Alkyl Enol Ethers Research Articles

Alkyl Enol Ethers: Development in Intermolecular Organic Transformation.

Alkyl enol ethers (AEE) are versatile synthetic intermediates with a unique reactivity pattern. This review article summarizes the synthesis of AEE as well as its reactivity and how enol ether undergoes intermolecular reactions for various bond formation, leading to the construction of several useful organic molecules. The synthetic applications of alkyl enol ethers towards intermolecular bond-forming reactions include metal-catalyzed reactions, cycloaddition and heterocycle formation as well as rwactions in the field of natural products synthesis. The achievement of these impressive transformations prove the countless synthetic potential of AEE. The main objective of this review is to bring attentiveness among synthetic chemists to show how AEE extensively can be used to react with both electrophiles as well as nucleophiles, thereby behaving as an ambiphilic reactant. We trust that the unique reactivity pattern of alkyl enol ethers and the fundamental mechanistic idea can attract chemists in AEE chemistry. Exclusively, intermolecular reactions of AEE with other functionalized moieties have not been reviewed to the best of our knowledge.

Chemiluminescence-promoted oxidation of alkyl enol ethers by NHPI under mild conditions and in the dark.

The hydroperoxidation of alkyl enol ethers using N-hydroxyphthalimide and molecular oxygen occurred in the absence of catalyst, initiator, or light. The reaction proceeds through a radical mechanism that is initiated by N-hydroxyphthalimide-promoted autoxidation of the enol ether substrate. The resulting dioxetane products decompose in a chemiluminescent reaction that allows for photochemical activation of N-hydroxyphthalimide in the absence of other light sources.

α-Tertiary Dialkyl Ether Synthesis via Reductive Photocatalytic α-Functionalization of Alkyl Enol Ethers

The photocatalytic construction of C(sp3)-rich α-tertiary dialkyl ethers through the reductive α-functionalization of alkyl enol ether substrates with conjugated alkenes in the presence of a Hantzs...

Cyclisation Reactions Involving Alkyl Enol Ethers

AbstractEnol ethers are a fascinating product class and valuable building blocks with versatile reactivities and synthetic applications. With the emergence of silyl enol ethers, the chemistry of simple alkyl enol ethers has received less attention and targeted reviews of their chemistry are scarce. Especially intramolecular reactions under participation of an enol ether function have never been specifically surveyed. The construction of cyclic scaffolds is arguably one of the most important and challenging tasks of the organic chemist and intramolecular cyclisations represent the most straight‐forward tool to achieve this goal. The potential of enol ether‐containing substrates to form oxygenated carbo‐ and heterocycles is obvious. The purpose of this review is to discuss their particular reactivity and to direct the reader's attention to how their unique properties have been harnessed by organic chemists for the construction of rings.magnified image

Enantioselective Synthesis of Alkyl Allyl Ethers via Palladium-Catalyzed Redox-Relay Heck Alkenylation of O-Alkyl Enol Ethers.

Herein we report a transformation that generates an array of enantiomerically enriched, alkyl allyl ethers. Cyclic, acyclic, and heteroatom-bearing alkenyl triflates undergo an enantioselective, palladium-catalyzed C-C bond formation with diverse acyclic O-alkyl enol ethers in good yields and excellent enantioselectivities.

Visible-Light Photocatalytic Preparation of 1,4-Ketoaldehydes and 1,4-Diketones from α-Bromoketones and Alkyl Enol Ethers.

A Ru2+-photocatalyzed, visible-light-mediated ATRA reaction for the straightforward preparation of 1,4-ketoaldehydes, 1,4-diketones, and 1,4-ketoesters, which are of difficult access by other means, is reported herein. This method employs readily accessible α-bromoketones and alkyl vinyl ethers as starting materials, allowing the construction of secondary, tertiary, and challenging quaternary centers. In addition, the synthetic usefulness of this method is illustrated by applying it to the construction of substituted pyrroles.

Five Roads That Converge at the Cyclic Peroxy-Criegee Intermediates: BF3-Catalyzed Synthesis of β-Hydroperoxy-β-peroxylactones

We have discovered synthetic access to β-hydroperoxy-β-peroxylactones via BF3-catalyzed cyclizations of a variety of acyclic precursors, β-ketoesters and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals, with H2O2. Strikingly, independent of the choice of starting material, these reactions converge at the same β-hydroperoxy-β-peroxylactone products, i.e., the peroxy analogues of the previously elusive cyclic Criegee intermediate of the Baeyer-Villiger reaction. Computed thermodynamic parameters for the formation of the β-hydroperoxy-β-peroxylactones from silyl enol ethers, enol acetates, and cyclic acetals confirm that the β-peroxylactones indeed correspond to a deep energy minimum that connects a variety of the interconverting oxygen-rich species at this combined potential energy surface. The target β-hydroperoxy-β-peroxylactones were synthesized from β-ketoesters, and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals were obtained in 30-96% yields. These reactions proceed under mild conditions and open synthetic access to a broad selection of β-hydroperoxy-β-peroxylactones that are formed selectively even in those cases when alternative oxidation pathways can be expected. These β-peroxylactones are stable and can be useful for further synthetic transformations.

