Ytterbium reaction with ketones

Organoytterbium chemistry has been developed in the last 20 years, although the development rate is much slower than the other lanthanides like samarium or cerium. Dianionic complexes that are produced from the reaction of ytterbium with diaryl ketones react with various kinds of electrophiles including carbon-heteroatom unsaturated bonds.35 Phenylytterbium iodide, a Grignard-type reagent, is known to have reactivity toward carbon dioxide,36 aldehydes, ketones,37,37 and carboxylic acid derivatives38,3811 to form the corresponding adducts respectively. 

The earliest studies on this reaction began with an attempt to generate simple symmetrical pinacols. Reaction of 1 equiv. of ytterbium metal with 2 equiv. of a diaryl ketone in IllF/HMPA provided excellent yields of the corresponding symmetrical pinacols (equation 98). Interestingly, when equimolar quantities of ytterbium metal and benzophenone were employed, the sole product isolated after aqueous work-up was benzhydrol. When D2O was utilized to quench this reaction mixture, C-deuterated benzhy-drol was formed (equation 99). These latter results in cated that a discrete ketone dianionic intermediate was generated in the reaction between ytterbium metal and diaryl ketones. 

A solution of CjHjYb, prepared by the reaction of ytterbium metal and C Hjl in tetrahydrofuran reacts with ketones, aldehydes, and nitriles just as Grignard reagents would. However, with esters the complex reacts to produce ketones as the main product (Fukagawa et al., 1981). With benzoyl chloride the ketone is obtained selectively in modest yields which is in contrast to the Grignard reaction (Fukagawa et al., 1982). 

This triene was prepared via the silylation of ketone 166, and submitted without purification to a DA reaction with bis-activated dienophile 168. The transmitted diene generated from this reaction migrates upon addition of ytterbium(III) trifluoromethanesulfonate, yielding cross-conjugated enone 170. Upon heating in o-dichlorobenzene, an intramolecular DA reaction occurred, generating tricycle 171. Five steps were then required to access the amphilectene 172. 

As anticipated from the complexation experiments, reaction of 4.42 with cyclopentadiene in the presence of copper(II)nitrate or ytterbium triflate was extremely slow and comparable to the rate of the reaction in the absence of Lewis-acid catalyst. Apparently, Lewis-acid catalysis of Diels-Alder reactions of p-amino ketone dienophiles is not practicable. 

In 2001, the preparation of allylytterbium bromide and the synthesis of homoallylic alcohols using allylytterbium bromide were reported.39 393 Ytterbium metal was found to be activated by a catalytic amount of Mel at 0 °C in THF to produce allylytterbium bromide 66 (Equation (11)). The allylation reaction of a wide range of aromatic aldehydes and ketones proceeded at ambient temperature or less in good to high yields (Table 2). Imines also reacted with allylytterbium bromide to afford homoallyl amines (Table 3). 

For further contributions on the dia-stereoselectivity in electropinacolizations, see Ref. [286-295]. Reduction in DMF at a Fig cathode can lead to improved yield and selectivity upon addition of catalytic amounts of tetraalkylammonium salts to the electrolyte. On the basis of preparative scale electrolyses and cyclic voltammetry for that behavior, a mechanism is proposed that involves an initial reduction of the tetraalkylammonium cation with the participation of the electrode material to form a catalyst that favors le reduction routes [296, 297]. Stoichiometric amounts of ytterbium(II), generated by reduction of Yb(III), support the stereospecific coupling of 1,3-dibenzoylpropane to cis-cyclopentane-l,2-diol. However, Yb(III) remains bounded to the pinacol and cannot be released to act as a catalyst. This leads to a loss of stereoselectivity in the course of the reaction [298]. Also, with the addition of a Ce( IV)-complex the stereochemical course of the reduction can be altered [299]. In a weakly acidic solution, the meso/rac ratio in the EHD (electrohy-drodimerization) of acetophenone could be influenced by ultrasonication [300]. Besides phenyl ketone compounds, examples with other aromatic groups have also been published [294, 295, 301, 302]. 

Benzotriazole-based methodologies continued to be dominant in 2002. Reaction of diaryl ketones with aminoalkylbenzotriazoles in the presence of ytterbium metal at room temperature gave 2-amino alcohols in good yields under mild and neutral conditions <02TL2251>. 

The reduction of a carbon-carbon multiple bond by the use of a dissolving metal was first accomplished by Campbell and Eby in 1941. The reduction of disubstituted alkynes to c/ s-alkenes by catalytic hydrogenation, for example by the use of Raney nickel, provided an excellent method for the preparation of isomerically pure c -alkenes. At the time, however, there were no practical synthetic methods for the preparation of pure trani-alkenes. All of the previously existing procedures for the formation of an alkene resulted in the formation of mixtures of the cis- and trans-alkenes, which were extremely difficult to separate with the techniques existing at that time (basically fractional distillation) into the pure components. Campbell and Eby discovered that dialkylacetylenes could be reduced to pure frani-alkenes with sodium in liquid ammonia in good yields and in remarkable states of isomeric purity. Since that time several metal/solvent systems have been found useful for the reduction of C=C and C C bonds in alkenes and alkynes, including lithium/alkylamine, ° calcium/alkylamine, so-dium/HMPA in the absence or presence of a proton donor,activated zinc in the presence of a proton donor (an alcohol), and ytterbium in liquid ammonia. Although most of these reductions involve the reduction of an alkyne to an alkene, several very synthetically useful reactions involve the reduction of a,3-unsaturated ketones to saturated ketones. ... 

