Lewis Acid Catalyzed Ring Opening Research Articles

Lewis Acid-Catalyzed Ring-Opening Cross-Coupling Reaction of gem-Difluorinated Cyclopropanes Enabled by C-F Bond Activation.

gem-Difluorinated cyclopropanes have attracted wide research interest in organic synthesis due to their high reactivity. Herein, we report a Lewis acid-catalyzed cross-coupling reaction of mono- and disubstituted gem-difluorinated cyclopropanes with nucleophiles. The formation of a fluoroallyl cation species triggered via the Lewis acid-assisted activation of the C-F bond is proposed in this transformation. The cation species is then trapped by the nucleophiles, including electron-rich arenes and allylsilanes, to deliver a series of fluoroallylic products in good yields. The reaction provides an alternative mode for using gem-difluorinated cyclopropanes as fluoroallyl surrogates.

Synthesis of chiral β-substituted γ-amino-butyric acid derivativesviaenantioconvergent ring opening of racemic 2-(hetero)aryl aziridines with ketene silyl acetals

Lewis acid-catalyzed enantioconvergent ring opening of racemic 2-(hetero)aryl-N-sulfonyl aziridines with ketene silyl acetals is developed.

Lewis Acid Catalyzed Nucleophilic Ring Opening and 1,3-Bisfunctionalization of Donor-Acceptor Cyclopropanes with Hydroperoxides: Access to Highly Functionalized Peroxy/(α-Heteroatom Substituted)Peroxy Compounds.

The Lewis acid catalyzed ring opening reaction of Donor-Acceptor (D-A) cyclopropanes with alkyl hydroperoxides is reported to furnish various peroxycarbonyls and 1,3-haloperoxygenated compounds in good to excellent yields. This method adds another instance to scarcely reported noncyclilizing 1,3-bisfunctionalization of D-A cyclopropanes with two different functional groups and relies on the dual role of peroxide as nucleophile and oxidant through an orchestrated reaction sequence. The products obtained, including α-heterosubstituted peroxy compounds, are amenable to useful synthetic elaboration.

Mechanism of Regioselective Ring-Opening Reactions of 1,2-Epoxyoctane Catalyzed by Tris(pentafluorophenyl)borane: A Combined Experimental, Density Functional Theory, and Microkinetic Study

A nonconventional, water-mediated catalytic mechanism was proposed to explain the effects of residual water on the reactivity and regioselectivity of tris(pentafluorophenyl)borane catalyst in the ring-opening reaction of 1,2-epoxyoctane by 2-propanol. This nonconventional mechanism was proposed to operate in parallel with conventional Lewis acid-catalyzed ring-opening. Microkinetic modeling was conducted to validate the proposed reaction mechanism, with all kinetic and thermodynamic parameters derived from density functional theory (DFT) calculations. Experimental data at a variety of temperatures and water contents were captured by the model after adjustments within reasonable limits set by experimental benchmarking and accuracy of theory of a small subset of parameters. In addition, the microkinetic model was able to generate accurate predictions at reaction conditions that were not used for parameter estimation. Detailed analysis of the net reaction rates showed that >95% of the reaction flux passed through conventional Lewis-acid pathways at water levels <500 ppm, even though the borane-epoxide adduct never accounted for more than 30% of the catalyst speciation under reaction conditions. With increasing water, as much as 80% of the reaction flux utilized water-mediated reaction intermediates. Within the water-mediated mechanisms, different hydrogen bond acceptors (HBAs) influenced the reaction regioselectivity. Overall, this validated mechanism and microkinetic model provided better understanding of industrially important ring-opening catalysis with this catalyst in the presence of water and could facilitate future improvement of catalyst regioselectivity and reactivity.

Synthesis of Nonracemic 1,4-Benzoxazines via Ring Opening/Cyclization of Activated Aziridines with 2-Halophenols: Formal Synthesis of Levofloxacin.

Novel 3,4-dihydro-1,4-benzoxazine derivatives have been synthesized by an efficient and simple method in excellent enantio- and diastereospecificity (ee > 99%, de > 99%). The reaction proceeds via Lewis acid-catalyzed SN2-type ring opening of activated aziridines with 2-halophenols followed by Cu(I)-catalyzed intramolecular C-N cyclization in a stepwise fashion under one-pot conditions to furnish the 3,4-dihydro-1,4-benzoxazine derivatives in excellent yields (up to 95%). The strategy offers a short and efficient synthesis to ( S)-3-methyl-1,4-benzoxazine ( S)-3v, a late stage intermediate in the synthesis of levofloxacin.

Stereoselective synthesis of 3-spiropiperidino indolenines via SN2-type ring opening of activated aziridines with 1H-indoles/Pd-catalyzed spirocyclization with propargyl carbonates.

