Regioselective Ring Opening Of Epoxides Research Articles

Regioselective Ring Opening of Epoxide with Alcohols: A Selective Route to α‐Alkylated Ketones and β‐Alkylated Secondary Alcohols

AbstractHerein, we demonstrated an effective protocol for the regioselective ring opening of epoxides with alcohols. By following this strategy, both α‐alkylated ketones and β‐alkylated secondary alcohols were selectively obtained by changing the reaction parameters. Compared to the previously reported protocols, this methodology was operated using considerably lower base at lower temperature. Notably, a wide array of substrates with tolerance of different functional groups was demonstrated. A series of control experiments and deuterium‐labelling experiments were performed to understand this catalytic process.

Environment Benign Bismuth Based Catalysts for the Expedite Regioselective Ring Opening of Epoxides Under Solvent Free Microwave Condition

AbstractBismuth‐based catalysts, namely Bi(PO4), (BiO)2CO3, BiF3, and Bi2(C2O4)3, are used as mild and efficient tools for the aminolysis of epoxides under solvent‐free conditions with microwave irradiation, which significantly reduced the reaction time. The catalysts employed are environment friendly, cost‐effective, and demonstrated high efficiency in terms of both high yields and regioselectivity.

Synthesis and examination of alkoxycyanobiphenyl mesogens with a single fluorine atom at specific locations in the tail

ABSTRACT Selective fluorination is a well-established technique to tailor and improve many of the physical properties of liquid crystals. Cyanobiphenyls are among the best-known and understood thermotropic liquid crystals and have served admirably as a testbed for structural modifications that can eventually be extended to other classes of liquid crystals. As such, and expanding on our earlier work, in the present study of the alkoxycyanobiphenyl M series, the individual tail sites of both 4’-(butoxy)[1,1’-biphenyl]-4-carbonitrile (M12) and 4’-(pentyloxy)[1,1’-biphenyl]-4-carbonitrile (M15) were selectively monofluorinated in order to examine the influence on the phase behavior. These fluorinated compounds were synthesized using epoxidation, regioselective epoxide opening and deoxyfluorination chemistry. In all the fluorinated compounds in both series a monotropic nematic phase was found in the cooling cycle. It was observed that as the fluorine atom on the tail moves closer to the core, the compounds exhibited a metastable room temperature nematic mesophase, but recrystallization invariably occurred. Both enantiomers of 4’-(2-fluorobutoxy)[1,1’-biphenyl]-4-carbonitrile were synthesized in high enantiomeric purity by regioselective opening of chiral epoxide intermediates followed by deoxyfluorination, as established by chiral high-performance liquid chromatography, and their phase behaviors were determined. Moreover, the average dipole moments of the synthesized fluorine substituted derivatives were also calculated.

Regioselective Ring-Opening of Terminal Epoxides Catalyzed by a Porous Metal Silicate Material.

Reductive ring-opening of epoxides is a green pathway for synthesizing highly value-added alcohols. In this study, we present a practically applicable approach for the synthesis of anti-Markovnikov-type alcohols with high yields from aliphatic and aromatic epoxides under mild conditions by developing porous metal silicate (PMS) catalysts. A PMS material PMS-20 consists of cobalt and nickel bimetal redox-active sites, exhibiting exceptional catalytic activity and selectivity in the reductive ring-opening of terminal epoxides with >99% yield of primary alcohols. Comparing with the existing methods using noble metals, PMS-20 exhibits broad substrate scope and excellent functional group tolerance by synergistic work between cobalt and nickel species, which is clarified by dual chamber cell system characterization and theoretical calculation results.

Construction of β-Acetoxy or β-Hydroxyl Disulfides via Highly Regioselective Ring-Opening of Epoxides with Acetyl Masked Disulfide Nucleophiles.

In the organic or water phase, acetyl masked disulfide nucleophiles were used as the disulfide source to react with a wide range of epoxides, affording various β-acetoxy or β-hydroxyl disulfides in good yields with high regioselectivity. This method features transition-metal-free, simple experimental conditions, high atom economy, and scalable potential, which make it attractive and practical.

Total Synthesis of the Pyrrole Alkaloids Strychnuxinal and Strychnuxin

AbstractThe first asymmetric total syntheses of the fused-pyrrole alkaloids strychnuxinal and strychnuxin have been achieved in 6 and 7 steps, respectively, starting from commercially available (±)-4-chlorostyrene oxide. Key steps in the synthetic route include a regioselective epoxide opening, a reductive etherification sequence to form the central 1,4-oxazine ring, and a late-stage phenol synthesis using a mild palladium-catalyzed coupling reaction. Notably, the optimized synthetic sequence presented avoids the use of traditional protecting groups. Total synthesis of these two structurally related natural products confirmed both their constitution (via NMR and X-ray crystallography) and their absolute configuration (via optical rotation).

