Enantioselective Ring Opening Of Epoxides Research Articles

Biocatalytic approaches for enantio and diastereoselective synthesis of chiral β-nitroalcohols.

Chiral β-nitroalcohols find significant application in organic synthesis due to the versatile reactivity of hydroxyl and nitro functionalities attached to one or two vicinal asymmetric centers. They are key building blocks of several important pharmaceuticals, bioactive molecules, and fine chemicals. With the growing demand to develop clean and green methods for their synthesis, biocatalytic methods have gained tremendous importance among the existing asymmetric synthesis routes. Over the years, different biocatalytic strategies for the asymmetric synthesis of β-nitroalcohol stereoisomers have been developed. They can be majorly classified as (a) kinetic resolution, (b) dynamic kinetic resolution, (c) Henry reaction, (d) retro-Henry reaction, (e) asymmetric reduction, and (f) enantioselective epoxide ring-opening. This review aims to provide an overview of the above biocatalytic strategies, and their comparison along with future prospects. Essentially, it presents an enzyme-toolbox for the asymmetric synthesis of β-nitroalcohol enantiomers and diastereomers.

Metal-Catalyzed Directed Regio- and Enantioselective Ring-Opening of Epoxides.

Control of regio- and stereoselectivity of chemical reactions is the central theme in synthetic chemistry. Regioselective and enantiospecific ring opening of readily available enantioenriched epoxides precursors provides a straightforward access to diverse highly functionalized molecules which can serve as chiral building blocks for synthesis of biologically active compounds. However, prior to our research work, the scope of catalytic highly regioselective ring opening of epoxides is limited to structurally or electronically biased epoxides, such as terminal and aromatic epoxides. Regioselective ring-opening of epoxides with substituents on both sides demonstrating similar steric and electronic effects is still a formidable challenge for organic chemists. To address this challenge, our approach is to use the readily available functional moiety incorporated in an epoxide as a directing group to realize the regioselective nucleophilic attack on the oxirane ring. Alternatively, asymmetric ring-opening of epoxides can also provide the ring-opening products in highly enantioenriched form. However, excellent results are usually obtained in the case of the kinetic resolution of terminal epoxides or the desymmetrization of meso-epoxides. In these cases, the issue of regiocontrol of the ring-opening is circumvented or minimized. Based on our successful results of regioselective ring-opening of functionalized epoxides by implementing the directed ring-opening strategy, we also investigated the enantioselective ring-opening of internal epoxides bearing a functional moiety as directing group. This Account summarizes our research on metal-catalyzed directed ring-opening reactions of epoxides, which encompasses the following breakthroughs: (1) highly regioselective ring-opening of various substrates including epoxy allylic alcohols, epoxy homoallylic alcohols and epoxy allylic sulfonamides with a variety of N-, O-, and halide-nucleophiles catalyzed by W-, Mo-, or Ni-salt; (2) first kinetic resolutions of epoxy allylic alcohols, epoxy homoallylic alcohols, and epoxy allylic sulfonamides with various amines as nucleophiles, which were catalyzed by W-bishydroxamic acid (W-BHA), nickel-BINAM, and Gd-N,N'-dioxide catalytic system, respectively; (3) successful implementation of the strategy of combined asymmetric syntheses by the combination of the enantioselective epoxidation and the enantioselective ring-opening of 2,3-epoxy alcohols establishing a new entry to prepare amino alcohols in regio-, diastereo-, and enantiomerically pure form.

Enantioselective ring opening of epoxides with TMSN3 by macrocyclic oligomer-supported Cr(III)–salen catalysts

Three Cr(III)–salen catalysts supported onto macrocyclic oligomeric cyclooctene through linkers of different lengths were synthesized. The influences of the linker length and the oligomeric support on the activity and the enantioselectivity of catalysts were investigated in the asymmetric ring opening of a meso-epoxide and the kinetic resolution of terminal epoxides. For both reactions all three catalysts exhibited significantly higher catalytic efficiency than the unsupported monomeric Cr(III)–salen catalyst. The catalyst with the shortest linker 1 showed the highest reaction rate while the catalyst with the longest linker 3 afforded the highest enantioselectivity in both reactions. The recoverability of catalyst 1 was also studied.

