Aminomalonate derivative

On the other hand, there is a report regarding a cascade Michael reaction followed by intramolecular nitro-Mannich (aza-Henry) reaction occurring between imides derived from diethyl aminomalonate and nitrostyrenes using thiourea 68a as catalyst (Scheme 7.63). This reaction results in a formal [3 + 2] cycloaddition between these two reagents, with this aminomalonate-derived... 

MichaeU-Henry Reaction Liu et al. and Xie et al. independently found that tertiary amine-thioureas could stereoselectively promote the addition of diethyl a-aminomalonate-derived azomethine ylides to nitroolefms, affording Michael adducts other than dipolar cycloaddition adducts as the major products. Using monofunctional chiral thioureas 140d instead of tertiary amine-thiourea catalysts, Liu et al. successfully developed a three-component [3-1-2] dipolar cycloaddition of benzaldehydes 3, diethyl a-aminomalonates 45a, and nitrostyrenes 165, resulting directly in the enantioenriched pyrrolidines 208 as the only products (Scheme 2.56) [81a] while Xie et al. efficiently converted the Michael adducts 210 to pyrrolidines 208 in high yield and maintained ee by the use of 30 equiv of 2,2,2-trifluoroethanol as the additive (Scheme 2.56) [81b]. 

Diethyl aminomalonate is a useful intermediate, lending itself to N-acylation the N-acyl derivatives may be alkylated by procedures as established for syntheses via malonic ester. 

Intermediate carbenes are also involved in the alkylation by haloforms of carbanions derived from Schiff bases of a-ammo esters [126] or aminomalonates... 

An intramolecular ring expansion of aziridine esters can be accomplished by installing an appropriate nucleophilic entity in these substrates. Conversion of the ester moiety into carboxamides derived from aminomalonate ester gives compounds 44 containing the requisite nucleophilic site in the malonate moiety (Scheme 35). 

The stereoselective Michael addition of the anion derived from diethyl acetyl-aminomalonate with chalcone has been found to be most effective under soliddiquid two-phase conditions in the absence of an added solvent [62]. For optimum overall conversion and enantiomeric excess (56% with 60% ee), A-benzyl-V-methyl-... 

With the same protocol, a heterocyclic dibenzoate 86 derived from furan in one step has been efficiently desymmetrized to provide facile entry to either D or L nucleosides (see Scheme 8E.10). As depicted in Scheme 8E.10, the catalyst derived from ligand 71 gave rise to high enantioselectivities in the alkylation with both a purine 83 and a pyrimidine 87 [62], Subsequent allylic alkylations with an achiral ligand introduced the tartronate and aminomalonate moieties to furnish enantiomerically pure Ci s-2,5-disubstituted-2,5-dihydrofurans 89 and 91, respectively. Only six steps from furan were required to synthesize the alio and talo isomers of the nucleoside skeleton of the polyoxin-nikkomycin complexes. It should be noted that the corresponding enzymatic desymmetrization of substrate 86 is impossible because the product is labile. 

Two approaches to the 2-benzazepine system, in particular the 2-benzazepinone 142, have been reported by Le Diguarher et al. The first started from (acid-catalyzed cyclization to 141 N-alkylation and carbamate deprotection then afforded 142. The second route was based on A-HOC aminomalonate 144 and 2,2 -dibromo-o-xylene, and then steps via 145 and... 

Acylaminomalonic esters and related reagents are widely used for the synthesis of a-amino acids. The method differs from those syntheses already discussed in that the amino group is incorporated into the system from the outset. A popular reagent is diethyl acetamidomalonate (35). The acetamido group can readily be introduced into the reactive methylene position in diethyl malonate by first converting the latter into the hydroxy-imino derivative (33) by reaction with nitrous acid or an alkyl nitrite (cf. Section 4.2.7, p. 413). This derivative is then reduced catalytically to diethyl aminomalonate (34) which is acetylated using acetic anhydride. 

There is no asymmetric carbon atom in aminomalonic acid molecule. When both of the carboxylic acids are substituted by esterification with different alcohols, optical isomers are generated. It is known that aminomalonic acid derivatives readily racemize in solution under ordinary conditions. L-Asp-Ama(OFn)-... 