Synthetic Studies toward the C1–C12 Fragment of Amphidinolide U

AbstractAmphidinolide U is a cytotoxic marine macrolide isolated from Amphidinium sp., sharing 75% of the amphidinolide C backbone. We report here a synthetic study of the C1–C12 fragment of amphidinolide U. The C6–C12 pattern was built using consecutive regioselective ring opening of epoxides, a directed reaction to control newly formed stereogenic centers. In parallel, the C1–C5 moiety was constructed by taking advantage of a symmetrical diol. Attempts to cross-couple the C1–C5 and C6–C12 fragments by using a Suzuki cross-coupling reaction led to poor conversion rates. The same transformation on a close substrate model used during past studies on the total synthesis of amphidinolides F and C2 was successful. These contrasting results could be explained by a presumed steric hindrance of the protecting group adjacent to the vinyl function involved in the cross-coupling reaction. Our investigations will stimulate the optimization of C(sp2)–C(sp3) cross-coupling reactions with bulky substrates, with the aim of achieving a total synthesis of amphidinolide U.

Stereoselective total synthesis of Pestalotioprolide C and C7-epi-Pestalotioprolide C

The total synthesis of 14 membered macrolide Pestalotioprolide C and C7-epi- Pestalotioprolide C were accomplished starting from commercially available D-Mannitol by Stereoselective synthetic approach. The key reactions involved are Mitsunobu reaction, Regioselective ring opening of chiral epoxide and ring-closing metathesis reactions (RCM).

BF3/HY as a microporous solid acid catalyst for regioselective ring-opening of epoxides

A solid acid catalyst BF3/HY was synthesized and used for regioselective ring-opening of epoxides; different aldehydes could be obtained with exceptional yields and selectivity.

Ruthenium-Catalyzed Reductive Coupling of Epoxides with Primary Alcohols via Hydrogen Transfer Catalysis

Herein, we report the ruthenium-catalyzed synthesis of β-alkylated secondary alcohols via the regioselective ring-opening of epoxides with feedstock primary alcohols. The reaction utilized alcohol as the carbon source and the terminal reductant. Kinetic and labeling experiments elucidate the hydrogen transfer catalysis that operates via tandem Markovnikov selective transfer hydrogenation of terminal epoxides and hydrogen transfer-mediated cross-coupling of the resulting alcohol with primary alcohol substrates. A broad scope (40 examples including drugs/natural product derivatives) and excellent regioselectivity for a variety of substrates were shown.

Calcium(II)‐Catalyzed Chemoselective and Regioselective Epoxide Ring Opening with NH Sulfoximines

AbstractWe describe herein a versatile methodology for the synthesis of 1,2‐sulfoximidoyl ethanols thanks to a Ca(NTf2)2‐catalyzed epoxide ring‐opening with NH sulfoximines in 2‐MeTHF at 90 °C. The reaction is regioselective by an attack on the less hindered position of the epoxides. The chemoselectivity is assessed by competition reactions with other nucleophiles.

Green Reductive Regioselective Opening of Epoxides: A Green Chemistry Laboratory Experiment

Green chemistry is finding its place as one of the most essential study topics in the curriculum of future chemists and chemical engineers. Experiments that meet green chemistry principles contribute to make the laboratory a safer working place, generate less waste, and allow students to increase their knowledge in new environmentally friendly chemical methodologies. The work reported here focuses on the reductive opening of epoxides to afford the less substituted alcohols, which can be carried out at room temperature under catalytic conditions and using water as a hydrogen atom source. The results of this work, as well as a procedure which allows the initiation of students in the application of green chemistry techniques through a particular example, are reported. This laboratory practice can be used to teach organic and radical chemistry, green chemistry principles, and product analysis (thin layer chromatography, flash chromatography, 1H NMR spectroscopy, and IR spectroscopy).

Pd/Et3N·HI-Catalyzed Intramolecular C-H Alkylation to Access [a]-Annulated Indoles via Highly Regioselective Ring-Opening of Epoxides.

A Pd/Et3N·HI-catalyzed intramolecular C-H alkylation of indoles with epoxides was achieved to furnish N-fused indole frameworks (5-, 6-, and 7-membered rings) bearing an alcohol group. The conversion proceeded smoothly in the presence of a catalytic amount of Et3N·HI together with a palladium catalyst and exhibited great functional group tolerance. The employment of Et3N·HI not only avoids the prior preparation of alkyl halide substrates but also is the key to the high chemoselective ring-opening of epoxides. Preliminary mechanism explorations strongly support a radical pathway, and the catalytic cycle was established tentatively according to the mechanism investigation experiments.

