted α,β‐unsaturated enones.

Enantioselective Total Synthesis of the Proposed Structure of Furan-Containing Polyketide.

Enantioselective total synthesis of the proposed structure of furan-containing polyketide was accomplished. The key features include a chemo- and enantioselective epoxidation of 1,4-cyclohexadiene by Shi asymmetric epoxidation, a regioselective epoxide ring opening, chemo- and diastereoselective dihydroxylation of the conjugated dienone derivative, and vinylation of the lactone accompanied by formation of the furan ring.

ChemInform Abstract: Asymmetric Epoxidation of Alkylidenemalononitriles: Key Step for One‐Pot Approach to Enantioenriched 3‐Substituted Piperazin‐2‐ones.

AbstractAn enantioselective epoxidation of alkylidenemalononitriles using a cinchona‐derived thiourea as the organocatalyst and cumyl hydroperoxide as the oxidant is reported.

Sharpless Asymmetrical Epoxidation: An Overview

Sharpless enantioselective epoxidation of achiral primary allyl alcohols is one of the best reaction discovered during the last about three decades. The reaction was typically named after discovery of this by Karl Barry Sharpless. For this discovery Sharpless received the Nobel Prize for medicinal chemistry in the year 2001. This reaction is stearoselective, i.e. it produces only enantionmers as final product. This reaction converts primary and secondary allylic alcohols into the 2, 3 epoxy alcohols. The final enantionmers which is formed will be a stereoselective depending upon the catalyst used during the same reaction. This reactions turns to be industry beneficial due to its applicability and high yield of products in the reaction.

Epoxide hydrolase-catalyzed enantioselective conversion of trans-stilbene oxide: Insights into the reaction mechanism from steady-state and pre-steady-state enzyme kinetics

A detailed kinetic study based on steady-state and pre-steady-state measurements is described for the highly enantioselective epoxide hydrolase Kau2. The enzyme, which is a member of the α/β-hydrolase fold family, preferentially reacts with the (S,S)-enantiomer of trans-stilbene oxide (TSO) with an E value of ∼200. The enzyme follows a classical two-step catalytic mechanism with formation of an alkyl-enzyme intermediate in the first step and hydrolysis of this intermediate in a rate-limiting second step. Tryptophan fluorescence quenching during TSO conversion appears to correlate with alkylation of the enzyme. The steady-state data are consistent with (S,S) and (R,R)-TSO being two competing substrates with marked differences in kcat and KM values. The high enantiopreference of the epoxide hydrolase is best explained by pronounced differences in the second-order alkylation rate constant (k2/KS) and the alkyl-enzyme hydrolysis rate k3 between the (S,S) and (R,R)-enantiomers of TSO. Our data suggest that during conversion of (S,S)-TSO the two active site tyrosines, Tyr157 and Tyr259, serve mainly as electrophilic catalysts in the alkylation half-reaction, polarizing the oxirane oxygen of the bound epoxide through hydrogen bond formation, however, without fully donating their hydrogens to the forming alkyl-enzyme intermediate.

Novel chiral thiourea organocatalysts for the catalytic asymmetric oxaziridination

Catalytic enantioselective oxaziridination is one of the challenging reactions in the oxidation of organic molecules. In this article, a series of novel chiral thiourea moleculars were synthesized from natural cinchona alkaloids and primary amines. By using these molecules as organocatalysts and m-chloroperoxybenzoicacid (m-CPBA) as the oxidant, a methodology on highly enantioselective epoxidation of aldimines has been developed. Several optically active oxaziridines have been constructed in good yields (up to 95%) and moderate to excellent enantioselectivities (up to 99% ee). A plausible transition state was also proposed.