Alkylation Of Silyl Enol Ethers Research Articles

Visible light/copper catalysis enabled alkylation of silyl enol ethers with arylsulfonium salts.

An efficient protocol has been developed herein for the site-selective alkylation of silyl enol ethers with arylsulfonium salts giving access to valuable aryl alkyl thioethers under visible light conditions. Enabled by copper (I) photocatalysis, the C-S bond of arylsulfonium salts can be selectively cleaved to deliver C-centered radicals under mild conditions. This developed method provides a straightforward approach to utilize arylsulfonium salts as sulfur sources for the synthesis of aryl alkyl thioethers.

N,N'-Diaryldihydrophenazines as a Sustainable and Cost-Effective Alternative to Precious Metal Complexes in the Photoredox-Catalyzed Alkylation of Aryl Alkyl Ketones.

An inexpensive and highly efficient metal-free alternative to commonly used Ru- and Ir-based catalysts was proposed. It was shown that the new 2,7-di-tert-butyl-5,10-bis(4-trifluoromethylphenyl)-5,10-dihydrophenazine outcompeted the iridium phenylpyridyl complex in photoredox activity in the alkylation of silyl enol ethers yielding aryl alkyl ketones. The reaction occurred under visible light irradiation at room temperature and was also applicable to drug derivatives (ibuprofen and naproxen). In-depth photophysical, electrochemical, and quantum chemical studies showed that the aforementioned N,N-diaryldihydrophenazine exhibited enhanced properties that were essential for the photoredox catalysis (a long-lived triplet excited state, strong reducing ability, high stability of the radical cations formed in single-electron-transfer event, and chemical inertness of the catalyst with respect to reactants). Importantly, the substituted N,N'-diaryldihydrophenazines could be obtained directly from diaryl amines; a facile, easily handled and scaled-up one-pot synthetic procedure was elaborated.

Photocatalytic decarboxylative alkylation of silyl enol ether and enamide with N-(acyloxy)phthalimide using ammonium iodide

Under visible light, a catalytic amount of ammonium iodide promotes the decarboxylative alkylation of silyl enol ether and enamide with aliphatic N-(acyloxy)phthalimide through the photoactivation of a transiently assembled chromophore.

Copper-Catalyzed Alkylation of Silyl Enol Ethers with Sterically Hindered α-Bromocarbonyls: Access to the Histamine H3 Receptor Antagonist.

A general and efficient copper-catalyzed alkylation of silyl enol ethers with functionalized alkyl bromides has been developed for the synthesis of the sterically hindered γ-ketoesters. The transformation was induced through C(sp3)-halogen activation of commercially available sterically hindered alkyl bromides under mild conditions in good results. The strategy could be used for the synthesis of biologically active histamine H3 receptor (H3R) antagonist for medicinal purposes.

Palladium-Catalyzed Dual Ligand-Enabled Alkylation of Silyl Enol Ether and Enamide under Irradiation: Scope, Mechanism, and Theoretical Elucidation of Hybrid Alkyl Pd(I)-Radical Species

We report herein that a palladium catalyst in combination with a dual phosphine ligand system catalyzes alkylation of silyl enol ether and enamide with a broad scope of tertiary, secondary, and pri...

Photocatalytic decarboxylative alkylations mediated by triphenylphosphine and sodium iodide.

Most photoredox catalysts in current use are precious metal complexes or synthetically elaborate organic dyes, the cost of which can impede their application for large-scale industrial processes. We found that a combination of triphenylphosphine and sodium iodide under 456-nanometer irradiation by blue light-emitting diodes can catalyze the alkylation of silyl enol ethers by decarboxylative coupling with redox-active esters in the absence of transition metals. Deaminative alkylation using Katritzky's N-alkylpyridinium salts and trifluoromethylation using Togni's reagent are also demonstrated. Moreover, the phosphine/iodide-based photoredox system catalyzes Minisci-type alkylation of N-heterocycles and can operate in tandem with chiral phosphoric acids to achieve high enantioselectivity in this reaction.

Photoredox-Catalyzed Decarboxylative Alkylation of Silyl Enol Ethers To Synthesize Functionalized Aryl Alkyl Ketones.

