Catalytic asymmetric aldol reactions in aqueous media using chiral bis-pyridino-18-crown-6-rare earth metal triflate complexes

Catalytic asymmetric aldol reactions in aqueous media have been developed using Pr(OTf)(3) and chiral bis-pyridino-18-crown-6 1. In the asymmetric aldol reaction using rare earth metal triflates (RE(OTf)(3)) and 1, slight changes in the ionic diameters of the metal cations greatly affected the diastereo- and enantioselectivities of the products. The substituents (MeO, Br) at the 4-position of the pyridine rings of the crown ether did not significantly affect the selectivities in the asymmetric aldol reaction, although they affected the binding ability of the crown ether with RE cations and the catalytic activity of Pr(OTf)(3)-crown ether complexes. From X-ray structures of RE(NO(3))(3)-crown ether complexes, it was found that they had similar structures regardless of the RE cations and the crown ethers used. Accordingly, the binding ability of the crown ether with the RE cation and the catalytic activity of the complex are important for attaining high selectivity in the asymmetric aldol reaction. Various aromatic and alpha,beta-unsaturated aldehydes and silyl enol ethers derived from ketones and a thioester can be employed in the catalytic asymmetric aldol reactions using Pr(OTf)(3) and 1, to provide the aldol adducts in good to high yields and stereoselectivities. In the case using the silyl enol ether derived from the thioester, 2,6-di-tert-butylpyridine significantly improved the yields of the aldol adducts.     

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.     

Catalytic asymmetric hydrosilylation of ketones: I. Chiral phosphine-platinum(II) complex-catalyzed hydrosilylation.

Dichlorobis(dimethylphenylphosphine)di-μ-chlorodiplatinum(II) was found to be an effective catalyst for the hydrosilylation of alkyl phenyl ketones with methyldichlorosilane to give the corresponding silyl ethers of 1-phenylalkanols. In the case of dialkyl ketones, the reaction was accompanied by formation of silyl enol ethers in considerable amounts. Asymmetric hydrosilylation of a series of alkyl phenyl ketones catalyzed by chiral phosphine- platinum(II) complexes was undertaken. The products were readily converted into partially active 1-phenylalkanols.     

Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction of a dicobalt acetylene complex

An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl₂, 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triisopropylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity.     

Stereoselective synthesis of cycloheptanone derivatives via an intermolecular [5 + 2] cycloaddition reaction

[reaction: see text] A [5 + 2] cycloaddition reaction of a new five-carbon unit was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl(2), [5-benzoyloxy-2-(triisopropylsiloxy)-1-penten-3-yne)]dicobalt hexacarbonyl reacted with enol triisopropylsilyl ethers to yield seven-membered dicobalt acetylene complexes in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity. The cycloadducts can be easily converted into various kinds of cycloheptanone derivatives.     

Access to Vinyl Ethers and Ketones with Hypervalent Iodine Reagents as Oxy-Allyl Cation Synthetic Equivalents

We report an Umpolung strategy of enol ethers to generate oxy-allyl cation equivalents based on the use of hypervalent iodine reagents. Under mild basic conditions, the addition of nucleophiles to aryloxy-substituted vinylbenziodoxolone (VBX) reagents, easily available in two steps from silyl alkynes, resulted in the stereoselective formation of substituted aryl enol ethers. The reaction was most efficient with phenols as nucleophiles, but preliminary results were also achieved for C- and N- nucleophiles. In absence of external nucleophiles, the 2-iodobenzoate group of the reagent was transferred. The obtained aryl enol ethers could then be transformed into α-difunctionalized ketones by oxidation. The described “allyl cation”-like reactivity contrast with the well-established “vinyl-cation” behavior of alkenyl iodonium salts.     

Direct transformation of silyl enol ethers into functionalized allenes

The first elimination reactions of silyl enol ethers to lithiated allenes are reported. These reactions allow a direct transformation of readily available silyl enol ethers into functionalized allenes. The action of three to four equivalents of lithium diisopropylamide (LDA) on silyl enol ethers results in the formation of lithiated allenes by initial allylic lithiation, subsequent elimination of a lithium silanolate, and finally, lithiation of the allene thus formed. Starting with amide-derived silyl imino ethers, lithiated ketenimines are obtained. A variety of reactions of the lithiated allenes with electrophiles (chlorosilanes, trimethylchlorostannane, dimethyl sulfate and ethanol) were carried out. Elimination of silanolate is observed only for substrates that contain the hindered SiMe2tBu or Si(iPr)3 moiety, but not for the SiMe3 group. The reaction of 1,1-dilithio-3,3-diphenylallene with ketones provides a convenient access to novel 1,1-di(hydroxymethyl)allenes which undergo a domino Nazarov-Friedel-Crafts reaction upon treatment with p-toluenesulfonic acid.     

