Aldol lanthanide catalyzed

A tin(II)-catalyzed asymmetric aldol reaction and lanthanide-catalyzed aqueous three-component reaction have been used as the key steps for the synthesis of febrifugine and isofebrifugine (Scheme 8.31).293... 

One of the most important goals in organic chemistry is the formation of C-C bonds. This field has advanced rapidly due to the introduction of transition metal catalysts. Engberts and co-workers [18] observed an extraordinary rate enhancement (up to 1.8 10 fold) in the Diels-Alder reaction between 3-(/7ara-substituted phenyl)-l-(2-pyridyl)-2-propen-l-ones and cyclopentadiene in presence of cop-per(II) or zinc(II) dodecylsulfate micelles. The lanthanide-catalyzed aldol reaction described by Kobayashi and Manabe [19] is also important as a typical method in... 

Kobayashi et aL fulfilled first asymmetric synthesis of febrifugine utilizing tin(II)-catalyzed asymmetric aldol-type reaction and lanthanide-catalyzed... 

Achiral Lanthanide Lewis Acid Catalysis 637 Table 13.1 Aldol reaction catalyzed by lanthanide triflate in aqueous media... 

Polar polyoxyethylene-polyoxypropylene (POEPOP) resin, deriva-tized with a 4-hydroxymethyl phenoxy linker, was used as a solid support for lanthanide triflate-catalyzed Mukaiyama-type solid-phase aldol reactions.282 The use of an aqueous solvent was found to be crucial. The reactions on an N-terminal peptide aldehyde substrate proceeded in very high yields. 

The aldolization, a major synthetic tool involving a nucleophilic addition to the carbonyl double bond, is usually conducted under either acidic or basic conditions (Denmark and Lee, 1992). The yields of the aqueous aldolization logically follow the electrophilicity of the aldehyde, rising up to 82% using p-nitrobenzaldehyde. It has been shown that these aqueous aldolizations can be catalyzed by water-stable Lewis acids such as ytterbium or other lanthanide inflates (Kobayashi and Hachiya, 1992). 

A recent notable finding in this field is Mukaiyama aldol reactions in aqueous medium (THF H20 = 9 1) catalyzed by metal salts. Lewis acids based on Fe(II), Cu(II), and Zn(II), and those of some main group metals and lanthanides are stable in water. Remarkably, the aldol reaction shown in Sch. 29 occurs more rapidly than the hydrolysis of the silyl enol ether [137]. In the presence of surfactants (dodecyl sulfates or dodecane sulfonate salts), reactions of thioketene silyl acetals with benzaldehyde can be performed in water [138]. 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

Lanthanide triflate-catalyzed aldol reactions in water-containing solvents... 

Lanthanide(lII) chlorides or some organolanthanide compounds catalyzed aldol reactions of ketene silyl acetals with aldehydes were reported, (a) Takai, K. Heathcock, C. H. J. Org. Chem. 1985, 50, 3247. (b) Vougioukas, A.E. Kagan, H.B. Tetrahedron Lett. 1987, 28, 5513. (c) Gong,... 

Transition metal catalysis of the Michael reaction of 1,3-dicarbonyl compounds with acceptor activated alkenes has been known since the early 1980 s 2>3 It is a valuable alternative to the classic base catalysis of the reaction. Because of the mild and neutral conditions, the chemoselectivity of these reactions is superior to that provided by base catalysis, since the latter suffers from various unwanted side or subsequent reactions, such as aldol cyclizations, ester solvolyses or retro-Claisen type decompositions. A number of transition metal and lanthanide compounds have been reported to catalyze the Michael reaction, but FeCb 6 H20 is one of the most efficient systems to date. A number of 3-diketones or p-oxo esters and MVK are cleanly converted to the corresponding Michael reaction products within a few hours at room... 

Kobayashi et al. discovered that Yb(OTf)3 and other lanthanide triflates (l,ri(() lf)(, Ln=La, Pr, Nd, Sm, Eu, Gd, Dy, Ho, and Er) are excellent catalysts of hydroxymefhylation of propiophenone TMS enolate with aqueous formaldehyde solution at room temperature (Scheme 10.22) [70, 71]. The Yb(OTf) j-catalyzed hydroxymefhylation of a variety of SEE, including sterically hindered compounds, proceeds regiospecifically in high yield. In addition, almost 100% of Yb(OHf). is quite easily recovered from fhe aqueous layer and can be reused. Yb(OTf)3 also has high catalytic activity in fhe aqueous aldol reaction of other aldehydes. Interestingly, the catalytic activity is rather low in the absence of water. In aqueous media water would coordinate to ytterbium to form active ytterbium cations. 

Lanthanide triflates and Sc(OTf)3 effectively catalyze conjugate addition of SEE, KSA, and ketene silyl thioacetals under mild conditions (0°C to room temperature, 1-10 mol% catalyst) (Scheme 10.86) [69, 238]. After an aqueous work-up these Lewis acids can be recovered almost quantitatively from the aqueous layer and can be re-used without reduction of fheir catalytic activity. Eu(fod)3 also is effective in not only aldol reactions but also Michael addition of KSA [239]. The Eu(fod)3-catalyzed addition of KSA is highly chemoselective for enones in the presence of ketones. 

