Synthesis of α-Amino Acids and Derivatives
A Zn/Cu(OTf)2-mediated addition of alkyl bromides to dehydroalanine (Dha) derivatives including dipeptides and tripeptides provides selective and biocompatible access to various amino acid units in good to high yields in an aqueous medium.
J.-A. Shin, J. Kim, H. Lee, S. Ha, H.-Y. Lee, J. Org. Chem., 2019, 84, 4558-4565.
By condensing α-3° primary amines with an electron-rich aryl aldehyde, an oxidation and deprotonation event is enabled, which generates a key imidoyl radical intermediate. A subsequent β-scission event liberates alkyl radicals for coupling with electron-deficient olefins for the generation of unnatural γ-quaternary amino acids and other valuable synthetic targets.
M. A. Ashley, T. Rovis, J. Am. Chem. Soc., 2020, 142, 18310-18316.
Rhodium-catalyzed conjugate addition of potassium trifluoro(organo)borates to dehydroalanine derivatives, using chiral ligands such as fluorophos and in situ enantioselective protonation with guaiacol (2-methoxyphenol), afforded a variety of protected α-amino esters with high yields and enantiomeric excesses up to 95%.
L. Navarre, R. Martinez, J.-P. Genet, S. Darses, J. Am. Chem. Soc., 2008, 130, 6159-6169.
Potassium trifluoro(organo)borates, which are highly stable and easily prepared organoboron derivatives, were able to react with various dehydroamino esters to alanine derivatives in good to high yields. This reaction, catalyzed by rhodium complexes, tolerates a great variety of amino protecting groups.
L. Navarre, S. Darses, J.-P. Genet, Eur. J. Org. Chem., 2004, 69-73.
Photoinduced decatungstate-catalyzed Giese reactions of readily available aldehydes as radical precursors with dehydroalanine provide γ-carbonyl α-amino acids. This mild, robust method is compatible with a wide array of functional groups and has a broad substrate scope.
X. Wang, Y. Chen, H. Song, Y. Liu, Q. Wang, Org. Lett., 2021, 23, 2199-2204.
A visible-light-enabled, photocatalyst-free conjugate addition of 4-acyl-1,4-dihydropyridines to dehydroamino acids provides β-acyl α-amino acids and their deuterated analogues in good yields. 4-Acyl-1,4-dihydropyridines serve both as a radical reservoir and reductant. The reaction can be used for late-stage peptide modification and stereoselective synthesis of chiral oxazolidinones.
L. Liu, Z. Deng, K. Xu, P. Jiang, H. Du, J. Tan, Org. Lett., 2021, 23, 5288-5293.