Synthesis of Quaternary-Carbon-Containing β2,2 -Amino Acids by the RhI -Catalyzed Enantioselective Arylation of α-Substituted β-Nitroacrylates.

Abstract

An enantioselective RhI -catalyzed conjugate addition reaction of α-substituted β-nitroacrylates with various arylboronic acids by using chiral RhI 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 α,α-disubstituted β-nitropropionate products in up to 63 % yield and 99 % ee. Reaction of either (E)- or (Z)-β-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 β2,2 -amino acid, (R)-2-(aminomethyl)-2-phenylpropanoic acid, and to the β2,2 -lactam, (R)-3-methyl-3-phenylazetidin-2-one. In addition, a tripeptide, which comprised l-phenylalanine, l-alanine, and β2,2 -amino acid 7, was also synthesized.