RhII -Catalyzed β-C(sp2 )-H Alkylation of Enol Ethers, Enamides and Enecarbamates with α-Diazo Dicarbonyl Compounds.

A RhII -catalyzed method for intermolecular alkylation of the β-C(sp2 )-H bond of enol ethers, enamides, and enecarbamates with α-diazo-1,3-dicarbonyl compounds is reported. The products are formed in up to 99 % yield and can be readily derivatized under a variety of conditions. By utilizing a combination of experimental and computational studies, the presumptive addition-elimination reaction mechanism was investigated and found to proceed under thermodynamic control at higher temperature. The acquired fundamental knowledge was translated into a strategic reaction design and yielded the first example of the β-C-H functionalizations of acyclic enol ethers using α-diazo-1,3-dicarbonyl compounds.

ChemInform Abstract: Synthesis of Multisubstituted Silyloxy‐Based Donor—Acceptor Cyclobutanes by an Acid‐Catalyzed [2 + 2] Cycloaddition

AbstractReview: [33 refs.

Mechanistic Study of the Asymmetric Carbonyl-Ene Reaction between Alkyl Enol Ethers and Isatin Catalyzed by the N,N'-Dioxide-Mg(OTf)2 Complex.

The mechanism and origin of the stereoselectivity of the asymmetric carbonyl-ene reaction between N-methyl-protected isatin and 2-methyloxypropene catalyzed by the N,N'-dioxide-Mg(OTf)2 complex were investigated by DFT and ONIOM methods. The background reaction occurred via a two-stage, one-step mechanism with a high activation barrier of 30.4 kcal mol(-1) at the B3LYP-D3(BJ)/6-311G**(SMD, CH2Cl2)//B3LYP/6-31G*(SMD, CH2Cl2) level at 303 K. Good linear correlations between the global nucleophilicity index (N) and the activation energy barrier (ΔG(⧧)) were found. The chiral N,N'-Mg(II) complex catalyst could enhance the electrophilicity of the isatin substrate by forming hexacoordinate Mg(II) reactive species. The substituent at the ortho positions of aniline combined with the aliphatic ring of the backbone in the chiral N,N'-dioxide ligand played an important role in the construction of a favorable "pocket-like" chiral environment (chiral pocket) around the Mg(II) center, directing the preferential orientation of the incoming substrate. An unfavorable steric arrangement in the re-face attack pathway translated into a more destabilizing activation strain of the ene substrate, enhancing enantiodifferentiation of two competing pathways for the desired R product. This work also suggested a new phosphine ligand (N-L1) for the formation of the Mg(II) complex catalyst for the asymmetric carbonyl-ene reaction. The chiral environment and Lewis acidity of the Mg(II) complex could be fine-tuned by introduction of P-donor units into the ligand for highly efficient asymmetric catalysis.

Synthesis of Multisubstituted Silyloxy‐based Donor‐Acceptor Cyclobutanes by an Acid‐Catalyzed [2+2] Cycloaddition

AbstractThis account summarizes our recent efforts on the acid‐catalyzed [2+2] cycloaddition of silyl enol ethers with α,β‐unsaturated esters, giving donor‐acceptor (D‐A) cyclobutanes and their related reactions. The cycloaddition generally produces multisubstituted cyclobutanes in good yields with high diastereoselectivity. We found that aluminum Lewis acids and triflic imide (Tf2NH) had good catalytic activity. The retro [2+2] cycloaddition proceeded at higher reaction temperatures, and in some cases, diastereoselectivity switching of cycloadducts was observed. A microflow protocol was established for Tf2NH‐catalyzed [2+2] cycloaddition. Although the cycloaddition usually requires cryogenic conditions in a batch reactor, the microreactor system enabled the production of D‐A cyclobutanes, even at ambient temperature. [2+2] Cycloaddition of allylsilanes and alkyl enol ethers, instead of silyl enol ethers, afforded the corresponding D‐A cyclobutanes.

ChemInform Abstract: Rhodium‐Azavinylcarbene: A Versatile Synthon‐Enabling Divergent Synthesis of Nitrogen Heterocycles

AbstractReview: [19 refs.

