Diels-Alder reaction Of imines

Polymer-supported BINOLs thus prepared were treated with Zr(Ot-Bu)4 to form polymer-supported zirconium 20. In the presence of 20 mol% of various zirconium 20, the model aza Diels-Alder reactions of imine Id with Danishefsky s diene (7a) were performed results from selected examples are shown in Table 5.8. Whereas the 4-t-butylphenyl group resulted in lower enantiomeric excess (ee), higher ee were obtained when 3,5-xylyl, 4-biphenyl, 4-fluorophenyl, and 3-tri-... 

Lanthanide triflates catalyze the Diels-Alder reaction of imines, generated from anilines and aldehydes, with both dienes and alkenes [26]. Thus N-benzyl-ideneaniline in the presence of Yb(OTf)3 (Scheme 6.16) reacts in organic solvent with open-chain dienes, such as Danishefsky s diene, to give tetrahy-dropyridine derivatives, while with cyclopentadiene and vinylethers and vinylthioethers it works like azadiene in both organic solvent and aqueous medium, affording tetrahydroquinoline derivatives. 

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... 

Rare-earth-metal triflates are efficient catalysts in Diels-Alder reactions, and Sc(OTf)3 is clearly more effective than Ln(OTf)3 as a catalyst.45,53-55 In the presence of 10mol.% Y(OTf)3 or Yb(OTf)3, only a trace amount of the adduct was obtained in the Diels-Alder reaction of methyl vinyl ketone (MVK) with isoprene. In contrast, the reaction proceeded smoothly to give the adduct in 91% yield in the presence of 10mol.% Sc(OTf)3 (Scheme 13).45 Sc(OTf)3 has also proved to be an efficient catalyst for the Diels-Alder reaction of imines (aza Diels-Alder reactions).56,57... 

Figure 931b. Hetero-Diels-Alder reaction of imines.

Enantiomerically pure pipecolic acid (6) is accessible essentially by two well-established synthetic routes (i) cyclization of l- or D-lysine by reaction with disodium nitrosyl-pentacyanoferrate(II) with preservation of configuration at C2 215 216 (ii) ring closure of A ,Ae-bis(A-nitroso-A-tosyl) derivatives of l- or D-lysine, again with retention of chirality at C2. 217 Stereoselective synthesis of pipecolic acid derivatives, substituted in position 4, is achieved using the aza-Diels-Alder reaction of imines with dienes 218-220 or via an ene-iminium cyclization. 221 222 ... 

Kobayashi, S., Araki, M., Ishitani, H., Nagayama, S. and Hachiya, I., Activation of imines by rare earth metal triflates. Ln(OTf)3- or Sc(OTf)3-catalyzed reactions of imines with silyl enolates and Diels-Alder reactions of imines, Synlett, 1995, 233-234. 

Substituted tetrahydropyridines 134 have been recently prepared via an interesting one-pot transformation involving the Aza Diels-Alder reaction of imines 132 with enamines 133 (Scheme 26) [62]. The enamine adducts were prepared from the reaction of anilines 129 with the Knoevenagel products of 130 and 131. 

The Brpnsted acid-assisted chiral Lewis acid (BLA) 28, prepared from a 1 2 molar ratio mixture of a trialkylborate and optically pure binaphthol, is also an excellent chiral promoter for the aza Diels-Alder reaction of imines with Danishefsky dienes (Eqs 44 and 45). Enantioselectivity and double diastereodifferentiation in reactions employing chiral 28 are slightly better than those using chiral 27 [41]. 

Catalysts for hetero Diels-Alder reactions of imines 03MI89. 

Application of a hetero Diels-Alder reaction of imines in the syntheses of natural products 03MI96. 

The aqueous aza-Diels-Alder reaction of imines has recently been developed. (S)-Phenyleth-ylamine hydrochloride (1) reacts with aqueous formaldehyde (2) and the resulting imine 3 undergoes a [4 + 2] cycloaddition with cyclopentadiene (4) to give adduct 5 with d.r. 70 3067. 

The diastereoselective hetero-Diels Alder reaction of imines leads to enantiomerically pure 2-substituted piperidines, important synthons for the synthesis of nitrogen-containing natural products. 2,3,4,6-Tetra-0-pivaloyl-/ -D-galactopyranosylimines 1, easily synthesized from the respective 1-galactosamine. react with isoprene (2a), 2,3-dimethyl-l,3-butadiene (2b) and ( )-l-methoxy-3-trimethylsiloxy-l,3-butadiene (4) under zinc chloride etherate catalysis71. Adducts 3 are obtained with moderate to good diastereoselectivities, while adduct 5 is produced with a diastereomeric ratio of greater than 95 5. Adduct 5 can then be converted into the alkaloid (S)-anabasin. 

