Cycloaddition lanthanide catalyzed

Many other groups further studied the utility of bis(oxazolines) including Ikeda s use of biaryl bis(oxazolines) such as 250 (Fig. 9.75) in the zinc-catalyzed asymmetric alkylation of benzaldehyde with diethylzinc. " This reaction proceeded in yields up to 92% with ee up to 88%. Kodama and co-workers used a biaryl bis(oxazoline) ligand, namely, [l,l -]binaphthalenyl-2,2 -diol (BlNOL)-box 251, in the lanthanide-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to alkenes. ... 

Both Diels-Alder and hetero-Diels-Alder reactions can be rendered stereoselective using l copper(II) salts, but inferior levels of stereoselection were observed relative to other pybox derivatives. Lanthanide-catalyzed 1,3-dipolar cycloaddition also exhibited moderate (61%) enantioselection. ... 

Lanthanide /3-diketonates have been used as catalysts in Diels-Alder reactions. The first example of a lanthanide-catalyzed cycloaddition was the dimerization of spiro[2.4]hepta-4,6-diene by [Eu(tfn)3] (Morrill et al., 1975) (scheme 2). In the absence of the europiitm(lll) complex no dimerization took place. Because of the mild experimental conditions, this catalyst has potential in Diels-Alder reactions where acid labile components are combined. An example is the cycloaddition of cyclopentadiene with acrolein (Danishefsky and Bednarski, 1985). 

There have been few mechanistic studies of Lewis acid-catalyzed cycloaddition reactions with carbonyl compounds. Danishefsky et ah, for example, concluded that the reaction of benzaldehyde 1 with trans-l-methoxy-3-(trimethylsilyloxy)-l,3-di-methyl-1,3-butadiene (Danishefsky s diene) 2 in the presence of BF3 as the catalyst proceeds via a stepwise mechanism, whereas a concerted reaction occurs when ZnCl2 or lanthanides are used as catalysts (Scheme 4.3) [7]. The evidence of a change in the diastereochemistry of the reaction is that trans-3 is the major cycloaddition product in the Bp3-catalyzed reaction, whereas cis-3 is the major product in, for example, the ZnCl2-catalyzed reaction - the latter resulting from exo addition (Scheme 4.3). 

Different chiral transition- and lanthanide-metal complexes can catalyze the cycloaddition reaction of unactivated and activated aldehydes with especially activated... 

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

Different main-group-, transition- and lanthanide-metal complexes can catalyze the cycloaddition reaction of activated aldehydes with activated and non-activated dienes. The chiral metal complexes which can catalyze these reactions include complexes which enable substrates to coordinate in a mono- or bidentate fashion. 

Because ketones are generally less reactive than aldehydes, cycloaddition reaction of ketones should be expected to be more difficult to achieve. This is well reflected in the few reported catalytic enantioselective cycloaddition reactions of ketones compared with the many successful examples on the enantioselective reaction of aldehydes. Before our investigations of catalytic enantioselective cycloaddition reactions of activated ketones [43] there was probably only one example reported of such a reaction by Jankowski et al. using the menthoxyaluminum catalyst 34 and the chiral lanthanide catalyst 16, where the highest enantiomeric excess of the cycloaddition product 33 was 15% for the reaction of ketomalonate 32 with 1-methoxy-l,3-butadiene 5e catalyzed by 34, as outlined in Scheme 4.26 [16]. 

Scandium triflate [33] is a more active catalyst than the lanthanide triflates and the cycloadditions can also be carried out in aqueous media (Chapter 4). The catalyst is easily recovered from the aqueous layer after the reaction is completed, and can be reused. Some of the cycloadditions carried out in DCM and catalyzed by Sc(OTf)3 are summarized in Table 3.2. 

The 2-pyrones can behave as dienes or dienophiles depending on the nature of their reaction partners. 3-Carbomethoxy-2-pyrone (84) underwent inverse Diels-Alder reaction with several vinylethers under lanthanide shift reagent-catalysis [84] (Equation 3.28). The use of strong traditional Lewis acids was precluded because of the sensitivity of the cycloadducts toward decarboxylation. It is noteworthy that whereas Yb(OTf)j does not catalyze the cycloaddition of 84 with enolethers, the addition of (R)-BINOL generates a new active ytterbium catalyst which promotes the reactions with a moderate to good level of enantio selection [85]. 

The aqueous aza-Diels-Alder reaction of an aldehyde and an amine hydrochloride with a diene is catalyzed by lanthanide(III) trifluoromethane sulfonates (Ln(OTf)3, triflates [24]). Some examples are reported in Schemes 6.12 and 6.13. With respect to uncatalyzed reactions, the lanthanide catalyst allows milder reaction conditions, increases the reaction yield and does not affect the diaster-eoselectivity of the reaction, but influences the regiochemistry as in the cycloaddition of 25 with 1,3-dimethyl-1,3-butadiene (Schemes 6.10 and 6.12). These results have been applied [24b-d] to the synthesis of azasugars (Scheme 6.14). 

