Strecker synthesis, asymmetric

The asymmetric Strecker synthesis of a-amino nitriles from Schiff bases of a-methylbenzyl-aminc is improved by the use of trimethylsilyl cyanide, instead of hydrogen cyanide and by promotion of the transformation with a Lewis acid, preferably zinc chloride43. Thus, from the butyraldimine 2, the amino nitrile is synthesized with a yield of 98.5% and an ee of 68.5%. 

In asymmetric Strecker synthesis ( + )-(45,55 )-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has been introduced as an alternative chiral auxiliary47. The compound is readily accessible from (lS,25)-2-amino-l-phcnyl-l,3-propancdioI, an intermediate in the industrial production of chloramphenicol, by acctalization with acetone. This chiral amine reacts smoothly with methyl ketones of the arylalkyl47 or alkyl series48 and sodium cyanide, after addition of acetic acid, to afford a-methyl-a-amino nitriles in high yield and in diastereomerically pure form. 

Both the ureas and thioureas are highly suitable organocatalysts for the asymmetric Strecker synthesis. For example, the thiourea function was replaced by an urea function (note the opposite configurations). The organocatalysts thus obtained showed similar activity and slightly higher enantioselec-tivities with N-allyl benzaldimine (Scheme 39,74% yield with 95% ee for Ri = Bn and R2 = H). Once again, better enantioselectivity (up to 99% ee) was at-... 

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

Lastly, we consider Boesten et al. (2001) (excerpt 5E), which describes an asymmetric Strecker synthesis. Recall that the synthesis results in two diastereomers, which can be separated based on their different solubilities in water. In exercise 2.14 (chapter 2), you were asked to decide where the Discussion section began in this article. That exercise was more challenging than you may have realized. The article presents numerous results, with only a few sections of integrated discussion. 

In summary, (R)-phenylglycine amide 1 is an excellent chiral auxiliary in the asymmetric Strecker reaction with pivaldehyde or 3,4-dimethoxyphenylacetone. Nearly diastereomerically pure amino nitriles can be obtained via a crystallization-induced asymmetric transformation in water or water/methanol. This practical one-pot asymmetric Strecker synthesis of (R,S)-3 in water leads to the straightforward synthesis of (S)-tert-leucine 7. Because (S)-phenylglycine amide is also available, this can be used if the other enantiomer of a target molecule is required. More examples are currently under investigation to extend the scope of this procedure. ... 

As the last example, we present a poster Methods section based on Boesten et al. (2001) concerning the asymmetric Strecker synthesis of an a-amino acid (excerpt 9D and at the end of chapter 2). The poster Methods section presents only... 

Most commonly, a-phenylethylamine is used as chiral amine in the asymmetric Strecker synthesis. Amino acid derivatives have also been used quite successfully as chiral amines. Especially (S)-tert.-butylglycine tert.-butyl ester was proven to be a powerful chiral inductor iM>). The optical yields were as high as 96.5%. The best results were obtained in nonpolar solvents such as n-hexane 140>. 

The asymmetric Strecker synthesis was also applied in the preparation of other chiral products. In these reactions japanese chemists 141> always used amino acid derivatives as the chiral amine component which is responsible for the induction of asymmetry. 

As indicated in Scheme 14, introduction of the rp[CH(CN)NH] peptide bond surrogate into pseudopeptides 28 is carried out via a modified asymmetric Strecker synthesis by the Lewis acid catalyzed reaction of N -protected a-amino aldehydes 26 with a-amino esters 27.11791... 

Catalytic Asymmetric Strecker Synthesis of Amino Acids. 172... 

Scheme 3.23 Asymmetric Strecker synthesis using a-amido sulfones with acetone cyanohydrin.

Scheme 2. Asymmetric Strecker synthesis with cyclic dipeptide 2 (Lipton and co-workers).

Scheme 3. Asymmetric Strecker synthesis with chiral Alm-Salen catalyst 5 (Sigman and Jacobsen). TFAA = trifluoroacetic anhydride.

Scheme 4. Asymmetric Strecker synthesis with salicylimine catalyst 9 (Vachal and Jacobsen). Bn = benzyl.

Scheme 6. Asymmetric Strecker synthesis with bifunctional Lewis acid-Lewis base catalyst 14 (Shibasaki and co-workers). DDQ = 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone.