Lewis acid catalyzed aldol reaction or aldol-type reaction in general provides better yields. Early work on the aldol reaction in H2O medium focused primarily on lanthanide triflates (Scheme 5.4) as catalyst. ... 

The Lewis acidity of lanthanide complexes has been known for a long time. It was exploited extensively in their use as NMR shift reagents, mainly Eu(fod)3. They show strong affinity toward carbonyl oxygens and, therefore, have been widely used as catalysts for cycloaddition of dienes with aldehydes [25]. Moreover, the ability of catalytic amounts of lanthanide compoimds to activate coordinating nitriles as well as imines has also been recognized [26]. In recent years lanthanide (III) complexes have demonstrated clear effectiveness in catalyzing not only hetero-Diels-Alder reactions, but also Michael, aldol, Strecker and Friedel-Crafts acylation reactions [27]. 

Lanthanide triflates were found to be excellent Lewis acid catalysts not only in aqueous media but also in organic solvents. The reaction of ketene silyl acetal 3 with benzaldehyde proceeded smoothly in the presence of 10mol% Yb(OTf)3 in dichloromethane at -78°C, to afford the corresponding aldol-type adduct in 94% yield. The same reaction at room temperature also went quite cleanly without side reactions and the desired adduct was obtained in 95% yield. No adduct was obtained in THF-water or toluene-ethanol-water, because hydrolysis of the ketene silyl acetal preceded the desired aldol reaction in such solvents. In other organic solvents such as toluene, THF, acetonitrile, and DMF, Yb(OTf)3 worked well, and it was found that other Ln(OTf)3 also catalyzed the above aldol reaction effectively (85-95% yields). 

Although lanthanide triflates are the first metal salts which were foimd to catalyze aldol reactions of aldehydes with silyl enol ethers efficiently in aqueous media, it has been difficult to realize asymmetric versions of lanthanide triflate-catalyzed reactions in such media. Recently, the first example of this type of reaction using chiral bis-pyridino-18-crown-6 (1) has been developed [38]. In the reaction of benzaldehyde with silyl enol ethers in water-ethanol (1 9), the cation size of lanthanide triflates strongly affected the diastereo- and enantioselectivities of the aldol adduct. For the larger cations such as La, Ce, Pr, and Nd, both diastereo- and enantioselectivities were high, while the smaller cations such as Sc and Yb showed no enantioselection. 

Asymmetric hetero-Diels-Alder reactions of glyoxylate esters and Danishefsky s diene catalyzed by various chiral bis(oxazoline)-lanthanide complexes afforded the corresponding aldol adducts, which upon treatment with... 

A chiral lanthanide complex catalyzes asymmetric Mukaiyama aldol reactions in aqueous media (Scheme 24). The changes in the water-coordination number is key to the mechanism of die catalytic reaction. The precatalysts yielded -hydroxy carbonyl compounds from aliphatic and aryl substrates widi high diastereomeric ratios and enantiomeric excesses of up to 49 1 and 97%, respectively. 

Lewis acid catalysis is one of the most useful methods in modern organic synthesis. However, many of the common Lewis acids are highly water-labile and have been used in organic synthesis under strictly anhydrous conditions. Contrary to this, it was found that lanthanide triflates catalyzed aldol reactions of formaldehyde (Scheme 3.6). Formaldehyde is one of the most highly reactive Cl electrophiles. In this reaction, not gaseous formaldehyde but a commercially available aqueous solution was used as the formaldehyde source. This invaluable find introduced the concept of Lewis acid catalysis in aqueous media to many chemists. Later, it was also reported that other aldol reactions, with a variety of aldehydes and silyl enol ethers, as well as allylation reactions, proceeded smoothly in aqueous media to afford the desired compounds in high yields. ... 

Aldol Reactions Addition to Aldehydes and Imines. Since its discovery, the Mukaiyama aldol reaction. has attracted considerable attention and several improvements in reaction conditions have heen reported. Most useful catalysts for this reaction appear to he recently reported lanthanide triflates (eq 5), bis(cyclopentadienyl)titanium bis(trifluoromethanesulfonate), or Cp2Zr(OTf)2 THF. The metallocene salt also catalyzes additions to ketones (eq 6). This reaction can also be carried out under essentially neutral conditions by warming (70 °C) a stoichiometric mixture of the aldehyde and the KSA in acetonitrile (eq 7). When an optically active aldehyde is used, a slightly better stereochemical control is noticed under catalysis of zinc iodide. ... 

The same researchers found that lanthanide triflates could catalyze aldol reactions and allylations in aqueous media [10]. However, Wang et al. exploited the potential of lanthanide triflates to act as stable Lewis-acid catalysts in the aqueous imino Diels-Alder reaction [11]. This variant of the aqueous heterocycloaddition protocol also expands the scope of such reactions. The use of higher aldehydes in such reactions generally met with limited success under the conventional protocol. For example, under the standard conditions, the reaction of hexanal and benzylamine hydrochloride with cyclopentadiene in water is sluggish and affords only 4% of the Diels-Alder adducts 26 and 27 in a 2.7/1 ratio. In sharp contrast, the addition of various lanthanide(lll) triflates (0.25 M) to this reaction results in substantial increases in both the rate and yield of Diels-Alder adduct formation. In particular, use of praseodymium(iii) triflate results in a 68% yield of adducts 26 and 27 ... 

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