Synthesis of Quaternary-Carbon-Containing β 2,2 -Amino Acids by the Rh I -Catalyzed Enantioselective Arylation of α-Substituted β-Nitroacrylates.

An enantioselective Rh-I-catalyzed conjugate addition reaction of alpha-substituted beta-nitroacrylates with various arylboronic acids by using chiral Rh-I diene catalysts is described for the first time. The addition reaction proceeds under mild conditions in a range of common organic solvents and additives, and it affords the corresponding quaternary-carbon-containing alpha,alpha-disubstituted beta-nitropropionate products in up to 63% yield and 99% ee. Reaction of either (E)- or ( Z)- beta-nitroacrylates provided the same enantiomer of the product, and a range of esters and aryl groups were tolerated. To demonstrate the utility of the method, ethyl (R)1,1-methyl-1-phenyl-3-nitropropionate, prepared herein, was converted to the non-proteinogenic beta(2,2)-amino acid, (R)-2(aminomethyl)-2-phenylpropanoic acid, and to the beta(2,2)lactam, (R)-3-methyl-3-phenylazetidin-2-one. In addition, a tripeptide, which comprised L-phenylalanine, L-alanine, and beta(2,2)-amino acid 7, was also synthesized.