Chiral auxiliaries Strecker amino acid synthesis

Asymmetric Strecker amino acid synthesis Addition of cyanotrimethylsilane catalyzed by ZnCl2 to optically active aldimines formed from 2,3,4,6-tetrapivaloyl-3-D-galactopyranosylamine as the chiral auxiliary can result in either (R)- or (S)-a-aminonitriles, depending on the solvent. THF or isopropanol favors (R)-dia-stereomers, whereas CHC13 favors the (S)-diastereomers. 

Asymmetric Strecker Synthesis of a-Amino Acids via a Crystallization-Induced Asymmetric Transformation Using (/Q-Phenylglycine Amide as Chiral Auxiliary... 

The synthesis of a-amino acids is important because they are used extensively in pharmaceuticals, agrochemicals, and as chiral ligands. The Strecker reaction is historically one of the most versatile ways to synthesize a-amino acids, but this method yields only 50% of a single enantiomer. Higher yields can be achieved by using chiral auxiliaries, but auxiliaries are often high in cost and low in availability. 

Several reports have employed a more traditional approach where the use of enantio-pure chiral amino auxiliaries, that, after the successful Strecker reaction, can be chemically modified to yield the free amino acids. For example, Chakraborty and co-workers have reported the highly diastereoselective addition of trimethylsilyl cyanide to a variety of a-phenylglycinol-derived benzaldimines [16]. (S)-a-Methylbenzylamine has been used as a chiral auxiliary for the asymmetric Strecker reaction [17]. (R)-Phenylglycinol has been utilized as a chiral auxiliary from the asymmetric Strecker reaction products of aldehydes in the synthesis of a,a-disubstituted amino acids [18]. (R)- and (S)-2-Amino-2-phenylethanol were used as chiral auxiliaries in the synthesis of optically pure a-arylglycines [19]. 

The synthesis of enantiopure amino-functionalized compounds such as a- and (3-amino acids or nonfunctionalized amines can be envisaged by the use of aldehydes, ketones, a- or (3-keto acids, or derivatives thereof as substrates for imine formation followed by, for example, diastereoselective Strecker reactions, reductions, or organometallic addition reactions. In the literature, diastereoselective syntheses based on a large variety of chiral auxiliaries, such as a-arylethylamines,4... 

In Ugi s four-component condensation, imine formation from an aldehyde 1 and an amine 2 is likewise the initiating step [5, 6] a carboxylic acid 9 and an isonitrile 10 are the other reaction components, which finally yield the bisamide 11. Both for this reaction and the Strecker synthesis, the galactosylamine 12 is particularly suitable for carrying out a stereoselective reaction (synthesis of 13) [4d-e, 5f. With an aminoglucopyranose as a chiral auxiliary, the stereoselectivity of the reaction can be further increased [5b]. Amino acids as condensation components yield particularly impressive results. For instance, the imino-... 

The application of an organocatalytic method for the generation of the quaternary a-aminoaldehyde shows that organocatalysis can be an attractive alternative to classical methods e.g. the auxiliary controlled Strecker synthesis. Introducing the chiral information catalytically can clearly be an advantage compared to a stoichiometric chiral pool approach, especially when the stereogenic center cannot be derived from a natural amino acid. 

Bousquet, C., Tadros, Z., Tonnel, J., Mion, L., Taillades, J. Auxiliary chiral ketones in the asymmetric synthesis of a-amino acids by Strecker reaction. Bull. Soc. Chim. Fr. 1993, 130, 513-520. 

An advantage of the substrate-based strategy is that the chiral auxiliary is still attached to the molecule after the induction reaction and so the product, 9 in this instance, can be purified as one diastereoisomer before the chiral auxiliary is removed. An example of the asymmetric Strecker reaction in practice is the synthesis of the fat amino acid 16 having an adamantyl group to increase solubility in fats and hence permeability to cell membranes.2 After purification of the amino nitrile 13 hydrolysis gives the amide 14, hydrogenation removes (and sadly destroys) the chiral auxiliary, and a final hydrolysis gives the fat amino acid 16. 

In addition to amino acids, 1,2-amino alcohols can be used as chiral auxiliaries. The synthesis of the amino acid derivative 16 outlined in Scheme 9.15 is a variation of a Strecker reaction. - Evans oxazolidinone chemistry is well documented, which allows for a wide variety of reactions to be performed with a high degree of predictability. In addition to alkylation reactions to introduce the side chain of an amino acid, the nitrogen group can also be introduced in a variety of ways, one of which is illustrated in Scheme 9.16. ... 

Kunz, H, Sager, W, Schanzenbach, D, Decker, M, Carbohydrates as chiral templates stereoselective Strecker synthesis of D-a-amino nitriles and acids using 0-pivaloylated D-galactosylamine as the auxiliary, Liebigs Ann. Chem., 649-654, 1991. 

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