Rhodium-Azavinylcarbene: A Versatile Synthon-Enabling Divergent Synthesis of Nitrogen Heterocycles

Over the past several years, rhodium-azavinylcarbene (Rh-AVC) has grown into an enabling synthon for the synthesis of diverse nitrogen heterocycles. Herein we present an overview of our recent achievements in this field, including the Rh-AVC-promoted formal [4+3], [3+3], and [3+2] cycloadditions. These reactions allow for the efficient synthesis of several classes of important nitrogen heterocycles, such as azepines, pyrroles, and pyrazines. Some relevant works from other groups are also briefly discussed. 1 Introduction 2 Formal [4+3] and [3+2] Cycloadditions of 1,2,3-Triazoles with 1,3-Dienes 3 Formal [3+2] Cycloadditions of 1,2,3-Triazoles with Silyl or Alkyl Enol Ethers 4 Formal [3+3] and [3+2] Cycloadditions of 1,2,3-Triazoles with 2<i>H</i>-Azirines 5 Conclusion and Perspective

Facile synthesis of pyrroles via Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers

A novel Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers has been developed, which enables the facile synthesis of substituted pyrroles in a regiocontrollable manner. Moreover, the methodology could be extended to access 3-pyrrolin-2-one derivatives with silyl ketene acetals used as the reaction partner.

ChemInform Abstract: Palladium‐Catalyzed Reactions of Enol Ethers: Access to Enals, Furans, and Dihydrofurans.

AbstractThe present oxidation reaction of alkyl enol ethers to enals employs low loadings of the palladium catalyst.

Palladium-Catalyzed Reactions of Enol Ethers: Access to Enals, Furans, and Dihydrofurans

The palladium-catalyzed oxidation of alkyl enol ethers to enals, which employs low loadings of a palladium catalyst, is described. The mild oxidation conditions tolerate a diverse array of functional groups, while allowing the formation of di-, tri-, and tetrasubtituted olefins. The application of this methodology to intramolecular reactions of alkyl enol ethers containing pendant alcohols provides furan and 2,5-dihydrofuran products.

Catalytic Asymmetric Addition of Alkyl Enol Ethers to 1,2-Dicarbonyls

In this paper, the first example of catalytic enantioselective hetero-ene reaction of alkyl enol ethers with 1,2-dicarbonyl compounds is reported. With the use of the chiral N,N′-dioxide complex of Mg(OTf)2 or Co(OTf)2 isatins, α-keto esters, and glyoxal derivatives were converted into the desired products with good to excellent yields (up to 98%) and excellent enantioselecti­vities (up to >99% ee). The protocol is notable for the broad substrate tolerance, experimental simplicity, and mild conditions. 3-Substituted 3-hydroxyindoles obtained from isatins are particularly important in light of their biological significance. The synthetic potential of the developed methodology was exemplified by preparation of (R)-convolutamydine with 97% ee. A plausible transition state was modeled based on the product stereochemistry, HRMS, and X-ray studies.

ChemInform Abstract: Enantioselective Aldol Chemistry via Alkyl Enol Ethers. Scope of the Lewis Acid Catalyzed Condensation of Optically Active Trimethylsilyl and Methyl 2-((E)-1-Alkenyloxy)ethanoates with Acetals.

Optically active, mono- and disubstituted trimethylsilyl 2-[(E)-1-alkenyloxy]ethanoates of the type RR 1 CH=CHOCHR 2 CO 2 SiMe 3 (R=Me, PhCH 2 , n-Bu, MeO 2 CCMe 2 CH 2 , PhSCH 2 ; R 1 =H, Me; R 2 =Me, c-C 6 H 11 ) undergo highly dioastereoselective, Lewis acid catalyzed reactions with aliphatic and aromatic acetals R 3 CH(OR 4 ) 2 (R 3 =H, Me, t-Bu, Ph; R 4 =Me, CH 2 Ph) to afford cis-2-[RR 1 CH(R 3 CHOR 4 )]-5-R 2 -1,3-dioxolanones corresponding to erythro-diastereoselective aldol reactions involving net syn-periplanar addition of the acetal-derived electrophile and trimethylsilyl ester oxygen across the enol ether double bond

ChemInform Abstract: [2 + 2] Cycloaddition Reaction of Alkyl Enol Ethers with Acrylates by in situ Generated Silyl Triflic Imide Catalyst.

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(2+2) Cycloaddition Reaction of Alkyl Enol Ethers with Acrylates by in Situ Generated Silyl Triflic Imide Catalyst

We describe here (2+2) cycloaddition reaction of alkyl enol ethers with acrylates catalyzed by triethylsilyl triflic imide (Et3SiNTf2), which was in situ generated from triethylsilane and triflic imide. The reaction efficiently provides substituted cyclobutanes bearing alkoxy function in a stereoselective manner.