3-Spiropiperidino indolenines have been synthesized via novel Lewis acid-catalyzed SN2-type ring opening of activated aziridines with 1H-indoles followed by Pd-catalyzed dearomative spirocyclization with propargyl carbonates in up to 88% yields. The step and pot-economic transformation comprises sequential C-C, C-N, and C-C bond forming steps generating two stereogenic centers including an all-carbon quaternary stereocenter to furnish the products in diastereomerically pure (dr >99 : 1) forms with excellent enantiomeric excess (ee up to >99%). The synthetic versatility of the strategy has been illustrated by converting the synthesized products into spirocyclic indolenine 2-piperidinones, dihydropiperidines, and 5-alkynylated piperidines.

Domino Ring-Opening Cyclization of Activated Aziridines with Indoles: Synthesis of Chiral Hexahydropyrroloindoles.

A highly enantioselective synthetic route to hexahydropyrrolo[2,3-b]indoles via Lewis acid-catalyzed SN2-type ring opening of activated aziridines with indoles having substitutions at 3- and other positions followed by cyclization in a domino fashion has been developed. Hexahydropyrrolo[2,3-b]indoles have been detosylated in the same pot to afford the corresponding products with free NH group in excellent yields (up to 95%) and enantioselectivity (up to >99%).

Lewis Acid and (Hypo)iodite Relay Catalysis Allows a Strategy for the Synthesis of Polysubstituted Azetidines and Tetrahydroquinolines.

A catalytic [3 + 1]-annulation reaction between cyclopropane 1,1-diester and aromatic amine is developed based on the relay catalysis strategy. Lewis acid-catalyzed nucleophilic ring opening of cyclopropane 1,1-diester with aromatic amine and (hypo)iodite-catalyzed C-N bond formation are combined successfully in one reaction. Using this reaction, biologically important azetidines and tetrahydroquinolines can be prepared directly.

A Facile, Six-Step Process for the Synthesis of (3S,5S)-3-Isopropyl-5-((2S,4S)-4-isopropyl-5-oxo-tetrahydrofuran-2-yl)-2-oxopyrrolidine-1-carboxylic Acid tert-Butyl Ester, The Key Synthetic Intermediate of Aliskiren

A facile, six-step process for the synthesis of (3S,5S)-3-isopropyl-5-((2S,4S)-4-isopropyl-5-oxotetrahydro- furan-2-yl)-2-oxopyrrolidine-1-carboxylic acid tert-butyl ester from (S)-4-benzyloxazolidin-2-one 2 in an overall 50% yield is reported. The key transformations include: a highly efficient diastereoselective epoxidation, Lewis acid-catalyzed ring-opening with bromide, an SN2 reaction using NaN3, and a tandem reduction–cyclization reaction.

FeCl3-catalyzed tandem Prins and Friedel–Crafts cyclization: a highly diastereoselective route to polycyclic ring structures

Catalytic FeCl3 in the presence of 4Å molecular sieves has been shown to effect highly diastereoselective tandem Prins and Friedel–Crafts cyclization of substituted (E/Z)-6-phenylhex-3-en-1-ol and a variety of aldehydes to provide a range of polycyclic compounds in good to excellent yields. The reaction of an enantioenriched alcohol with an aldehyde provided the cyclization product without loss of optical activity. Furthermore, a Lewis acid catalyzed ring opening resulted in functionalized tetralin derivatives with multiple chiral centers.

A facile synthetic route to 2-trifluoromethyl-substituted polyfunctionalized chromenes and chromones

A method for the preparation of methyl 4-hydroxy-2-(trifluoromethyl)-4 H-chromenes-3-carboxylate derivatives 3a– j from readily available trifluoromethylated building block methyl (Z)-2-bromo-4,4,4-trifluoro-2-butenoate 1 was described. Treatment of 3a– j with Sarrett reagent in CH 2Cl 2 generated methyl 4-oxo-2-(trifluoromethyl)-chromene-3-carboxylate derivatives 4a– h with moderate to good yields, which can be converted to 2-trifluoromethyl-substituted multifunctional benzoxepins through cyclopropanation and Lewis acid-catalyzed ring opening.

Lewis acid-catalyzed nucleophilic ring-opening/intramolecular Conia-ene reactions of methylenecyclopropane 1,1-diesters with propargyl alcohols

We presented a Lewis acid-catalyzed nucleophilic ring opening of methylenecyclopropane (MCP) 1,1-diesters with propargyl alcohols. Unlike the proximal-bond cleavage mode observed in cases of unactivated MCPs, the intrinsic characteristic of MCP 1,1-diesters gave a regiospecific distal-bond cleavage under attack of propargyl alcohols as nucleophiles. By combining a subsequent intramolecular Conia-ene reaction, 3,5-dimethylenetetrahydropyrans could be obtained in either a stepwise or a one-pot strategy.