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.     

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.     

Access to Vinyl Ethers and Ketones with Hypervalent Iodine Reagents as Oxy‐Allyl Cation Synthetic Equivalents

We report an Umpolung strategy of enol ethers to generate oxy‐allyl cation equivalents based on the use of hypervalent iodine reagents. Under mild basic conditions, the addition of nucleophiles to aryloxy‐substituted vinylbenziodoxolone (VBX) reagents, easily available in two steps from silyl alkynes, resulted in the stereoselective formation of substituted aryl enol ethers. The reaction was most efficient with phenols as nucleophiles, but preliminary results were also achieved for C‐ and N‐ nucleophiles. In absence of external nucleophiles, the 2‐iodobenzoate group of the reagent was transferred. The obtained aryl enol ethers could then be transformed into α‐difunctionalized ketones by oxidation. The described “allyl cation”‐like reactivity contrast with the well‐established “vinyl‐cation” behavior of alkenyl iodonium salts.     

A novel aminomethylation of silyl enol ethers with aminomethyl ethers catalyzed by iodotrimethylsilane or trimethylsilyl trifluoromethanesulfonate

The iodotrimethylsilane-catalyzed reaction of silyl enol ethers with aminomethyl ethers in acetonitrile gives aminomethylation products of the corresponding ketones readily. The reaction can slso be catalyzed by trimethylsilyl trifluoromethanesulfonate in dichloromethane.     

Regiochemical aspects in the reaction of 2,3,5-tri-o-benzoyl-d-ribofuranosyl : Acetate with silyl enol ethers catalyzed by stannic chloride

In the reaction with silyl enol ethers catalyzed by stannic chloride, 2,3,5-tri-O-benzoyl-D-ribofuranosyl acetate behaves as an ambident electrophile; silyl enol ethers of ketones having α-hetero substituents afford C-1 adducts, whereas those of usual acyclic ketones give products arising from attack on C-2 benzoxyl group.     

Mechanistic studies of Ce(IV)-mediated oxidation of beta-dicarbonyls: solvent-dependent behavior of radical cation intermediates

The Ce(IV)-initiated oxidation of synthetically relevant beta-diketones and beta-keto silyl enol ethers was explored in three solvents: acetonitrile, methylene chloride, and methanol. The studies presented herein show that the rate of reaction between Ce(IV) and the substrates is dependent upon the polarity of the solvent. Thermochemical studies and analysis are interpreted to be consistent with transition state stabilization by solvent being primarily responsible for the rate of substrate oxidation. Kinetic investigation of radical cations obtained from oxidations of beta-diketones reveals that a more ordered transition state for the radical cation decay is achieved through the direct involvement of methanol in the deprotonation of the intermediate. In the case of radical cations derived from beta-keto silyl enol ethers, experimental data support a mechanism involving unimolecular decay of the intermediate. Remarkably, radical cations derived from beta-diketones and beta-keto silyl enol ethers are surprisingly stable in methylene chloride.     

Studies on the reactions of silyl enol ether with perfluoroorganic compounds I. The reaction of silyl enol ether with perfluoroalkyl iodide

The reaction of silyl enol ethers ( 1a-1e ) with perfluoroalkyl iodides ( 2f–2k ) initiated with sodium dithionite was studied. α-Perfluoroalkyl ketones (3) were synthesized in excellent yield by this method. α, β-Unsaturated fluorinated ketones (4) were obtained easily by dehydrofluorination of the α-perfluoroalkyl ketones. A radical mechanism was proposed.     

无金属条件下I2/TBHP体系促进磺酰肼与烯醇硅醚自由基偶联反应合成α-磺酰基酮

在以单质碘(I₂)为催化剂, 叔丁基过氧化氢(TBHP)为氧化剂条件下, 使烯醇硅醚与各种取代的磺酰肼发生自由基磺酰化反应, 经自由基加成和氧化反应, 再水解脱去三甲基碘硅烷(Me₃SiI), 在最优条件下, 以22%~72%的收率合成了22种具有不同取代基的α-磺酰基酮衍生物, 采用核磁共振波谱表征了终产物的结构. 实验结果表明, 该方法具有良好的底物普适性, 氟、 氯、 硝基、 三氟甲基、 呋喃和萘等取代基团均能顺利发生转化, 得到相应的目标产物.     

