A-Amino acids by asymmetric

The use of rhodium catalysts for the synthesis of a-amino acids by asymmetric hydrogenation of V-acyl dehydro amino acids, frequently in combination with the use of a biocatalyst to upgrade the enantioselectivity and cleave the acyl group which acts as a secondary binding site for the catalyst, has been well-documented. While DuPhos and BPE derived catalysts are suitable for a broad array of dehydroamino acid substrates, a particular challenge posed by a hydrogenation approach to 3,3-diphenylalanine is that the olefin substrate is tetra-substituted and therefore would be expected to have a much lower activity compared to substrates which have been previously examined. 

The preparation of optically pure a-amino-acids by asymmetric hydrogenation of their a,/S-unsaturated derivatives catalysed by chiral rhodium(l) diphosphine complexes continues to be actively pursued. In an outstanding paper, Fryzuk and Bosnich have described the preparation and use of the rhodium(l) complex of (i )-l,2-bis(diphenylphosphino)propane ( R-prophos ) which catalyses the reduction of (Z)-N-acylaminoacrylic acids to (5)-a-amino-acids in ca. 90%... 

Synthesis of Chiral a-Amino Acids by Asymmetric Reductive Amination of Keto Acid Substrates In 2003, Rh-Deguphos catalyzed enantioselective reductive amination of a-keto acids 106 with benzylamine (BnNH2)... 

Dondoni, A. Massi, A. (2006) Design and Synthesis of New Classes of Heterocyclic C-Glycoconjugates and Carbon-Linked Sugar and Heterocyclic Amino Acids by Asymmetric Multicomponent Reactions (AMCRs). Accounts of Chemical Research, 39, 451M63. 

Asymmetric Synthesis of a-Amino Acids by the Alkylation of Pseudoephedrine Glycinamide. Preparation of L-Allylglycine and N-Boc L-Allylglycine. 

Dondoni A, Massi A (2006) Design and synthesis of new classes of Heterocyclic C-glycoconjugates and carbon-linked sugar and heterocyclic amino acids by asymmetric multicomponent reactions (AMCRs). Acc Chem Res 39 451-463... 

Asymmetric Hydrogenation. Asymmetric hydrogenation with good enantio-selectivity of unfunctionalized prochiral alkenes is difficult to achieve.144 145 Chiral rhodium complexes, which are excellent catalysts in the hydrogenation of activated multiple bonds (first, in the synthesis of a-amino acids by the reduction of ol-N-acylamino-a-acrylic acids), give products only with low optical yields.144 146-149 The best results ( 60% ee) were achieved in the reduction of a-ethylstyrene by a rhodium catalyst with a diphosphinite ligand.150 Metallocene complexes of titanium,151-155 zirconium,155-157 and lanthanides158 were used in recent studies to reduce the disubstituted C—C double bond with medium enantioselectivity. 

Asymmetric hydrogenations are often used at this scale because the methodology accommodates a wide variety of substrates. In addition, the technique has been scaled. In-depth discussions on the synthesis of amino acids by asymmetric hydrogenations can be found in Chapters 12-15. Resolution techniques, including SMB, are also viable options. 

SYNTHESIS OF OPTICALLY ACTIVE a-AMINO ACIDS FROM a-OXO ACIDS BY ASYMMETRIC TRANSAMINATION... 

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. 

Reviews on phase-transfer catalysis for the syntheses of a-amino acids, (a) Ooi, T. and Maruoka, K. (2004) Asymmetric organocatalysis of structurally well-defined chiral quaternary ammonium fluorides. Acc. Chem. Res., 37, 526-533 (b) Maruoka, K. and Ooi, T. (2003) Enantioselective amino acid synthesis by chiral phase-transfer catalysis. Chem. Rev., 103, 3013-3028 (c) Ooi, T. and Maruoka, K. (2003) Enantioselective synthesis of a-amino acids by chiral phase-transfer catalysis. Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem.) 61, 1195-1206. 

Scheme 4.4 Preparation of a substituted 3 amino acids by asymmetric reduction of imines involving dynamic kinetic resolution. For R, see Table 4.7 Ar p MeOC6H4.

The approach can be coupled with other methods to prepare amino acids, such as to access [3-substituted a-amino acids. The methodology gives a way to prepare all four possible isomers of (3-aryl a-amino acids by a combination of asymmetric hydrogenation and the use of the deracem-ization process to invert the a-center (Scheme 9.36)." "°... 

ASYMMETRIC SYNTHESIS OF a-AMINO ACIDS BY THE ALKYLATION OF PSEUDOEPHEDRINE GLYCINAMIDE L-ALLYLGLYCINE AND... 

The asymmetric synthesis of P-hydroxy-a-amino acids by various methods has been demonstrated [104-106] because of their utility as starting materials for the total synthesis of monobactam antibiotics. 

The series on asymmetric synthesis then concludes with procedures for the preparation of enantiomerically pure products. The asymmetric syntheses of unnatural a-amino acids by the alkylation of pseudoephedrine glycin-amide is nicely exemplified by the preparation of l-ALLYLGLYCINE and N-BOC-i.-ALLYLGLYCINE. One of the advantages of this method is the ready availability of the chiral auxiliary and the mildness of the conditions required for the hydrolysis of the pseudophedrine amide to provide the a-amino acid. Biocatalytic transformations are also gaining importance in asymmetric synthesis as illustrated by the preparation of... 

This reaction was first reported by Corey and T.ink in 1992. It is an enantioselective synthesis of a -amino acids by means of the asymmetric reduction of trichloromethyl ketones from catechoiborane in the presence of either (/ )- or (5)-oxazaborolidine, followed by the treatment of the resulting alcohols with base and sodium azide and subsequently the reductive conversion of the azido group into an amino group. Therefore, this reaction is generally known as the Corey-Link reaction. Occasionally, it is also referred to as the Corey-Link amino acid synthesis, Corey-Link procedure, etc. 

Moody, C. J., Gallagher, P. T., Lightfoot, A. P. and Slawin, A. M. Z. 1999. Chiral oxime ethers in asymmetric synthesis. 3. Asymmetric synthesis of (R)-lV-protected a-amino acids by the addition of organometalUc reagents to the ROPHy oxime of cinnamaldehyde. J. Org. Chem. 64 4419-4425. 

---