A novel nucleophilic substitution of in situ generated 3-tert-butyldimethyl- silyloxyalk-2-enylsulfonium salts with allylindium reagents

[reaction: see text] In situ generated 3-tert-butyldimethylsilyloxyalk-2-enylsulfonium salts derived from the reaction of alpha,beta-enones with dimethyl sulfide in the presence of TBSOTf undergo a novel nucleophilic substitution with in situ generated allylindium reagents from indium and allyl halides to give silyl enol ethers of delta,epsilon-unsaturated ketones, which correspond to Michael addition products, in good yields.     

Zn-mediated rhodium-catalyzed α-trifluoromethylation of ketones via silyl enol ethers

The treatment of silyl enol ethers of ketones with CF₃-I and Et₂Zn in the presence of RhCl(PPh₃)₃ in DME gave α-trifluoromethyl ketones in good yields. The reaction can be widely applicable to silyl enol ethers derived from aliphatic or aromatic ketones. In the absence of the rhodium catalyst, the reaction was very slow and the yields were quite poor.     

A novel alpha-arylation of ketones,aldehydes, and esters via a photoinduced SN1 reaction through 4-aminophenyl cations

4-Aminophenyl cations (expediently generated by photolysis of 4-chloroaniline and its N,N-dimethyl derivative by photolysis in MeCN) added to enamines and gave the corresponding alpha-(4-aminophenyl) ketones in satisfactory yields. The yields of the same ketones were increased when silyl enol ethers were used in the place of enamines. The alpha-arylation of silyl enol ethers of aldehydes occurred with lower yields and only with the N,N-dimethyl derivative. The procedure was successful with ketene silyl acetals giving in a single step a good yield of alpha-(4-aminophenyl)propionic(acetic) esters, known intermediates for the preparation of analgesic compounds. The reaction of the aryl cation with Danishefsky's diene gave the arylated beta-methoxy enone. The method is complementary to the recently developed palladium-catalyzed alpha-arylation and occurs under neutral conditions.     

Radical trifluoromethylation of ketone silyl enol ethers by activation with dialkylzinc

[reaction: see text] The radical trifluoromethylation of ketone silyl enol ethers gave alpha-CF(3) ketones in good yields with wide scope of the ketonic substrates including acyclic ketones and cyclopentanone. The use of dialkylzinc to activate the silyl enol ethers is the key to the efficient radical trifluoromethylation.     

Oxidative conversion of silyl enol ethers to α,β-unsaturated ketones employing oxoammonium salts

The oxidative conversion of silyl enol ethers to α,β-unsaturated ketones using a less-hindered class of oxoammonium salts (AZADO(+)BF(4)(-)) is described. The reaction proceeds via the ene-like addition of oxoammonium salts to silyl enol ethers.     

Catalytic,asymmetric Mannich-type reactions of N-acylimino esters: reactivity,diastereo- and enantioselectivity,and application to synthesis of N-acylated amino acid derivatives

In the presence of a catalytic amount of Cu(OTf)(2)-chiral diamine 3e complex, N-acylimino esters reacted with silyl enol ethers to afford the corresponding Mannich-type adducts in high yields with high enantioselectivities. A wide variety of silyl enol ethers derived from ketones, as well as esters and thioesters, reacted smoothly. In the reactions of alpha-substituted silyl enol ethers (alpha-methyl or benzyloxy), the desired syn-adducts were obtained in high yields with high diastereo- and enantioselectivities. Several intermediates for the synthesis of biologically important compounds were prepared using this novel catalytic asymmetric Mannich-type reaction, and at the same time, absolute and relative stereochemical assignments were made. In addition, it has been revealed that alkyl vinyl ethers reacted with N-acylimino esters in the presence of a catalytic amount of the Cu(II) catalyst to give the corresponding Mannich-type adducts in high yields with high enantioselectivities. This is the first example of catalytic asymmetric Mannich-type reactions with alkyl vinyl ethers. The reaction mechanism, structure of chiral catalyst-electrophile complexes, and transition states of these catalytic asymmetric reactions were assumed based on X-ray crystallographic analysis of the Cu(II)-chiral amine complex, PM3 calculations, and FT-IR analyses, etc. Finally, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12, 1), a new inhibitor of ceramide trafficking from endoplasmic reticulum to the site of sphingomyerin (SM) synthesis, has been synthesized efficiently using the present Mannich-type reaction as a key step. The synthesis involved three steps (two-pot), and total yield was 82.9%.     