Quenching of metal‐catalyzed living radical polymerization with silyl enol ethers

Various silyl enol ethers were employed as quenchers for the living radical polymerization of methyl methacrylate with the R Cl/RuCl₂(PPh₃)₃/Al(Oi–Pr)₃ initiating system. The most effective quencher was a silyl enol ether with an electron‐donating phenyl group conjugated with its double bond [CH₂C(OSiMe₃)(4‐MeOPh) ( 2a )] that afforded a halogen‐free polymer with a ketone terminal at a high end functionality [F̄_n ∼ 1]. Such silyl compounds reacted with the growing radical generated from the dormant chloride terminal and the ruthenium complex to give the ketone terminal via the release of the silyl group along with the chlorine that originated from the dormant terminal. In contrast, less conjugated silyl enol ethers such as CH₂C(OSiMe₃)Me were less effective in quenching the polymerization. The reactivity of the silyl compounds to the poly(methyl methacrylate) radical can be explained by the reactivity of their double bonds, namely, the monomer reactivity ratios of their model vinyl monomers without the silyloxyl groups. The lifetime of the living polymer terminal was also estimated by the quenching reaction mediated with 2a . © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4735–4748, 2000     

Alkoxy radical cyclizations onto silyl enol ethers relative to alkene cyclization, hydrogen atom transfer, and fragmentation reactions

This study examines the chemoselectivity of alkoxy radical cyclizations onto silyl enol ethers compared to competing cyclizations, 1,5-hydrogen atom transfers (1,5-HATs), and β-fragmentations. Cyclization onto silyl enol ethers in a 5-exo mode is greatly preferred over cyclization onto a terminal alkene. The selectivity decreases when any alkyl substitution is present on the competing alkene radical acceptor. Alkoxy radical 5-exo cyclizations displayed excellent chemoselectivity over competing β-fragmentations. Alkoxy radical 5-exo cyclizations onto silyl enol ether also outcompeted 1,5-HATs, even for activated benzylic hydrogen atoms. In tetrahydropyran synthesis, where 1,5-HAT has plagued alkoxy radical cyclization methodologies, 6-exo cyclizations were the dominant mode of reactivity. β-Fragmentation still remains a challenge for tetrahydropyran synthesis when an aryl group is present in the β position.     

Chiral Zinc(II)‐Catalyzed Enantioselective Tandem α‐Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines

A new catalytic asymmetric tandem α‐alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N′‐dioxide/Zn^II complexes. The proton shift preferentially proceeded instead of a silyl shift after α‐alkenyl addition of silyl enol ether to the ketimine. A wide range of β‐amino silyl enol ethers were synthesized in high yields with good to excellent ee values. Control experiments suggest that the Mukaiyama–Mannich reaction and tandem α‐alkenyl addition/proton shift reaction are competitive reactions in the current catalytic system. The obtained β‐amino silyl enol ethers were easily transformed into β‐fluoroamines containing two vicinal tetrasubstituted carbon centers.     

Rhodium-catalyzed α-fluoroalkylation reaction of ketones using silyl enol ethers

The treatment of silyl enol ethers with fluoroalkyl halides (R_f-X) in the presence of RhCl(PPh₃)₃ gave α-fluoroalkylated ketones. It seems that a rhodium complex derived from the silyl enol ether and RhCl(PPh₃)₃ played an important role for the oxidative addition of fluoroalkyl halides and the reductive elimination of the product.     

Indium-mediated beta-allylation,beta-propargylation,and beta-allenylation onto alpha,beta-unsaturated ketones: reactions of in-situ-generated 3-tert-butyldimethylsilyloxyalk-2-enylsulfonium salts with in-situ-generated organoindium reagents

3-tert-Butyldimethylsilyloxyalk-2-enylsulfonium salts, generated in situ from the reaction of alpha,beta-enones with dimethyl sulfide in the presence of TBSOTf, underwent a novel nucleophilic substitution with allylindiums to give silyl enol ethers of delta,epsilon-alkenyl ketones in good yields, which correspond to formal Michael addition products. In a similar manner, 1,4-propargylation of propargylindiums onto the sulfonium salts produced the corresponding silyl enol ethers of delta,epsilon-alkynyl ketones in good yields. Organoindium reagents derived from gamma-substituted propargyl bromide and indium afforded the corresponding silyl enol ethers of beta-allenyl ketones in good yields. The reaction proceeds via an addition-substitution mechanism involving the formation of allylic sulfonium salts. The presence of the intermediate sulfonium salt was confirmed by observation of the low-temperature (1)H NMR spectra.