Enol Ether Moiety Research Articles

Asymmetric Catalysis with Ethylene. Synthesis of Functionalized Chiral Enolates.

Trialkylsilyl enol ethers are versatile intermediates often used as enolate surrogates for the synthesis of carbonyl compounds. Yet there are no reports of broadly applicable, catalytic methods for the synthesis of chiral silyl enol ethers carrying latent functionalities useful for synthetic operations beyond the many possible reactions of the silyl enol ether moiety itself. Here we report a general procedure for highly catalytic (substrate:catalyst ratio up to 1000:1) and enantioselective (92% to 98% major enantiomer) synthesis of such compounds bearing a vinyl group at a chiral carbon at the β-position. The reactions, run under ambient conditions, use trialkylsiloxy-1,3-dienes and ethylene (1 atm) as precursors and readily available (bis-phosphine)-cobalt(II) complexes as catalysts. The silyl enolates can be readily converted into novel enantiopure vinyl triflates, a class of highly versatile cross-coupling reagents, enabling the syntheses of other enantiomerically pure, stereodefined trisubstituted alkene intermediates not easily accessible by current methods. Examples of Kumada, Stille, and Suzuki coupling reactions are illustrated.

ChemInform Abstract: Cycloisomerization of Allene—Enol Ethers under Bi(OTf)3 Catalysis.

AbstractBi(OTf)3 selectively promotes the activation of the enol ether moiety of the substrate accessing interesting functionalized cyclopentene rings.

ChemInform Abstract: Facile Synthesis of Multifunctionalized Allenes by Magnesium‐Promoted Reductive Silylation of Aromatic Conjugated Ynones.

AbstractMultifunctionalized allenes with a vinyl silane and a silyl enol ether moiety are prepared from alkyl/arylalkynyl ketones using different monochlorotrialkylsilanes.

Structural Requirements of Strigolactones for Shoot Branching Inhibition in Rice and Arabidopsis.

The structural requirements of strigolactones (SLs) involved in germination induction of root parasitic plants and hyphal branching in arbuscular mycorrhizal (AM) fungi have been extensively studied. However, our knowledge of the requirements of SLs involved in shoot branching inhibition in plants is still limited. To address this question, we investigated the structure-activity relationships of SLs in shoot branching inhibition in rice and Arabidopsis. SLs possess a four-ring structure, with a tricyclic lactone (ABC-rings) connected to a methylbutenolide part (D-ring) via an enol ether bridge. Here, we show that the the (R) configuration at C-2', which determines the steric position of the D-ring relative to the enol ether olefin bond, is critical for the hormonal activity in rice. Replacement of the enol ether moiety by an alkoxy or imino ether resulted in a severe reduction in biological activity in rice. Moreover, yeast two-hybrid experiments using a possible SL receptor, DWARF14 (D14), and a repressor in the SL signaling pathway, DWARF53 (D53), showed that D14 can interact with D53 in the presence of (2'R) stereoisomers of SLs, but not (2'S) stereoisomers, suggesting that the stereostructure of SLs is crucial for the interaction of these proteins. When GR5, an AB-ring-truncated analog, was applied to the hydroponic culture medium, strong inhibition of shoot branching was observed both in rice and in Arabidopsis. However, GR5 was only weakly active when directly applied to the axillary buds of Arabidopsis. Our results indicate that the difference in plant species and application methods greatly influences the apparent SL biological activity.

Cycloisomerization of allene-enol ethers under Bi(OTf)3 catalysis.

The cycloisomerization of allene-enol ethers under Bi(OTf)3 catalysis was developed as a novel "atom-economic" tool for accessing interesting functionalized cyclopentene rings. Bi(OTf)3 was shown to promote selectively the activation of the enol ether moiety of the substrate. This catalytic methodology was further extended to the synthesis of dihydrofuran and oxaspirocycle derivatives.

Facile synthesis of multifunctionalized allenes by magnesium-promoted reductive silylation of aromatic conjugated ynones

Mg-promoted reductive silylation of 4-phenyl-3-butyn-2-one in N,N-dimethylformamide (DMF) in the presence of chlorotrimethylsilane brought about double silylation at the β-carbon and oxygen atoms of the carbonyl group to give a multifunctionalized allene with a vinylsilane moiety and a silyl enol ether moiety. A variety of allenes can be synthesized through this simple methodology. Acid-catalyzed hydrolysis of an allene derived from the trimethylsilylation of 4-phenyl-3-butyn-2-one resulted in the formation of the corresponding benzalacetone with a trimethylsilyl group at the β-position of the carbonyl group in high yield.