Mechanistic Investigations of Cooperative Catalysis in the Enantioselective Fluorination of Epoxides

This report describes mechanistic studies of the (salen)Co- and amine-cocatalyzed enantioselective ring opening of epoxides by fluoride. The kinetics of the reaction, as determined by in situ (19)F NMR analysis, are characterized by apparent first-order dependence on (salen)Co. Substituent effects, nonlinear effects, and reactivity with a linked (salen)Co catalyst provide evidence for a rate-limiting, bimetallic ring-opening step. To account for these divergent data, we propose a mechanism wherein the active nucleophilic fluorine species is a cobalt fluoride that forms a resting-state dimer. Axial ligation of the amine cocatalyst to (salen)Co facilitates dimer dissociation and is the origin of the observed cooperativity. On the basis of these studies, we show that significant improvements in the rates, turnover numbers, and substrate scope of the fluoride ring-opening reactions can be realized through the use of a linked salen framework. Application of this catalyst system to a rapid (5 min) fluorination to generate the unlabeled analog of a known PET tracer, F-MISO, is reported.

ChemInform Abstract: Catalytic Enantioselective Ring‐Opening Reaction of meso‐Epoxides with ArSeH Using a (Salen)Ti(IV) Complex.

AbstractOptimum reaction conditions are examined for the enantioselective ring opening of epoxides with arylselenols using a (salen)Ti(IV) complex.

Enantioselective epoxide ring opening catalyzed by bis(tetrahydroisoquinoline) N,N′-dioxides

Four bis(tetrahydroisoquinoline) N,N′-dioxides were used as catalysts for the epoxide ring opening with tetrachlorosilane under various conditions. A strong solvent effect on asymmetric induction was observed for each of the used catalysts. The highest achieved asymmetric induction for the opening of meso-stilbene oxide was 69% ee. Regarding the cycloalkene oxides, 56% ee was obtained in the reaction with cyclooctene oxide.

ChemInform Abstract: Enantioselective Ring Opening of Epoxides by Fluoride Anion Promoted by a Cooperative Dual‐Catalyst System.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes: An Efficient Method for the Synthesis of Optically Active 1,2-Diol Monoethers.

Useful chiral building blocks such as 1,2-diols can be obtained by the enantioselective ring opening of achiral epoxides with oxygen nucleophiles. The ring opening is carried out effectively (up to 94 % ee) with 4-methoxyphenol and catalytic amounts of gallium complexes. The novel complex GaSO 1 displays a particularly high catalytic activity.

Enantioselective Ring Opening of Epoxides by Fluoride Anion Promoted by a Cooperative Dual-Catalyst System

An enantioselective method for the synthesis of beta-fluoroalcohols by catalytic nucleophilic fluorination of epoxides is described. Mild reaction conditions and high selectivity are made possible by the use of benzoyl fluoride as a soluble, latent source of fluoride anion. A chiral amine and chiral Lewis acid serve as cooperative catalysts for desymmetrizations of five- through eight-membered cyclic epoxides, affording products in up to 95% ee. The cocatalytic protocol is also effective for kinetic resolutions of racemic terminal epoxides, which proceed with k(rel) values as high as 300.

Cover Picture: Catalytic Promiscuity of Halohydrin Dehalogenase and its Application in Enantioselective Epoxide Ring Opening (ChemBioChem 7/2008)

The cover picture shows a close-up of the promiscuous halide binding site of halohydrin dehalogenase, an enzyme that catalyzes enantioselective epoxide ring opening with a diversity of anionic nucleophiles. Also shown are conversions that give good yields of building blocks for a range of useful, highly enantioenriched, chiral compounds, including cyanoalcohols, nitroalcohols, and oxazolidinones. These have potential applications in agrochemicals, pharmaceuticals, and polymer chemistry. In the background, recombinant dehalogenase-producing E. coli colonies appear violet on an eosin–methylene blue indicator plate when exposed to a chloroalcohol substrate. For more information, see the communication by D. B. Janssen et al. on p. 1048 ff. of this issue.

Catalytic Promiscuity of Halohydrin Dehalogenase and its Application in Enantioselective Epoxide Ring Opening

Catalytic Promiscuity of Halohydrin Dehalogenase and its Application in Enantioselective Epoxide Ring Opening

Enantioselective Ring Opening of Epoxides with Silicon Tetrachloride in the Presence of a Chiral Lewis Base: Mechanism Studies

AbstractThe enantioselective ring opening of meso‐epoxides (from both cyclic and acyclic olefins) with silicon tetrachloride under catalysis by chiral phosphoramides affords enantiomerically enriched chlorohydrins in excellent yields. Experiments designed to elucidate the mechanistic foundation and origins of enantioselectivity are described. From studies on the loading and stoichiometry of the reagent (SiCl4) and the catalyst [(R)‐1] it was established that only one chloride per SiCl4 is delivered and that the nature of reactive species does not change over the course of the reaction. Kinetic studies together with asymmetric amplification experiments have suggested that more than one catalyst molecule may be bound to SiCl4 in the stereochemistry‐determining transition structure.