Soy-based UV-curable thiol–ene coatings

Novel soy-based thiols and enes were synthesized and characterized. Then, soy-based thiol–ene UV-curable coatings were formulated and their coating physiochemical properties were investigated in detail. The use of biorenewable resources, combined with environmentally friendly UV-curable technology, provides a “green + green” solution to the stricter regulations in the coatings industry. Novel soy-based thiols and enes were synthesized through the Lewis acid-catalyzed ring opening reaction of epoxidized soybean oil with multifunctional thiols or hydroxyl functional allyl compounds. FTIR and NMR confirmed the formation of the target compounds. The soy-based thiols and enes were formulated with petrochemical-based enes and thiols, respectively, to make thiol–ene UV-curable coatings. Typical coating film properties, thermal properties, and photopolymerization kinetics of these coatings were studied. Soy-based thiol–ene coatings having lower functionality thiols and enes have poor UV curability and coating properties, which was attributed to the lower crosslink density. Soy-based thiols and enes with higher functionality can be UV-cured in combination with petrochemical-based enes or thiols even without the presence of free radical photoinitiators. Better coating film properties were obtained from these higher functionality thiol–ene systems that were toughened by commercial hyperbranched acrylates.

Synthesis of Tetrahydropyrans from Propargyl Alcohols and 1,1-Cyclopropanediesters: A One-Pot Ring-Opening/Conia-ene Protocol

Lewis acid catalyzed ring opening of 1,1-cyclopropanediesters by the hydroxyl group of a propargyl alcohol sets up a subsequent Conia-ene cyclization to afford substituted tetrahydropyrans in a one-pot, high-yielding procedure.

A Mild Procedure for the Lewis Acid-Catalyzed Ring-Opening of Activated Cyclopropanes with Amine Nucleophiles

The Lewis acid-catalyzed ring-opening of methyl 1-nitrocyclopropanecarboxylates with amine nucleophiles is described. The reaction proceeds at room temperature and with complete preservation of the enantiomeric purity from the electrophilic center of the cyclopropane to the acyclic product. The methodology was applied in an enantioselective synthesis of the dual serotonin/norepinephrine reuptake inhibitor (3R)-3-(1 H-indol-1-yl)- N-methyl-3-phenylpropan-1-amine.

A New Perspective in the Lewis Acid Catalyzed Ring Opening of Epoxides. Theoretical Study of Some Complexes of Methanol, Acetic Acid, Dimethyl Ether, Diethyl Ether, and Ethylene Oxide with Boron Trifluoride

Several 1:1, 1:2, and 2:2 complexes between BF3 and CH3OH (Met), CH3COOH (AcA), (CH3)2O (DME), (CH3CH2)2O (DEE), and (CH2)2O (EOX) have been studied using ab initio (MP2) and density functional theory (DFT) (PBE, B3LYP) methods and the 6-311++G(3df,2pd) basis set. Geometrical structures and vibrational frequencies are reported, in most cases, for the first time. A detailed comparison of the vibrational frequencies for the O...BF3 vibrational modes, as well as for the nu(OH) band in the methanol and acetic acid complexes with BF3, is performed, and the theoretical frequency shifts are compared with the available experimental information. Thermochemical properties are calculated by employing counterpoise correction to alleviate the basis set superposition error. The DFT enthalpy of complexation of the 1:1 complexes results in the order of stability (AcA)2>AcA:BF3>DEE:BF3>DME:BF3>Met:BF3>EOX:BF3>(Met)2; in contrast, MP2 shows the noticeable difference that the AcA:BF3 complex is much less stable (similar to Met:BF3). The order of stability shows that, even though acetic acid prefers dimerization to complexation with BF3, the case is exactly the opposite for methanol. In both cases, the interaction of BF3 with the dimer gives rise to very stable trimers. However, in contrast to the interaction of BF3 with the methanol dimer being stronger than that with the monomer, the interaction of BF3 with the acetic acid dimer is weaker than that with the monomer. The relative strength of the complexes, discussed in the context of BF3-catalyzed ring opening of epoxides, suggests that the effect of the catalyst in a nonprotogenic solvent should be more properly ascribed to activation of the nucleophile instead of activation of the epoxide.

A Convenient Synthetic Route to Tetrahydropyran‐Based Liquid Crystals

AbstractThe tetrahydropyran moiety has been identified as a highly advantageous addition to the toolbox for the design of nematic liquid crystals for LCD applications. A new synthetic procedure based on the Lewis acid catalysed ring opening of oxetanes by lithium iminoenolates followed by reductive dehydroxylation of the resulting hemiketal provides a convenient preparative access to this class of materials.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)

Efficient One‐Pot Ring‐Opening/Aldol Reactions Using (Cyclopropyl)methylstannanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient one-pot ring-opening/aldol reactions using (cyclopropyl)methylstannanes

(Cyclopropyl)methylstannanes, substituted with an electron-withdrawing group, have been found to be effective homoallylating reagents of aldehydes and ketones. The reaction proceeds by Lewis-acid catalyzed ring opening, followed by an aldol condensation of the resulting enolate, providing homoallylation products in excellent yields. The diastereoselectivity of the process was found to be highly dependent upon the temperature and the solvent, the reaction giving mainly anti adducts at −78 °C and syn compounds at 0 °C.

Transition Metal Based Lewis Acid Catalyzed Ring Opening of Epoxides Using Amines under Solvent‐Free Conditions.

AbstractFor Abstract see ChemInform Abstract in Full Text.