ChemInform Abstract: Acid‐Mediated Cyclizations of SEM‐Protected Heterocyclic Anilines and Adjacent Hydroxyls of Enol‐Ethers.

AbstractSubstrates (I) undergo unexpected acid mediated cyclization involving the Sem‐protecting amino group and a neighboring enol ether moiety to produce tricyclic heterocycles (II).

Total Synthesis of Nucleoside Antibiotic A201A

A201A, a unique nucleoside antibiotic with potent antibacterial activities, has been synthesized for the first time in a total of 47 steps in a highly modular and linear manner, highlighting the elaboration/incorporation of an unprecedented hexofuranoside unit bearing an exocyclic enol ether moiety.

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C3-building block.

Herein we present the synthesis of the anhydrophytosphingosine jaspine B and three of its stereoisomers using a carbohydrate-derived alkoxyallene in order to obtain the products in enantiopure form. Key step of the reaction sequence is the addition of the lithiated alkoxyallene to pentadecanal, setting the configuration at the later C-2 of the ring system. This reaction step proceeds with moderate selectivity and therefore leads to a stereodivergent approach to the natural product and its enantiomer. The gold-catalyzed 5-endo-cyclization affords the corresponding dihydrofurans, which after separation, azidation of the enol ether moiety and two subsequent reduction steps give the natural product and its stereoisomers.

Toward the total synthesis of Luminamicin: construction of 14-membered lactone framework possessing versatile enol ether moiety

Luminamicin (1) was found to exhibit selective antibacterial activity against anaerobic bacteria by our group in 1985. The concise structure of 14-membered lactone of 1 was synthesized. Construction of a versatile enol ether moiety was achieved by Stille cross coupling via hydrostanylation of the ethynyl ether, and a maleic anhydride moiety was derived from the furan constitution by the oxidation after the macrolactonization at a late-stage.

Furanylidene systems from a tosylic acid-mediated, tandem desilylation-cyclization reaction of silyl ethers of monoalkynylated β-keto carbonyls

Abstract Single isomers of the furanylidene system 8 were synthesized in four steps. The synthesis begins with the dianion of β-keto carbonyls and culminates in a mild, tandem desilylation-cyclization reaction using tosylic acid. Compounds synthesized in this study have the potential for further diversification at the alkyne, carbonyl and enol-ether moieties. Hence, the furanylidenes from this study are prospective building blocks for biologically active, furan-containing natural products and their analogs.

Intramolecular regioselective addition of radicals and carbanions to ynol ethers. A strategy for the synthesis of exocyclic enol ethers

The scope and limitations of radical and anionic cyclization reactions involving halo ynol ethers have been investigated. 5- exo and 6- exo radical cyclizations of 6-iodo and 7-iodo ynol ethers proceeded well when the oxygen of the ynol ether was bearing an ethyl group. Exocyclic iodoenol ethers resulting from these cyclizations were highly unstable and decomposed rapidly. Li–I exchange of iodo ynol ethers proceeded smoothly at −78 °C. 6-Alkoxy-5-hexynyllithiums underwent regiospecific 5- exo-dig anionic cyclization to produce five-membered rings bearing an exocyclic enol ether moiety. The cyclized vinyllithium intermediate was successfully trapped with electrophiles to afford functionalized cycloalkoxyalkylidene derivatives in modest to good yields. 7-Alkoxy-6-heptynyllithiums did not cyclize via a 6- exo anionic process.

ChemInform Abstract: Rhenium(I)‐Catalyzed Cyclization of Silyl Enol Ethers Containing a Propargyl Carboxylate Moiety: Versatile Access to Highly Substituted Phenols.

AbstractDepending on the structure of the silyl enol ether moiety, either nucleophilic addition of the silyl enol ether moiety, or 1,2‐acyloxy migration occurs to give two kinds of substituted phenols.

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]‐Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3-siloxy-1,3,9-triene-7-yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)(5)(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl-substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven-membered rings were present. The reaction of (Z)-enol silyl ethers proceeded through Cope rearrangement of cis-divinylcyclopropane intermediates, and that of (E)-enol silyl ethers by 1,4-addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans - an approach to carbohydrate mimetics.