Catalytic reductive ring opening of epoxides enabled by zirconocene and photoredox catalysis

Catalytic reductive ring opening of epoxides enabled by zirconocene and photoredox catalysis

Chemoenzymatic Synthesis of the Most Pleasant Stereoisomer of Jessemal.

We describe the asymmetric synthesis of the most pleasant enantiomer of Jessemal fragrance. The key steps are (i) the one-pot reduction of an α-chloro-tetrasubstituted cyclohexenone to give the chlorohydrin, catalyzed by two stereoselective redox enzymes (an ene-reductase and an alcohol dehydrogenase); (ii) the regioselective epoxide ring-opening with organocuprate or organolithium nucleophiles. Density functional theory calculations together with the Curtin–Hammett principle allowed the rationalization of the regioselectivity.

Regioselective ring-opening of epoxides towards Markovnikov alcohols: a metal-free catalytic approach using abnormal N-heterocyclic carbene.

Herein we report the first metal-free regioselective Markovnikov ring-opening of epoxides (selectivity up to 99%) using an abnormal N-heterocyclic carbene (aNHC) to yield secondary alcohols. DFT calculations and X-ray crystallography suggest that the Markovnikov selectivity originates from the high nucleophilicity and steric factors associated with the aNHC.

PH-controlled regioselective nucleophilic ring-opening of epoxide: an improved process for the preparation of (R)-(-)- or (S)-(+)-3-hydroxytetrahydrofuran.

An environmentally benign, cost-effective and scalable process for the preparation of both the enantiomers of 3-hydroxytetrahydrofuran has been developed. pH-Controlled ring opening of enantiomerically pure epichlorohydrins with cyanohydrin is the key step of the process. The entire protocol does not require any column purification.

Synergistic effect of GO/SrFe12O19 as magnetic hybrid nanocatalyst for regioselective ring-opening of epoxides with amines under eco-friendly conditions.

Herein, a highly efficient magnetically separable hybrid GO/SrFe12O19 nanocomposite was synthesized via dispersing M-type strontium hexaferrite (SrFe12O19) on graphene oxide (GO) sheets. First, SrFe12O19 nanoparticles (NPs) and GO sheets were prepared via chemical coprecipitation and chemical oxidation of graphite powder, respectively. Chemically reduced GO (rGO) and rGO/SrFe12O19 were also prepared for comparison purposes. Thereafter, the prepared nanostructured materials were explored by XRD, FTIR, FESEM-EDX, BET, and Zetasizer analyses. All the characterizations confirm the nanoscale and the high stability structures of the prepared materials. The prepared hybrid magnetic nanocomposite GO/SrFe12O19 exhibited a high surface area value resulting in a high catalytic activity and selectivity for the epoxide ring-opening with amines in neat water. The use of hybrid GO/SrFe12O19 compared with pure SrFe12O19 and GO sheets is of great interest for using environmentally benign heterogeneous nanocatalysts, for the synthesis of β-amino alcohols, with excellent recyclability under eco-friendly conditions. Moreover, a mechanistic study was performed through density functional theory (DFT) calculations and Parr functions to explain the observed reactivity and selectivity of SrFe-GO catalyst in the epoxide ring-opening reactions.

Total Synthesis of Citreochlorol Monochloro Analogues via a Catalytically Enantioselective Carbonyl Allylation

AbstractAn efficient synthetic route to citreochlorol analogues, halogenated polyketide secondary metabolites, is described. The key features are Krische’s enantioselective carbonyl allylation, IBr-promoted cyclization, and regioselective epoxide opening. The importance of the route lies in accessing a versatile epoxy ether that enables the formation of citreochlorol monochloro derivatives.

Two (Chemo)-Enzymatic Cascades for the Production of Opposite Enantiomers of Chiral Azidoalcohols

Multi-step cascade reactions have gained increasing attention in the biocatalysis field in recent years. In particular, multi-enzymatic cascades can achieve high molecular complexity without workup of reaction intermediates thanks to the enzymes’ intrinsic selectivity; and where enzymes fall short, organo- or metal catalysts can further expand the range of possible synthetic routes. Here, we present two enantiocomplementary (chemo)-enzymatic cascades composed of either a styrene monooxygenase (StyAB) or the Shi epoxidation catalyst for enantioselective alkene epoxidation in the first step, coupled with a halohydrin dehalogenase (HHDH)-catalysed regioselective epoxide ring opening in the second step for the synthesis of chiral aliphatic non-terminal azidoalcohols. Through the controlled formation of two new stereocenters, corresponding azidoalcohol products could be obtained with high regioselectivity and excellent enantioselectivity (99% ee) in the StyAB-HHDH cascade, while product enantiomeric excesses in the Shi-HHDH cascade ranged between 56 and 61%.