Photoredox-catalyzed decarboxylative alkylation of silyl enol ethers has been developed. Diverse functionalized aryl alkyl ketones were afforded in modest to good yields using N-(acyloxy)phthalimide as an easy access alkyl radical source under mild and operationally simple conditions. The excellent performance of drug molecules such as fenbufen and indomethacin and naturally occurring carboxylic acids such as stearic acid and dehydrocholic acid further demonstrated the practicability of the reaction.

Electrophilic Activation of Iodonium Ylides by Halogen‐Bond‐Donor Catalysis for Cross‐Enolate Coupling

AbstractThe umpolung alkylation of silyl enol ethers with an iodonium(III) ylide proceeds under mild conditions to afford various 1,4‐dicarbonyl compounds in high yields in the presence of a halogen‐bonding catalyst. Unlike typical transition‐metal activation processes of such ylide precursors, which tend to proceed via carbenoid intermediates, experimental and computational studies indicate that halogen bonding (XB) between the XB donor catalyst and the iodonium ylide plays a crucial role in promoting the reaction. The identification of a compatible Bronsted base catalyst enabled the extension of this method to enols generated in situ to give the corresponding adducts in good yields.

Electrophilic Activation of Iodonium Ylides by Halogen-Bond-Donor Catalysis for Cross-Enolate Coupling.

The umpolung alkylation of silyl enol ethers with an iodonium(III) ylide proceeds under mild conditions to afford various 1,4-dicarbonyl compounds in high yields in the presence of a halogen-bonding catalyst. Unlike typical transition-metal activation processes of such ylide precursors, which tend to proceed via carbenoid intermediates, experimental and computational studies indicate that halogen bonding (XB) between the XB donor catalyst and the iodonium ylide plays a crucial role in promoting the reaction. The identification of a compatible Bronsted base catalyst enabled the extension of this method to enols generated in situ to give the corresponding adducts in good yields.

ChemInform Abstract: Synthesis and Exploration of Electronically Modified (R)‐5,5‐Dimethyl‐(p‐CF3)3‐i‐PrPHOX in Palladium‐Catalyzed Enantio‐ and Diastereoselective Allylic Alkylation: A Practical Alternative to (R)‐(p‐CF3)3‐t‐BuPHOX.

AbstractIt is demonstrated, that the novel phosphinooxazoline derivative (PHX) is an efficient ligand for the enantioselective allylic alkylation of silyl enol ether (I) and the diastereoselective decarboxylative allylic alkylation of the β‐ketoester (IV).

ChemInform Abstract: Highly Enantioselective Synthesis of 3‐Substituted Furanones by Palladium‐Catalyzed Kinetic Resolution of Unsymmetrical Allyl Acetates.

The Pd-catalyzed asymmetric allylic alkylation (AAA) holds a prominent position among the most versatile methods for C C bond formation that are widely applied in natural product synthesis. This transformation typically features broad functional group tolerance and excellent regioand enantioselectivity. In particular, Pd-catalyzed kinetic resolutions of symmetrical allylic substrates and dynamic kinetic transformations have been developed recently, which extends their potential in synthetic chemistry. However, Pd-catalyzed kinetic resolutions of unsymmetrical acyclic allylic substrates with high yield and enantioselectivity are rare. Furthermore, the enantioselective allylic alkylation of silyl enol ethers is still a challenging reaction. Graening and Hartwig reported a highly enantioselective alkylation of monosubstituted allylic substrates with silyl enol ethers catalyzed by an Ir complex. Although excellent results of allylic alkylations have been reported with enolates that are preformed or generated in situ, to the best of our knowledge, Pd-catalyzed AAAwith a nonstabilized silyl enol ether as nucleophile remains an elusive goal (Scheme 1). Herein, we present the Pd-catalyzed kinetic resolution of 1,3-disubstituted unsymmetrical allylic substrates with nonstabilized silyl enol ethers as nucleophiles, which provides a highly regioand enantioselective synthesis of 3-substituted g-butenolides. The g-butyrolactone skeleton is present in more than 13000 natural products, which have attracted considerable attention because of the range of important biological activities associated with this class of compounds. As part of our program to develop catalytic enantioselective methods to access optically active g-butenolides and lactones, we envisioned the possibility of using 2-trimethylsilyloxyfuran (TMSOF) as nucleophile in a Pd-catalyzed AAA reaction. Initially, we examined the allylic substitution of carbonate 1a by utilizing TMSOFas nucleophile and a chiral Pd catalyst based on Trost Ligand L1 (Table 1, entry 1). The 3-substituted product 3 and 5-substituted product 4 were obtained in a 2:1 ratio and in 36% ee for product 3 (Table 1, entry 1). Using a lower temperature (0 8C), the ee value only slightly increased (49% ee, Table 1, entry 2). With tert-butyl carbonate as the leaving group, the regioselectivity shifted in favor of the formation of the 5-substituted product (3/4= 1:2, Table 1,