1,3-Addition of silyl enol ethers to nitrones catalyzed by mesoporous aluminosilicate

Mesoporous aluminosilicate (Al-MCM-41) was found to be an effective and reusable catalyst for 1,3-addition of silyl enol ethers to nitrones. The reaction proceeded under mild reaction conditions to afford the corresponding β-(siloxyamino)ketones in high yields. Furthermore, a unique chemoselectivity of a nitrone over an aldehyde and an acetal, which are more reactive toward silyl enol ether in the presence of Al-MCM-41 than a nitrone, was observed.     

Chiral Brønsted acid from a cationic gold(I) complex: catalytic enantioselective protonation of silyl enol ethers of ketones

A chiral Br?nsted acid has been developed from a cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to the enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities, including cyclic ketones bearing aliphatic substrates at the α-position. Furthermore, the application of this Br?nsted acid was extended to the first Br?nsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.     

Easy access to CF2-containing molecules based on the reaction of 2,2,3,3-tetrafluorooxetane with various nucleophiles

2,2,3,3-Tetrafluorooxetane reacted easily with organolithium reagents to give 1,1,3-trisubstituted 2,2-difluoropropan-1-ols in good to excellent yields. On the other hand, the reaction with Grignard reagent led to 3-bromo-1,1-disubstituted 2,2-difluoropropan-1-ols in good yields. On treating with lithium enolates, generated from enol silyl ethers and MeLi/LiBr, the corresponding 1-bromo-2,2-difluoro-3,5-dicarbonyl compounds were obtained in fair to good yields. 3-Iodo-2,2-difluoropropanoate, prepared readily from 2,2,3,3-tetrafluorooxetane and NaI, reacted successfully with various silyl enol ethers in the presence of a radical initiator to provide the corresponding coupling products in good yields.     

Mild electrophilic trifluoromethylation of beta-ketoesters and silyl enol ethers with 5-trifluoro methyldibenzothiophenium tetrafluoroborate

Cyclic and acyclic beta-ketoesters were efficiently trifluoromethylated with 5-trifluoromethyldibenzothiophenium tetrafluoroborate in the presence of a phase-transfer catalyst to afford the corresponding alpha-substituted alpha-trifluoromethyl beta-ketoesters in good to excellent yields. In a second approach, 5-trifluoromethyldibenzothiophenium tetrafluoroborate and tetrabutylammonium difluorotriphenylstannate were used for efficient electrophilic trifluoromethylation of various silyl enol ethers leading to the corresponding alpha-trifluoromethyl ketones in good to high yields.     

Synthesis of mono- and difluoroacetyltrialkylsilanes and the corresponding enol silyl ethers

A variety of mono- and difluoroacetylsilanes and the corresponding silyl enol ethers were prepared from trifluoroethanol and chlorotrialkylsilanes in the presence of LDA through retro-Brook rearrangement. Sterically demanding silyl groups, especially those bound to oxygen, resulted in higher yields of difluoroacetylsilanes. The yields of difluoroacetylsilanes were also dramatically affected by the method of the termination of the reaction. Difluorohaloacetylsilanes were prepared from the corresponding difluoroethenyl silyl ethers with electrophilic halogenating reagents in good yields. A gamma-fluorinated beta-diketone 9a was prepared from monofluoroacetyltriisopropylsilane by nucleophilic acylation with methyl trifluoroacetate.     

Copper‐Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol‐substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl‐protected enol, since the corresponding acetyldiazoimide failed to provide any cross‐products in metal‐catalyzed reactions with sulfur ylides. This copper‐catalyzed cycloaddition is initiated with the generation of enol‐substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six‐membered ring formation, C?O and C?S bond cleavage, and silyl and acetyl group migration.     

Preparation of silyl enol ethers using (bistrimethylsilyl)acetamide in ionic liquids

[reaction: see text]. Ionic liquids have been used for the preparation of silyl enol ethers from aldehydes and ketones with (bistrimethylsilyl)acetamide (BSA) in good yields.     

alpha-Nitration of Ketones via Enol Silyl Ethers. Radical Cations as Reactive Intermediates in Thermal and Photochemical Processes

