Diels-Alder reaction amino acid salts

Amino Acid Salts as Lewis Acids for Asymmetric Diels-Alder Reactions... 

Figure 5-7. Transition state of amino acid salt catalyzed Diels-Alder reaction. Reprinted with permission by Am. Chem. Soc., Ref. 34.

TABLE 5-3. Solvent Effect of Amino Acid Salt-Catalyzed Diels-Alder Reaction... 

Also the use of moisture stable ionic liquids as solvents in the Diels-Alder reaction has been carried out, and in all examples an enhanced reaction rate was observed [182,183]. The application of pyridinium-based ionic liquids allowed the utilization of isoprene as diene [184]. The chiral ionic liquid [bmim][L-lactate] was used as a solvent and accelerated the reaction of cyclopentadiene and ethyl acrylate, however, no enantiomeric excess was observed [183]. In addition several amino acid based ionic liquids have been recently tested in the Diels-Alder reaction. Similar exo. endo ratios were found but the product was obtained as racemate. The ionic liquids were prepared by the addition of equimolar amounts of HNO3 to the amino acids [185]. Furthermore, an enantiopure imidazolium salt incorporating a camphor motive was tested in the Diels-Alder reaction. No enantiomeric excess was found [186]. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

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]. 

B3LYP/6-311G (PCM) calculations have shown that the 4 + 2-cycloaddition of cyclopentadiene and -/ -nitrostyrene in nitromethane solution proceeded in a stepwise mechanism. Sulfanyl-methylene-5(4//)-oxazolones and -sulfanyl-a-nitroacrylates have been used as dienophiles in the Diels-Alder reactions to synthesize norbornene/ane amino acid derivatives suitable for peptide synthesis. Organoammonium salts of chiral triamine catalyse the Diels-Alder reaction of a-(carbamoylthio)acroleins with acyclic 1,3-dienes to produce cyclohexenes with sulfur-containing chiral quaternary carbons.The helical-chiral hydrogen-donor... 

The amino acid derived chiral oxazolidinone 188 is a very commonly used auxiliary in Diels-Alder and aldol reactions. However, its use in diastereoselective 1,3-dipolar cycloadditions is less widespread. It has, however, been used with nitrile oxides, nitrones, and azomethine ylides. In reactions of 188 (R = Bn, R =Me, R = Me) with nitrile oxides, up to 92% de have been obtained when the reaction was performed in the presence of 1 equiv of MgBr2 (303). In the absence of a metal salt, much lower selectivities were obtained. The same observation was made for reactions of 188 (R = Bn, R = H, R = Me) with cyclic nitrones in an early study by Murahashi et al. (277). In the presence of Znl2, endo/exo selectivity of 89 11 and up to 92% de was observed, whereas in the absence of additives, low selectivities resulted. In more recent studies, it has been shown for 188 (R =/-Pr, R = H, R =Me) that, in the presence of catalytic amounts of Mgl2-phenanthroline (10%) (16) or Yb(OTf)3(20%) (304), the reaction with acyclic nitrones proceeded with high yields and stereoselectivity. Once again, the presence of the metal salt was crucial for the reaction no reaction was observed in their absence. Various derivatives of 188 were used in reactions with an unsubstituted azomethine ylide (305). This reaction proceeded in the absence of metal salts with up to 60% de. The presence of metal salts led to decomposition of the azomethine ylide. 

Dihydropyran derivatives were synthesized as follows 2-(tosyloxymethyl)-3,4-dihydro-2H-pyran was prepared by the reaction of tosyl chloride with 2-(hydroxymethyl)-3,4-dihydro-2H-pyran, which was obtained by reduction of 2-formyl-3,4-dihydro-2H-pyran, Diels-Alder product of acrolein, with the aid of NaBH4. Syntheses of 2-(nucleic acid base methyl)-3,4-dihydro-2H-pyrans were achieved by treatment of sodium salts of the corresponding nucleic acid bases with 2-(tosyloxymethyl)-3,4-dihydro-2H-pyran in dimethylformamide. In order to facilitate its copolymerization with maleic anhydride, the amino group of adenine was blocked by acetyl group. 

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