Indeed, it has been found that unsymmetrical pinacols can be generated in surprisingly high yields by treating 1 equiv. of a diaryl ketone with 1 equiv. of ytterbium metal, and subsequently quenching the resultant reaction mixture with a variety of aldehydes and ketones (equation 100). Yields in most cases are high, and this particular transformation represents one of the very few ways in which such a process can be accomplished efficiently. Reaction of benzophenone/ytterbium with 2-cyclohexen-l-one provides mixtures of 1,2- and 1,4-addition products, together with some benzhydrol. 

Taking into account the competitive hydrolysis of the silyl enol ether, this reaction is remarkable. The method was shown to be general and was extended to a variety of aldehydes and several a,j9-unsaturated carbonyl compounds giving uniformly 1,4-addition with aldehydes and a mixture of 1,4- and 1,2-adducts in the case of ketones [187]. Later, this aqueous version of the Mukaiya-ma reaction was shown to give near quantitative yields in the presence of a water-tolerant Lewis acid such as ytterbium triflate [188]. Keeping with the same concept,copper(II) triflate [189],indium(III) trichloride [190],tris(pentafluoro-phenyl)boron [191] and scandium(III) triflate in the presence of a surfactant [192] have proved to be active catalysts. 

The reaction of yne-ones (also synthons for 1,3-dicarbonyl compounds) with 3-amino-enones or 3-amino-acrylates (the Bohlmann-Rahtz reaction) is regioselective, since conjugate addition of the ketone enamine is the first step the intermediates thus produced can be isolated from reactions in ethanol and converted on to the aromatic pyridine Acetic acid or ytterbium triflate give good results. 

Considerable rate enhancements have been observed when water is used as solvent compared with alcoholic or hydrocarbon media for Mannich reactions, i.e. condensations of ketones with secondary amines in the presence of formaldehyde [65]. Allylsilanes [66] and allylstannanes [67] in aqueous media were used in organic synthesis under Mannich-like conditions. More recently, Kobayashi reported the catalysis of the reaction of vinyl ethers with iminium salts by ytterbium triflate in tetrahydrofuran-water mixtures [68]. 

Similar to diaryl ketones, aromatic thioketones and imines can also be reduced to the corresponding dianionic species. Fujiwara and coworkers have reported that the ytterbium diaryl thioketone dianion species, generated by reaction of Yb metal with the thioketones in THF/HMPA at low temperature, show good nucle-ophilicity towards organic substrates such as acetone and alkyl halides (Scheme 22) [31]. The thioketone dianion species seemed to be less stable than those of ketones. At room or higher temperatures, C-S bond cleavage reaction took place. 

Ytterbium triflate in an ionic liquid is an efficient catalyst for reaction of aldehydes and ketones with mercaptoethanol to form 2-substituted 1,3-oxathiolanes <04SL2785> and K-10 montmorillonite has been used for the same reaction where it shows selectivity for aldehydes over ketones <04SL1592>. The compound 76 has been used to introduce a mercapto acid unit into peptide analogues <04S1088> and the diastereoselectivity of addition of the anion of 77 to carbonyl compounds has been examined <03JHC979>. 

The use of Montmorillonite clay, a very efllcient acidic catalyst, allows a-alkylation of / -substituted indoles ytterbium triflate can also be used to catalyse such alkylations. This efficient catalysis contrasts with the different, but very instructive, reaction pathway followed when mesityl oxide and 1,3-dimethylindole are combined in the presence of sulfuric acid - electrophilic attack at the already substituted /3-position is followed by intramolecular nucleophilic addition of the enol of the side-chain ketone to C-2. ... 

Mlynarski et al. [16] developed ytterbium-catalyzed enantio- and diastereoselective aldol-Tishchenko reactions of symmetrical dialkyl ketones as enol components for the first time. As chiral ytterbium ligand, they employed the amino alcohol 32, which gave rise to aldol-Tishchenko products such as 33 with up to 86% ee (Scheme 8.10). As documented by control experiments and very similar to the above discussed processes, the rate- and stereo-determining step in this reaction was proven to be the Tishchenko reduction with a rapid pre-retro-aldol equilibrium of the initially formed aldol products. This process may be utilized for reactions of alkyl aryl ketones as well, broadening its scope significantly. 

A combination of ytterbium (or zinc) triflate and chiral C2-symmetric prolinamide ligand leads to high enantioselectivities in direct aldol reactions under aqueous conditions (Scheme 27). The presence of 5 mol% of the catalyst affords an asymmetric intermolecular aldol reaction between umnodified ketones and aldehydes to give antiproducts with excellent enantioselectivities up to 99% ee. 

Ytterbium triiodide activates the C-F bond of alkyl fluorides giving iodides in high yields (82-98%) in CH2CI2 or CHCls. The reaction is successful in the presence of ketone, ether, alcohol, ester, trialkylamine, aryl, and cyano groups in the substrate and with primary, secondary, and tertiary fluorides but does not occur with polyfluorinated compounds, or those with a CF2, CF3, or group. The reaction... 

More recently, it was shown that ytterbium metal reacts with alkyl or aryl iodides to give solutions of L-Yb-I species that react smoothly with ketones (Fukagawa et al., 1981). Similar reactions could be carried out with europium and samarium, which also have well-defined divalent forms (Asprey and Cunningham, 1960 Marks, 1978). 

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