Lanthanides three-component reaction

Scheme 5.1-43 Three-component reaction of benzaldehyde, aniline, and diethyl phosphonate in ionic liquids, catalyzed by lanthanide triflates and indium(lll) chloride.

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... 

In a related reaction, aqueous allylation of imines has been reported by Bel-luci and co-workers using allyltributylstannane under lanthanide triflate catalysis [130]. Alternatively, the reaction can be performed without catalysis directly with the formaldehyde-generated immonium salts in aqueous media to give, in excellent yields, bis-homoallylamines and tertiary homoallylamines with primary and secondary amines, respectively [131]. These homoallylic amines were also prepared by Sc(OTf)3-catalyzed three-component reactions of aldehydes, amines and allyltributylstannane in micellar systems [132]. 

For an example of a lanthanide-promoted phenol modification with imines in organic solvents, see T.S. Huang, C.J. Li, Synthesis of amino acids via a three-component reaction of phenols, glyoxylates and amines, Tetrahedron Lett. 2000, 41, 6715. 

The Kabachnik-Fields reaction is an effective means of preparing biologically active a-amino phosphonates [64]. It involves the three component reaction of an aromatic aldehyde, an aniline, and diethylphosphite. The reaction has recently been performed using microwave irradiation with [BMIM]PF6, [BMIM]SbF6, [BMIM]BF4, and DMF as solvents and lanthanide triflates as catalysts (Scheme 7.18) [65]. The reactions were performed using a domestic microwave oven and pulsed irradiation. Catalyst activity in the ionic liquids was found to be higher than or comparable with that in DMF. It was also found that catalyst activity varied depending on the ionic liquid used. For example, Yb(OTf)3 was very active in [BMIM]BF4 but Sc(OTf)3 was more active in [BMIMjPFe. Excellent product yields were obtained. 

Moreover, Feng and coworkers reported in 2009 an enantioselective variant of this three-component reaction using metal catalysis [215]. After screening several ligands and lanthanides (Ln), Af,Af -dioxide-Sc(III) complex 82 was found to be the most efficient in the reaction of aromatic aldehydes, 2-aminophenol, and diphenyl phosphite (Scheme 12.29). The corresponding a-amino... 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

The lanthanide triflate remains in the aqueous phase and can be re-used after concentration. From a green chemistry viewpoint it would be more attractive to perform the reactions in water as the only solvent. This was achieved by adding the surfactant sodium dodecyl sulfate (SDS 20 mol%) to the aqueous solution of e.g. Sc(OTf)3 (10 mol%) [145]. A further extension of this concept resulted in the development of lanthanide salts of dodecyl sulfate, so-called Lewis acid-surfactant combined catalysts (LASC) which combine the Lewis acidity of the cation with the surfactant properties of the anion [148]. These LASCs, e.g. Sc(DS)3, exhibited much higher activities in water than in organic solvents. They were shown to catalyze a variety of reactions, such as Michael additions and a three component a-aminophosphonate synthesis (see Fig. 2.44) in water [145]. 

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. 

Aminoalkyl and Related Acids. - Further development of the classical three component approach to aminoalkylphosphonates (the Kabachnik-Fields reaction) has been reported. The reaction of aldehydes, hydroxylamines and dimethyltrimethylsilyl phosphite using lithium perchlorate/diethyl ether as a catalyst gives N-trimethylsilyloxy-a-aminophosphonate derivatives. The catalytic activities of various lanthanide triflates as well as indium trichloride have been examined for the Kabachnik-Fields type reactions of aldehydes, amines and the phosphorus nucleophiles HP(0)(0Et)2 and P(OEt)3 in ionic liquids. TaCb-Si02 has been utilized as an efficient Lewis acid catalyst for the coupling of carbonyl compounds, aromatic amines and diethyl phosphite to produce a-... 

Sc(OTf)3 and Yb(( ) l r), are quite valuable catalysts of the aza-DA reaction of 102 [204] (Scheme 10.113). Wifh these catalysts, three-component coupling of aldehydes, anilines, and 102 proceeds smoothly [304]. Sc(OSO2C8Fi7)3 enables an efficient aza-DA reaction in supercritical CO2 [305]. Cationic lanthanide complexes, [(C5Me5)2Ce][BPh4] and fhe corresponding Sm and La complexes, have high catalytic activity in the HDA reaction of 102 with aromatic aldehydes [306]. 