A stereodivergent synthesis of enantiopure 3,6-dihydro-2H-pyrans is presented. The addition of lithiated enol ethers to carbohydrate-derived nitrones afforded syn- or anti-configured hydroxylamine derivatives 4a–d that were cyclized under Lewis acidic conditions to yield functionalized dihydropyrans cis- or trans-5a–d containing an enol ether moiety. This functional group was employed for a variety of subsequent reactions such as dihydroxylation or bromination. Bicyclic enol ether 19 was oxidatively cleaved to provide the highly functionalized ten-membered ring lactone 20. The synthesized enantiopure aminopyrans 24, 26, 28 and 30 can be regarded as carbohydrate mimetics. Trimeric versions of 24 and 28 were constructed via their attachment to a tricarboxylic acid core.

C2‐Functionalization of 1‐Substituted Imidazoles with Aldehydes and Electron‐Deficient Acetylenes: A Novel Three‐Component Reaction

AbstractA novel three‐component reaction between 1‐substituted imidazoles, aldehydes, and electron‐deficient acetylenes proceeds under mild conditions (20–25 °C, no catalyst, no solvent) to form an unknown family of C2‐functionalized imidazoles in up to 74 % yield, the function constituting a push–pull combination of enol ether and acrylic moieties. In the case of cyanophenylacetylene, the function is built up stereospecifically to have the (Z) configuration. The interaction presumably occurs via zwitterion and carbene intermediates. The results contribute to basic imidazole and acetylene chemistry and open a shortcut to promising drug candidates.

Indium Trichloride Mediated Cleavage of Acetonides in the Presence of Acid-Labile Functional Groups - Enhancing the Synthetic Utility of 1,3-Dioxolanyl-Substituted 1,2-Oxazines

Indium trichloride in an acetonitrile-water mixture chemoselectively cleaved the isopropylidene acetals of various 1,3-dioxolanyl-substituted 1,2-oxazines as well as carbohydrate derivatives. Deprotection of acetonides can be achieved in substrates susceptible for acid-induced cyclizations. Most importantly, enol ether moieties are not attacked and the presence of glycosidic linkages or acid-sensitive protecting groups such as tert-butyldimethylsilyl, 2-(trimethylsilyl)ethyl, or tert-butoxycarbonyl is also tolerated.

Stereoselective Synthesis of Medium-sized Cyclic Compounds through the Intramolecular Michael-type Reaction Utilizing Alkyne–Hexacarbonyldicobalt Complex Formation

Abstract Alkyne–hexacarbonyldicobalt complexes having silyl enol ether and electron-deficient alkene moieties on opposite ends were treated with MeAlCl2 in the presence of 2,6-di-t-butylpyridine in CH2Cl2 to give synthetically useful medium-sized cyclic products as a single stereoisomer in good yield.

Enantioselective Synthesis of Cyclic Enol Ethers and All-Carbon Quaternary Stereogenic Centers Through Catalytic Asymmetric Ring-Closing Metathesis

The first examples of catalytic asymmetric ring-closing metathesis (ARCM) reactions of enol ethers are reported. To identify the most effective catalysts, various chiral Mo- and Ru-based catalysts were screened. Although chiral Ru catalysts (those that do not bear a phosphine ligand) promote ARCM in some cases, such transformations proceed in <10% ee. In contrast, Mo-based alkylidenes give rise to efficient ARCM and deliver the desired products in the optically enriched form. Thus, Mo-catalyzed enantioselective transformations allow access to various five- and six-membered cyclic enol ethers in up to 94% ee from readily available achiral starting materials. The first examples of catalytic ARCM that lead to the formation of all-carbon quaternary stereogenic centers are also disclosed. Mechanistic models that offer a plausible rationale for the identity of major enantiomers as well as the observed levels of enantioselectivity are provided. Representative examples demonstrate that the enol ether moiety and the unreacted alkene of the ARCM products can be discriminated with excellent site selectivity (>98%).

Synthesis, Reactivity and Stereochemistry of New Phosphorus Heterocycles with 5‐ or 6‐Membered Rings

AbstractFor Abstract see ChemInform Abstract in Full Text.