Highly colored (red) solutions of various enol silyl ethers and tetranitromethane (TNM) are readily bleached to afford good yields of alpha-nitro ketones in the dark at room temperature or below. Spectral analysis show the red colors to be associated with the intermolecular 1:1 electron donor-acceptor (EDA) complexes between the enol silyl ether and TNM. The formation of similar vividly colored EDA complexes with other electron acceptors (such as chloranil, tetracyanobenzene, tetracyanoquinodimethane, etc.) readily establish enol silyl ethers to be excellent electron donors. The deliberate irradiation of the diagnostic (red) charge-transfer absorption bands of the EDA complexes of enol silyl ethers and TNM at -40 degrees C affords directly the same alpha-nitro ketones, under conditions in which the thermal reaction is too slow to compete. A common pathway is discussed in which the electron transfer from the enol silyl ether (ESE) to TNM results in the radical ion triad [ESE(*)(+), NO(2)(*), C(NO(2))(3)(-)]. A subsequent fast homolytic coupling of the cation radical of the enol silyl ether with NO(2)(*)() leads to the alpha-nitro ketones. The use of time-resolved spectroscopy and the disparate behavior of the isomeric enol silyl ethers of alpha- and beta-tetralones as well as of 2-methylcyclohexanone strongly support cation radicals (ESE(*)(+)) as the critical intermediate in thermal and photoinduced electron-transfer as described in Schemes 1 and 2, respectively.     

Lewis base catalyzed Mannich-type reactions between trimethylsilyl enol ethers and aldimines

Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and N-tosylaldimines is described. Nitrogen anions generated from amides or imides such as lithium benzamide or potassium phthalimide are found to be effective Lewis base catalysts in DMF at room temperature to afford the corresponding beta-amino carbonyl compounds in good to high yields; the oxygen anion generated from carboxylic acids such as lithium acetate was also found to be effective in dry DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene acetal proceeded smoothly even in water-containing DMF. Then, Lewis base catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide, and aromatic aldehyde having electron-withdrawing group such as p-nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford the corresponding beta-amino ester in good yield. Further, ammonium carboxylates such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to be more effective Lewis base catalysts in the above-mentioned Mannich-type reaction. The synthesis proceeded in various solvents at lower temperatures. The reaction between aldimines and TMS enol ethers generated from thioester and various ketones such as propiophenone or cyclohexanone also proceeded smoothly to afford the corresponding beta-amino carbonyl compounds in high yields with good to high anti-selectivities.     

Bismuth triflate-catalyzed three-component mannich-type reaction

Bismuth triflate catalyzes the Mannich-type reaction of a variety of in situ generated aldimines using aldehydes, anilines, and silyl enol ethers in a three-component reaction. The reaction proceeds rapidly and affords the corresponding protected beta-amino ketones in high yields (up to 94%).     

The mannich reaction-II : Derivatization of aldehydes and ketones using dimethyl(methylene)ammonium salts

Aldehydes and ketones have been converted efficiently to their corresponding Mannich products by various dimethyl(methylene)ammonium salts under a range of reaction conditions. The several methods used to form these derivatives are compared. Excellent approaches to aldehyde derivatives involve treating the enol silyl ether of the carbonyl compound with methyllithium and then an iminium salt, or directly adding the iminium salt to the enol silyl ether. Ketones may be derivatized effectively by treatment with potassium hydride, followed by an iminium salt, or from the enol silyl ether by addition of the iminium reagent. Use of iminium reagents in the Mannich reaction is recommended because the yields are often good and the site of attachment on an unsymmetrical ketone is both predictable and controllable.     

W(CO)5(L)-catalyzed endo-selective cyclization of allenyl silyl enol ethers: an efficient method for the cyclopentene annulation onto alpha,beta-unsaturated ketones

[reaction: see text] Indium-mediated allenylation of alpha,beta-unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfide gives 6-siloxy-1,2,5-trienes, which undergo W(CO)(5)(L)-catalyzed 5-endo cyclization to give the corresponding cyclopentene derivatives in good yield. Furthermore, this novel W(CO)(5)(L)-catalyzed cyclization of allenyl silyl enol ethers proceeds in a 6-endo manner when 5-siloxy-1,2,5-trienes are employed as a substrate. In these reactions, effective electrophilic activation of allenyl compounds for attack by silyl enol ethers is achieved using a catalytic amount of W(CO)(6).     

Et(3)B-Induced Hydrogermylation of Alkenes and Silyl Enol Ethers

Tri-2-furanylgermane in the presence of a catalytic amount of Et(3)B adds to internal alkenes as well as terminal alkenes effectively to give the corresponding adducts in good to excellent yields. The addition of tri-2-furanylgermane to silyl enol ethers followed by elimination of germyl and siloxy moieties provides a new route for the conversion of ketones into alkenes.     

Triethylborane-induced hydrogermylation of alkenes with tri-2-furylgermane

Tri-2-furylgermane in the presence of a catalytic amount of triethylborane adds to internal alkenes as well as to terminal alkenes effectively, giving the corresponding adducts in good to excellent yields. The addition of tri-2-furylgermane to silyl enol ethers followed by elimination of germyl and siloxy moieties provides a new route for the conversion of ketones into alkenes.