Additives that can be added to aqueous reactions include Lewis acids, which have roles as catalysts in organic transformations, mainly in Diels-Alder reactions [24]. A number of Lewis acids which can be used in water have been described, such as nitrates, for example, Cu(N03)2 and Zn2 +, Ni2 +, Co2+ analogs [25], lanthanide triflates, Ln(OTf)3 [26], and others, including indium trichloride [27]. Increased yields and product selectivities have been observed in several systems. A typical example is the three-component hetero-Diels-Alder reaction catalyzed by lanthanide triflate (Equation 4.14). Lanthanide triflates were used in the pH range 5-7, and when no Ln (OTf)3 was added, the product was isolated in only 4% yield however, with added lanthanide catalyst the yield was increased to 64% [28]. 

Moreover, the three-component coupling reactions proceeded smoothly in aqueous solution, and commercial formaldehyde water solution could be used directly. Most lanthanide triflates tested were effective in the three-component coupling reactions (Table 23). These reactions provide very useful routes for the synthesis of pyridine and quinoline derivatives. 

Thus, a new type of Lewis acid, lanthanide triflates, is quite effective for the catalytic activation of imines, and has achieved imino Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between aldehydes, amines, and dienes or alkenes were successfully carried out by using Ln(OTf)3 as catalysts to afford pyridine and quinoline derivatives in high yields. The triflates were stable and kept their activity even in the presence of water and amines. According to these reactions, many substituted pyridines and quinolines can be prepared directly from aldehydes, amines, and dienes or alkenes. A stepwise reaction mechanism in these reactions was suggested from the experimental results. 

It was recently found that lanthanide triflates are excellent catalysts in achiral 1,3-di-polar cycloadditions between nitrones and alkenes and also in three-component coupling reactions of aldehydes, hydroxylamines, and alkenes Kobayashi S, Akiyama R,... 

The effectiveness of lanthanide Lewis acid in Mannich-type reaction was further highlighted by three-component coupling reaction of aldehydes, amines, and enol silyl ethers [7]. With MS 4A or MgS04 as dehydrating agent, 5-10 mol% ofYb(OTf)3 worked well to afford corresponding -amino ketone and esters in good to excellent yield (Table 13.3). It should be noted that the present reaction conditions were... 

Considering the water tolerance of lanthanide Lewis acids, a logical extension of the above-mentioned three-component coupling reaction is the reaction in aqueous media. Kobayashi et al. reported Mannich-type reaction of aldehydes, aniline derivative, and methyl enol ethers with 10mol% of Yb(OTf)3 in THF/H2O solvent system (Table 13.4) [8]. Applicability of commercially available aqueous formaldehyde and chloroacetaldehyde solution is of particular importance from the synthetic point of view (entries 1-3). A wide variety of aldehydes were transformed... 

Wang reported three-component coupling reaction of aldehydes, amines, and dienes by lanthanide triflate catalyzed aza-Diels-Alder reaction in water [35, 36]. Among lanthanide triflates screened, lanthanum, praseodymium, neodymium, and ytterbium triflate were found to be effective (Table 13.16). It is worth noting that aqueous formaldehyde could be employed as substrate. These reaction conditions were applied in the synthesis of aza-sugars. 

Table 13.16 Three-component Aza-Diels-Alder reaction catalyzed by Lanthanide triflate...

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... 

Kobayashi et al. were the first to report the use of lanthanide triflates as catalysts in imino Diels-Alder reactions [9], The successful three-component cyclocondensation of an aldehyde, amine and diene in acetonitrile was realized in the presence of lanthanide triflates as the Lewis-acid catalyst. This process is reminiscent of the protonated iminium-ion-based methodologies whereby the coordinated imine formation and [4+2] cycloaddition occur in one pot. 

Bearing in mind the usefulness and efficiency of one-pot procedures, three-component coupling reactions between aldehydes, amines and alkenes via imine formation and imino Diels-Alder reactions were examined by using lanthanide triflate as a catalyst. 

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