In the presence of a catalytic amount of chiral lanthanide triflate 63, the reaction of 3-acyl-l,3-oxazolidin-2-ones with cyclopentadiene produces Diels-Alder adducts in high yields and high ee. The chiral lanthanide triflate 63 can be prepared from ytterbium triflate, (R)-( I )-binaphthol, and a tertiary amine. Both enantiomers of the cycloaddition product can be prepared via this chiral lanthanide (III) complex-catalyzed reaction using the same chiral source [(R)-(+)-binaphthol] and an appropriately selected achiral ligand. This achiral ligand serves as an additive to stabilize the catalyst in the sense of preventing the catalyst from aging. Asymmetric catalytic aza Diels-Alder reactions can also be carried out successfully under these conditions (Scheme 5-21).19... 

Soluble lanthanide complexes such as Eu(fod)3 and Yb(fod)3 catalyze the cycloaddition reaction leaving the primary Diels-Alder products (6). These compounds can be converted on treatment with triethylamine in methanol to ulosides (8) (see Scheme 5) [30]. 

Cycloadditions with enol ethers The Diels-Alder reaction of vinyl ethers with a,(3-unsaturated aldehydes proceeds at room temperature when catalyzed by the related lanthanide Yb(fod),. An example is the reaction of crotonaldehyde with ethyl vinyl ether (equation I). 

There is the potential with some substrates that the Lewis acidity of the lanthanide ion can catalyze a reaction. For example, the addition of Eu(hfc)3 to a racemic mixture of dimethylpenta-2,3-dienoates (39) caused an enrichment of the (5 )-isomer °. Over nine days the mixture converted to an 89 11 mixture. Lanthanide tris( S-diketonates) are well known catalysts for Diels-Alder reactions, and NMR spectroscopy of the reactants with Eu(hfc)3 was used to understand the stereoselectivity of the europium-catalyzed cycloadditions . ... 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

A conceptually different [4-1-2] cycloaddition catalyzed by a chiral lanthanide complex has been disclosed. The inverse electron demand Diels Alder reaction of 3-methoxycarbonyl-2-pyrone (67) and enol ethers or sulfides [135] was catalyzed by a chiral ytterbium(III) triflate-binaphthol complex in the presence of diisopropylethylamine (Scheme 51) [136]. Thermal decarboxylations of bicyclic lactones such as 68 are known to yield dienes which may undergo subsequent pericyclic reactions [137] thus, the adducts of this process are potentially useful chiral building blocks. The nature of the substituent on the 2k component was found to be crucial for the realization of high enantioselectivity. 

Aqueous aza Diels-Alder reactions were first described in cycloadditions of imini-um salts and dienes [38], Likewise, iminium salts derived from amino acids react in excellent yields in aqueous medium [39]. Such an aqueous aza Diels-Alder reaction was found to be catalyzed by lanthanide(III) trifluoromethanesulfonates [40]. 

In 1984 Danishefsky and Bednarski demonstrated that lanthanide(III) complexes catalyze the cycloaddition of activated dienes with aldehydes. The stereoselectivity increases climatically when using these catalysts. When diene (8), for example, reacts with a variety of aldehydes with Eu(fc )3 as catalyst virtually complete cis (endo) selectivity is observed (Table 6). The aldehydes that function as dienophiles can be aliphatic (acetaldehyde and hexanal) or aromatic (benzaldehyde and furfural). 

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]. 

The hydroamination of olefins has been shown to occur by the sequence of oxidative addition, migratory insertion, and reductive elimination in only one case. Because amines are nucleophilic, pathways are available for the additions of amines to olefins and alkynes that are unavailable for the additions of HCN, silanes, and boranes. For example, hydroaminations catalyzed by late transition metals are thought to occur in many cases by nucleophilic attack on coordinated alkenes and alkynes or by nucleophilic attack on ir-allyl, iT-benzyl, or TT-arene complexes. Hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of an olefin into a metal-amide bond. Finally, hydroamination catalyzed by dP group 4 metals have been shown to occur through imido complexes. In this case, a [2+2] cycloaddition forms the C-N bond, and protonolysis of the resulting metallacycle releases the organic product. 

Hetero Diels-Alder reactions are a good entry for the preparation of intermediates for total synthesis of sugars. The lanthanide catalysts allow to work with labile reactants and adducts with an excellent stereo-chemical control. Moreover Danishefsky found (56) that a chiral europium shift reagent (Eu(hfc) ) is able to catalyze asymmetric cycloaddition (eq. 40] ). ... 

Dipolar cycloaddition provides a useful and direct process to construct 5-membered heterocycles. Kobayashi et al reported that a three-component assembly of aldehydes, hydroxylamines, and electron-deficient olefins via 1,3-dipolar cycloaddition catalyzed by lanthanide triflate [38]. With 20mol% of Yb(OTf)3, the reaction proceeded smoothly to afford isoxazolidines in good to excellent yield and... 

S. Kobayashi, R. Akiyama, Lanthanide triflate-catalyzed 1,3-dipolar cycloaddition reactions of polymer-supported nitrones with alkenes for the preparation of diverse 2-isoxazoline derivatives. Tetrahedron Lett. 1998, 39, 9211 9214. 

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