Optically active aromatic and heteroaromatic alpha-amino acids by a one-pot catalytic enantioselective addition of aromatic and heteroaromatic C-H bonds to alpha-imino esters.
The development of a practical one-pot catalytic enantioselective procedure for the synthesis of non-natural aromatic and heteroaromatic alpha-amino acids is reported. Starting from readily available starting materials and application of a chiral BINAP-Cu(I) catalyst, the optically active products are formed with readily removable N-protecting groups. The scope of the reaction is demonstrated by the addition of substituted furans, thiophenes, pyrroles, and aromatic compounds to N-alkoxycarbonyl-alpha-imino esters in good yields and with enantioselectivities up to 96% ee for the furans, 93% ee for the thiophenes, and 98% for the aromatic compounds. The protecting groups are readily removed, and various transformations of the aromatic and heteroaromatic alpha-amino acids are demonstrated. The coordination of the N-alkoxycarbonyl alpha-imino ester to the chiral BINAP-Cu(I) complex and the enantioselectivity of the catalyst is discussed on the basis of the DFT calculations and X-ray crystallographic data.
Saaby
Steen
S
Center for Catalysis, Department of Chemistry, Aarhus University, Denmark.
Bayón
Pau
P
Aburel
Pompiliu S
PS
Jørgensen
Karl Anker
KA
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism; D013876:Thiophenes / Q000737:chemistry
D000596:Amino Acids; D004952:Esters; D005663:Furans; D011758:Pyrroles; D013876:Thiophenes