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. 

Thus, catalytic asymmetric aza Diels-Alder reactions of imines with alkenes have been developed using a chiral lanthanide Lewis acid, to afford 8-hydroxy-quinoline derivatives in high yields with high diastereo- and enantioselectivi-ties. Characteristic points of this reaction are as follows. 

Thus, this new type of Lewis acid, the Ln(OTf)3, is quite effective for the catalytic activation of imines, and has achieved aza 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... 

Greico and Kaufman used a similar strategy, this time involving the Diels-Alder reaction of 3-vinylindole with an appropriately tethered imine, to construct the pentacyclic ebumamonine structure in a very efficient manner [108] (Scheme 65). At first attempt, the thermal Diels-Alder reaction of imine 307 in 1,2-dichlorobenzene at 180°C afforded the cycloadduct 308 in only 32% yield, and without the formation of ebumamonine (309). Next, cycloadditions under acidic conditions were examined. The optimal conditions were found to involve conducting the reaction at 5 M lithium perchlorate-diethyl ether with 0.1 equivalent of cam-phorsulfonic acid, thus affording the Diels-Alder product 308 in 96% yield. 

Asymmetric Diels-Alder reaction of imines. Diels-Alder reactions of imines generally require an acyl or tosyl activating group on nitrogen, but can be effected in the presence of trifluoroacetic acid (1 equiv.) and a catalyst such as BF3 etherate or water (0.03 equiv.). Under these conditions, the imine BzlN=CHCOOR, formed from benzylamine and an alkyl glyoxylate, reacts with simple dienes to form derivatives of pipecolic acid in high yield (equation I). This aza-Diels-Alder reaction has been used... 

Lewis acid-catalyzed (EtAlCla, ZnClz) aza Diels-Alder reaction of imines derived from amino acid esters or carbohydrates with Danishefsky s diene provide precursors of chiral piperidine alkaloids. When using imines derived from 0-pivaloylated glycosylamines and ZnCl2 as Lewis acid, highly diastereoselective tandem-Mannich-Michael reactions are observed. The carbohydrate moiety is easily removed by treatment with HCl/MeOH. By employing galactopyranosylamine or arabinosylamine derivatives both enantiomeric series are readily available. 

A review of formal aza-Diels-Alder reactions of imines with e-rich dienes and enones, in the presence of Lewis acids/Brpnsted acids/organocatalysts, has been presented. Bifunctional A-acyl aminophosphine catalysts (75) are effective asymmetric organocatalysts in the hetero-4- -2-cycloaddition of a-substituted allenoates with tosylaldimines to produce optically active tetrahydropyridines. The Brpnsted acid-catalysed aza-Diels-Alder reactions of cyclopentadiene with iminoacetates possessing two chiral auxiliaries yielded 2-azabicyclo[2.2.1]hept-5-ene cycloadducts with high exo-selectivities. ... 

The aza-Diels-Alder reaction of imines with diene of Danishefsky is an important route to 2,3-dihydro-4-pyridones. A number of Lewis acids have been used to catalyze the reaction in organic solvents. In water the reaction was realized by acid catalysis via iminium salts or by Bronsted acids. The montmorillonite K-10 catalyzed this cycloaddition in water or in aqueous acetonitrile in excellent yield. Recently Kobayashi has performed the reaction in water at room temperature under neutral conditions in two (imine - - diene) or three (aldehyde -b amine -b diene) component versions by using sodium triflate as catalyst. Imine intermediates from the indium-mediated reaction, in aqueous medium at 50° C, between aromatic nitro compounds and 2,3-dihydrofuran undergo aza-Diels-Alder cycloadditions to give tetrahydroquinoline derivatives in good overall yields. ... 

Thus, we have developed catalytic asymmetric aza Diels-Alder reactions of imines with alkenes using a chiral lanthanide Lewis acid, to afford 8-hydroxyquinoline derivatives in high yields with high diastereo- and enan-tioselectivities. The characteristic points of this reaction are as follows, (i) Asymmetric aza Diels-Alder reactions between achiral azadienes and dienophiles have been achieved using a catalytic amount of a chiral source, (ii) The unique reaction pathway, in which the chiral Lewis acid activates not dienophiles but dienes, is revealed. In most asymmetric Diels-Alder reactions reported using chiral Lewis acids, the Lewis acids activate dienophiles [64, 65]. However, inverse electron-demand asymmetric Diels-Alder reactions of 2-pyrone derivatives have been reported [72]. (iii) A unique lanthanide complex including an azadiene and an additive, which is quite different from the conventional chiral Lewis acids, has been developed. 

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