An inspection of the IR spectra of the condensation products derived from 4-phenyl-2-ethoxy-A1 -pyrroline with diethyl aminomalonate indicates that the hydroxyimidazole (25a) predominates (82JHC193). 

Conversion of the a-cyanoketone 414 to the tosylate 415, and subsequent cyclization using diethyl aminomalonate in the presence of ethoxide, provided the aminopyrrole 416 (Scheme 51). This approach was used for the preparation of a set of related derivatives in moderate yields <2000JOC2603>. 

It would not be imprudent to say that most imine cycloadditions have been discovered unexpectedly during investigations on the generation of azo-methine ylides. As already discussed (Section II,C), imines 60, formed by the condensations of diethyl aminomalonate with aromatic aldehydes, quickly isomerize into highly stabilized azomethine ylides 61, which are all trapped by the imine 60 to give imidazolidine derivatives 217 (80TL2197). It has also been described above (Section II,E) that the iminium salt 75 (R = OMe, EWG = CN), formed in the N-alkylation of 6,7-dimethoxy-3,4-dihydroiso-quinoline with chloroacetonitrile, quickly loses a proton generating stabilized... 

The models of the renin structure indicated that the P2 subsite was narrow at the backbone region, so disubstitution of the P2 a-carbon was not recommended. Subsequent experimental evidence confirmed this prediction. In one particular series, where epimerization of the aminomalonate at the P2 site of inhibitor 4 (Table 1) was a concern [27], the a-methyl deriv-... 

The benzodiazepine derivative 246 was synthesized (yield 49%) by heating 6,8-dibromoisatoic anhydride with diethyl aminomalonate hydrochloride in the presence of triethylamine [160],... 

Shaprio described a nonoxidative method for preparing 2-substituted 4-ox-azolecarboxylic acid esters 591 (Scheme 1.161). He prepared the key intermediate, dimethyl amino[(phenylthio)methyl]malonate 588, in three straightforward steps from diethyl aminomalonate hydrochloride. Acylation of 588 gave the A-acyl derivative 589 in excellent yield, which was sequentially chlorinated and cyclized in one pot to afford the 2,4,4,5-tetrasubstituted oxazoline 590. The author noted that anhydrous conditions were required to minimize sulfoxide formation. This was the only product isolated if the chlorination cyclization sequence was carried out in a hydroxylic solvent. 

Subsequently, the one-pot organocatalytic [C+NC+CC] coupling reaction between aldehydes 204, dialkyl-2-aminomalonate 205 and a,p-unsaturated aldehydes 28 was achieved with highly chemo-and enantioselectivity by Cordova, et al Scheme 3.66 [83]. The mechanism involved the 1,3-dipolar cycloaddition of azomethine yhde and chiral iminium intermediate, via re-facial and endo-addition to give the pyrroUdine derivatives. Later, the authors reported a similar approach to 5-hydroxypyrrolidme 208 from acylaminomalonates 207 and a,P-unsaturated aldehydes 28, Scheme 3.67 [84]. 

The first catalytic asymmetric formal [3h-3] cycloaddition of isatin-3-indolyhnethanol derivatives and in situ generated azomethine ylides was recently developed to synthesize structurally diverse spiro[indoline-3,4 -pyridoindoles] 228 bearing one all-carbon quaternary stereogenic center [109]. The reaction takes place with a range of A(-substituted isatin-derived 3-indolylmethanols, aromatic aldehydes 4, and diethyl 2-aminomalonate 221 and is catalyzed with chiral phosphoric acid 227 with the bulky 9-phenanthrenyl group at the 3,3 -positions of the BINOL moiety (Scheme 2.78). 

Amere, M. Lasne, M. C. Rouden, J. Highly Enantioselective Decarboxylative Protonation of a-Aminomalonates Mediated by Thiourea Cinchona Alkaloid Derivatives Access to Both Enantiomers of Cyclic and Acyclic a-Aminoacids. Org. Lett. 2007, 9, 2621. 

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