An alternative access to L-amino acids was found by using chloroform as solvent in the asymmetric Strecker synthesis with galactosyl imines [24], This interesting reverse of asymmetric induction compared to the reactions shown in Scheme 5 can be explained by considering the zinc complex A as the crucial reactive species. Due to the exo anomeric effect, which is a delocalization of the 7r-electrons into the a of the ring C-O-bond, the imines adopt the conformation represented in Scheme 8. 

Davis and Fanelli applied the sulfinimine mediated asymmetric Strecker synthesis to the enantioselective synthesis of the racemization-prone (/ )-(4-methoxy-3,5-dihydroxyphenyl)glycine (134) from 133.81 This amino acid is the central amino acid of the clinically important glycopeptide antibiotic vancomycin as well as related antibiotics. 

Davis, F. A., Reddy, R. E., Portonovo, P. S. Asymmetric Strecker synthesis using enantiopure sulfinimines a convenient synthesis of a-amino acids. Tetrahedron Lett. 1994, 35, 9351-9354. 

Ishitani, H., Komiyama, S., Hasegawa, Y., Kobayashi, S. Catalytic Asymmetric Strecker Synthesis. Preparation of Enantiomerically Pure a-Amino Acid Derivatives from Aidimines and Tributyitin Cyanide or Achirai Aidehydes, Amines, and Hydrogen Cyanide Using a Chiral Zirconium Catalyst. J. Am. Chem. Soc. 2000,122, 762-766. 

Enders, D., Moser, M. Asymmetric Strecker synthesis by addition of trimethylsilyl cyanide to aldehyde SAMP-hydrazones. Tetrahedron Lett. 2003,44, 8479-8481. 

Stout, D. M., Black, L. A., Matier, W. L. Asymmetric Strecker synthesis isolation of pure enantiomers and mechanistic implications. J. Org. Chem. 1983,48, 5369-5373. 

Cyanations. Aluminum complexes with diarylphosphine oxide groups possev cyanation of aldehydes and imines- with in a manner analogous to the Reisser asymmetric Strecker synthesis is applic reactivity of Me SiCN than HCN in the p catalytic amount while supplying stoichica... 

Cyanadons. Aluminum complexes of BINOLs (1) that are armed at C-3 and C-3 with diarylphosphine oxide groups possess both Lewis acid and base centers. Asymmetric cyanation of aldehydes and mines with MeaSiCN, and of quinolines and isoquinolines in a manner analogous to the Reissert reaction is successful (ee 70-90%). The asymmetric Strecker synthesis is applicable to conjugated aldimines and the higher reactivity of Me SiCN than HCN in the presence of 10 mol% of PhOH enables its use in catalytic amount while supplying stoichiometric HCN as the cyanide source. 

The derivative, silylated at both oxygens, 10 is named (S.S)-BISPAD13 and is also used for the preparation of dihydrooxazoles (Section D.1.1.1.2.). (S.S)-PAD denotes the 1,3-dioxane formed from the aminodiol and acetone13 which is used in the asymmetric Strecker synthesis. 

An example of an asymmetric Strecker synthesis is the reaction between (S)-1-phenylethylamine, benzylmethyl ketone and NaCN to give... 

Other syntheses of aromatic and heteroaromatic amides have appeared. (R)-(+)-2-Methyl-3-phenylalanine has been synthesized by a four-step asymmetric Strecker synthesis using... 

For the synthesis of the 2,3,4,6-tetra-O-pivaloyl-p-D-galactopyranosylamine 88 as the chiral template in the asymmetric Strecker synthesis [34], pivaloylated galactopyranosyl fluoride 92 [35] was activated with BF3-etherate and then reacted with trimethylsilyl azide [36] to give o-galactopyranosyl azide 93 (Fig. 8.26) with a surprising preponderance of the a-anomer. If the reaction was carried out with SnCl4... 

For some selected examples, see (a) Y. Perez-Fuertes, J. E. Taylor, D. A. TickeU, M. F. Mahon, S. D. Bull, T. D. James, J. Org. Chem. 2011, 76, 6038-6047. Asymmetric Strecker synthesis of a-arylglycines. (b) J. R. Donald, R. R. Wood, S. F. Martin, ACS Comb. Sci. 2012,14,135-143. Application of a sequential multicomponent assembly process/Huisgen cycloaddition strategy to the preparation of libraries of 1,2,3-triazole-fused 1,4-benzodiazepines, (c) L. Y. V. Mendez, V.V. Kouznetsov, Curr. Org. Chem. 2013, 10, 969-973. First girgensohnine analogs prepared through InClj-catalyzed Strecker reaction and their bioprospection. 

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