Strecker method mechanisms

In Ugi four-component reactions (for mechanism, see Section 1.4.4.1.) all four components may potentially serve as the stereodifferentiating tool65. However, neither the isocyanide component nor the carboxylic acid have pronounced effects on the overall stereodiscrimination60 66. As a consequence, the factors influencing the stereochemical course of Ugi reactions arc similar to those in Strecker syntheses. The use of chiral aldehydes is commonly found in substrate-controlled syntheses whereas the asymmetric synthesis of new enantiomerically pure compounds via Ugi s method is restricted to the application of optically active amines as the chiral auxiliary group. 

R406 M. Kitagawa, K. Yamashina, S. Tojyo and D. Ulam-Orgikh, In Search for Molecules which Calculate Quantum Mechanically , Mem. Inst. Sci. Ind. Res., Osaka Univ., 2000, 57, 96 R407 A. Klein, G. Strecker, G. Lamblin and P. Roussel, Structural Analysis of Mucin - Type O - Linked Oligosaccharides , Methods Mol. Biol. (Totowa, N.J.), 2000,125,191... 

The mechanism of the Strecker reaction has received considerable attention over its lifespan.4 The conversion of a carbonyl compound into an a-amino acid, by this method, requires a two-step process. The first step consists of the three-component condensation of cyanide and ammonia with the carbonyl compound 1 to produce an intermediate, a-aminonitrile 3. The second step involves the hydrolysis of the nitrile functional group to reveal the latent carboxylic acid 4. Whereas the second step is fairly straightforward and can be done under basic or acid conditions, the first step is more involved than one may expect. The widely accepted sequence for the first step is the nucleophilic addition of ammonia to the carbonyl carbon to produce the corresponding imine derivative 2. Once formed, this initial species is captured by the cyanide anion to generate the requisite a-aminonitrile 3. 

The enantioselective Strecker reaction also succeeds with ketoimines. Thus, a-hranched amino-nitriles [94] and also unnatural amino acids [95] can he obtained hy this method. The precise mechanism of the catalysis is unclear. Kinetic investigations have previously shown, that the turnover reflects a Michaelis-Menton relationship. The imine is bonded reversibly to the catalyst. The addition of hydrogen cyanide is rate-determining. [96]... 

The very low activation energy for 2-acetyl-l-pyrroline may help explain why this volatile is found by sniffing methods in nearly every food stndied. It appears that this compound is very readily formed even nnder mild heating conditions. This fact, coupled with its extremely low sensory threshold, make its detection in foods likely. The Strecker aldehydes, isovaleraldehyde and phenylacetaldehyde, followed similar kinetics during heating. This is due to the similar mechanism of formation and the fact that they are both consumed through reaction to form 5-methyl-2-phenyl-2-hexenal [39]. 

Intensive studies using NMR methods, kinetic experiments, and computational calculations were conducted to elucidate the catalytic mechanism and observed stereoinduction [22]. The data revealed that the hydrocyanation catalyzed by 33 presumably proceed over an initial amido-thiourea catalyzed proton transfer from hydrogen isocyanide to imine 32 to generate a catalyst-bound diastereomeric iminium/cyanide ion pair. Thereby, hydrogen isocyanide, as the tautomeric form of HCN, is stabilized by the thiourea moiety of 33. The stabilization degree of the formed iminium ion by the catalyst is seen as the basis for enantioselectivity. Subsequent collapse of the ion pair and bond formation between the electrophile and the cyanide ion forms the a-amino nitrile. It should be emphasized that the productive catalytic cycle with 33 does not involve a direct imine-urea binding, although this interaction was observed both kinetically and spectroscopically in the Strecker reaction catalyzed by 25 (see above) [19],... 

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