Highly Enantioselective Synthesis of 3‐Substituted Furanones by Palladium‐Catalyzed Kinetic Resolution of Unsymmetrical Allyl Acetates

The Pd-catalyzed asymmetric allylic alkylation (AAA) holds a prominent position among the most versatile methods for C C bond formation that are widely applied in natural product synthesis. This transformation typically features broad functional group tolerance and excellent regioand enantioselectivity. In particular, Pd-catalyzed kinetic resolutions of symmetrical allylic substrates and dynamic kinetic transformations have been developed recently, which extends their potential in synthetic chemistry. However, Pd-catalyzed kinetic resolutions of unsymmetrical acyclic allylic substrates with high yield and enantioselectivity are rare. Furthermore, the enantioselective allylic alkylation of silyl enol ethers is still a challenging reaction. Graening and Hartwig reported a highly enantioselective alkylation of monosubstituted allylic substrates with silyl enol ethers catalyzed by an Ir complex. Although excellent results of allylic alkylations have been reported with enolates that are preformed or generated in situ, to the best of our knowledge, Pd-catalyzed AAAwith a nonstabilized silyl enol ether as nucleophile remains an elusive goal (Scheme 1). Herein, we present the Pd-catalyzed kinetic resolution of 1,3-disubstituted unsymmetrical allylic substrates with nonstabilized silyl enol ethers as nucleophiles, which provides a highly regioand enantioselective synthesis of 3-substituted g-butenolides. The g-butyrolactone skeleton is present in more than 13000 natural products, which have attracted considerable attention because of the range of important biological activities associated with this class of compounds. As part of our program to develop catalytic enantioselective methods to access optically active g-butenolides and lactones, we envisioned the possibility of using 2-trimethylsilyloxyfuran (TMSOF) as nucleophile in a Pd-catalyzed AAA reaction. Initially, we examined the allylic substitution of carbonate 1a by utilizing TMSOFas nucleophile and a chiral Pd catalyst based on Trost Ligand L1 (Table 1, entry 1). The 3-substituted product 3 and 5-substituted product 4 were obtained in a 2:1 ratio and in 36% ee for product 3 (Table 1, entry 1). Using a lower temperature (0 8C), the ee value only slightly increased (49% ee, Table 1, entry 2). With tert-butyl carbonate as the leaving group, the regioselectivity shifted in favor of the formation of the 5-substituted product (3/4= 1:2, Table 1,

Titanium silicates as efficient catalyst for alkylation and acylation of silyl enol ethers under liquid-phase conditions

The activity of titanium- and tin-silicate samples such as TS-1, TS-2, Ti-β and Sn-MFI has been investigated for acylation and alkylation of silyl enol ethers under mild liquid-phase conditions. Silyl enol ethers successfully react with acetyl chloride and tert-butyl chloride under dry conditions in the presence of above catalysts to produce the corresponding acylated and alkylated products, respectively. In the case of acetylation reaction, two different nucleophiles with carbon-center (C-atom) and oxygen-center (O-atom) in silyloxy group of silyl enol ether reacts with acetyl chloride to give 1,3-diketone and ketene-ester, respectively. The selectivity for alkylation is always ca. 100% and no side products are formed. Among the various solvents investigated, anhydrous THF was found to be the suitable solvent for alkylation; whereas dichloromethane exhibited high selectivity for diketones for acylation. The formation of nucleophiles from silyl enol ethers appears to be the key step for successful acetylation and tert-butylation by nucleophilic reaction mechanism. Sn-MFI showed less activity than that observed over the titanosilicates. The observed catalytic activity is explained on the basis of “oxophilic Lewis acidity” of titanium silicate molecular sieves in the absence of H 2O under dry reaction conditions.

Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

Unprecedented alkylation of silyl enol ethers has been developed by the use of ortho-alkynylbenzoic acid alkyl esters as alkylating agents in the presence of a gold catalyst. The reaction probably proceeds through the gold-induced in situ construction of leaving groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regenerate the silyl enol ether structure.

ChemInform Abstract: The Alkylation of Silyl Enol Ethers with SN1-Unreactive Iodides in the Presence of Silver Trifluoroacetate.

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Chemo- and diastereoselective Bi(OTf) 3-catalyzed benzylation of silyl nucleophiles

The direct alkylation of silyl enol ethers with para-methoxybenzylic alcohols or their corresponding acetates was efficiently catalyzed by Bi(OTf) 3 in CH 3NO 2 as the solvent. The reaction provided the α-benzylated carbonyl compounds in high yields after short reaction times using 1–2.5 mol % of the catalyst. Benzylic acetates other than para-methoxybenzylic acetates also underwent the reaction. High facial diastereoselectivities were observed with acetates derived from chiral α-branched para-methoxybenzylic alcohols. In addition, a catalytic reduction with Et 3SiH as the reducing agent is reported.

Cationic Polymerization of Vinyl Ethers in the Presence of Silyl Enol Ethers

AbstractSummary: Vinyl ether oligomers with reactive end groups were prepared by alkylation of silyl enol ethers during propagation. Silyl enol ethers were added to the cationic polymerization of isobutyl vinyl ether, ethyl vinyl ether and methyl vinyl ether. The polymerizations were carried out under non‐living conditions so that, in the absence of added silyl enol ether, MALDI TOF mass spectrometry gave evidence for end groups other than those derived from reaction with the methanol capping agent. Addition of either phenyl‐1‐(trimethylsilyloxy)ethylene or 1‐methoxyphenyl‐1‐(trimethylsilyloxy)ethylene significantly reduced the fraction of end groups derived from intramolecular termination reactions, such as elimination, at temperatures between 21 and −78 °C. However, as in living systems lowering the reaction temperature increased the proportion of chains with the desired chain‐end functionality (i.e. aryl ketone derived from alkylation of the silyl enol ether). α‐β Elimination also produced a population of isobutyl vinyl ether oligomers with α‐β unsaturated ketone end groups.Structure of an oligo(isobutyl vinyl ether) with a substituted phenyl ketone end group.imageStructure of an oligo(isobutyl vinyl ether) with a substituted phenyl ketone end group.

N-Methoxy-N-acylnitrenium Ions: Application to the Formal Synthesis of (±)-Desmethylamino FR901483

[reaction: see text] The formal synthesis of (+/-)-desmethylamino FR901483 (2) is described. Construction of the unique azatricyclic skeleton of 2 was accomplished by a sequence which involved (i) preparation of dienone 7 by an N-methoxy-N-acylnitrenium ion-induced spirocyclization, (ii) formation of 2-azabicyclo[3.3.1]nonane 5 by the 6-(pi-exo)-exo-trig radical cyclization of 1,7-enyne 6, and (iii) installation of the C-5 p-methoxybenzyl side chain by Lewis acid-mediated alkylation of silyl enol ether 18.

Synthesis of Telechelic Oligo(isobutyl vinyl ether)s via Alkylation of Silyl Enol Ethers by the Propagating Chain End in an Ab Initio Cationic Polymerisation

Telechelic oligomers prepared by cationic polymerisation of isobutyl vinyl ether were synthesised by an ab initio procedure, in which silyl enol ethers were alkylated by the propagating carbocationic chain end. In-situ addition of a silyl enol ether to the propagating chain end in a cationic polymerisation yields functionalized oligomers during the polymerisation. Therefore, it is not necessary to operate under living conditions.

The alkylation of silyl enol ethers with S N1-unreactive iodides in the presence of silver trifluoroacetate

Silyl enol ethers can be effectively alkylated with primary n-alkyl iodides in the presence of silver trifluoro-acetate to give monoalkyl ketones.