Efficient catalytic synthesis of optically pure 1,2-azido alcohols through enantioselective epoxide ring opening with HN 3

Chiral binuclear Co(salen) complexes bearing Lewis acid of group 13 metal chlorides show very high catalytic activity and enantioselectivity for the ring opening of epoxides using HN 3 as azide source. It provides a facile and practical synthetic route to a wide range of chiral nonracemic 1,2-azido alcohols and related compounds in one-pot synthesis with excellent selectivity (92.0–99.6% e.e.) under mild conditions. The presence of Lewis acid of group 13 shows a strong synergistic effect.

Enantioselective Ring Opening of Epoxides with Cyanide Catalyzed by Halohydrin Dehalogenases: A New Approach to Non‐Racemic β‐Hydroxy Nitriles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Regio‐ and Enantioselective Ring‐Opening of Epoxides with HMDST: A Straightforward Access to 1,2‐Mercaptoalcohols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enantioselective Ring Opening of Epoxides with Cyanide Catalysed by Halohydrin Dehalogenases: A New Approach to Non‐Racemic β‐Hydroxy Nitriles

AbstractHalohydrin dehalogenases (HheA, HheB and HheC) were found to efficiently catalyse a carbon‐carbon bond forming reaction between terminal aliphatic epoxides and cyanide, yielding β‐hydroxy nitriles. With all three enzymes nucleophilic ring opening of epoxides proceeds with high regioselectivity to the β‐carbon atom. Activity, enantioselectivity and enantiopreference depend on the type of enzyme and the substrate structure. HheC was found to be the most selective among the tested enzymes. The enantioselectivity toward monosubstituted epoxides varies from moderate to high (E=5–106), while resolution of 2,2‐disubstituted epoxides proceeds with very high enantioselectivity (E=141 and 200). The results show that halohydrin dehalogenases may become attractive catalysts for the facile preparation of enantiopure β‐hydroxy nitriles from racemic epoxides.

Regio- and Enantioselective Ring-Opening of Epoxides with HMDST: A Straightforward Access to 1,2-Mercaptoalcohols

TBAF-catalyzed reaction of a range of substituted epoxides with hexamethyldisilathiane smoothly affords a direct and simple access to β-mercaptoalcohols in a highly regio- and stereoselective way.

On the activity of chiral chromium salen complexes covalently bound to solid silicates for the enantioselective epoxide ring opening

Two series of solid catalysts in which a chiral chromium salen complex has been anchored on aminopropyl-functionalized SiO 2, ITQ-2 or MCM-41 have been prepared. In those catalysts in which anchoring of the complex was accomplished through coordination with the metal high enantiomeric excesses were obtained (up to 70% enantiomeric excess (e.e.)), but the complex leaches to the solution on a large extent. In contrast, for those other solids in which the complex is attached to the surface by covalent linkage to the ligand no leaching was observed, but the e.e. were modest (below 20%) compared to those obtained in homogeneous catalysis under comparable conditions (above 50%).

Enantioselective ring-opening of epoxides by HF-reagents: Asymmetric synthesis of fluoro lactones

The asymmetric ring opening of meso- and racemic-epoxides with different HF-reagents mediated by enantiopure (salen)chromium chloride provides optically active fluorohydrins with maximum 90% e.e. This reaction as well as lipase-catalyzed deracemization of a fluorohydrin is applied to synthesize a building block for the preparation of both enantiomers of a fluorinated analogue of the prostaglandin biosynthesis inhibitor lasiodiplodin using a cyclizing olefin metathesis reaction as a key-step.

Enantioselective introduction of fluoride into organic compounds: First asymmetric ring opening of epoxides by hydrofluorinating reagents

The first enantioselective epoxide ring opening with hydrofluorinating agents mediated by chiral non-racemic Lewis acids is reported. The reaction of cyclohexene oxide ( 1) with KHF 2/18-crown-6 is trans-diastereoselective and proceeds with 55% ee to form ( R,R)-(−)-2-fluorocyclohexanol ( 2) in the presence of Jacobsen’s ( S,S) -(+)-(salen)chromium chloride complex A. From racemic epoxides such as styrene oxide ( 9) or phenyl glycidether ( 13), mainly or exclusively the products with fluorine in primary position are formed with 90 or 62% ee, respectively. In all cases minor amounts of corresponding chlorohydrins are formed.