Asymmetric 1,4-addition of oxazolones to nitroalkenes by bifunctional cinchona alkaloid thiourea organocatalysts: synthesis of alpha,alpha-disubstituted alpha-amino acids.
An easy and simple synthetic approach to optically active alpha,alpha-quaternary alpha-amino acids using asymmetric organocatalysis is presented. The addition of oxazolones to nitroalkenes catalyzed by thiourea cinchona derivatives provides the corresponding alpha,alpha-quaternary alpha-amino acid derivatives with good yields, excellent diastereoselectivities (up to 98 % dr), and from moderate to good enantioselectivities (up to 92 % ee). The reaction can be performed on a large scale. The optically active oxazolone-nitroalkene addition products can be opened in a one-pot reaction to the corresponding ester-amide derivatives. Additional transformations are also presented, such as the synthesis of amino esters, amino acids, and transformation into 3,4-disubstituted pyrrolidin-2-ones.
Alemán
José
J
Danish National Research Foundation Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
Milelli
Andrea
A
Cabrera
Silvia
S
Reyes
Efraim
E
Jørgensen
Karl Anker
KA
D000475:Alkenes / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry; D009574:Nitro Compounds / Q000737:chemistry; D010081:Oxazolone / Q000737:chemistry*; D013890:Thiourea / Q000737:chemistry
D000475:Alkenes; D000596:Amino Acids; D002930:Cinchona Alkaloids; D009574:Nitro Compounds; D010081:Oxazolone; D013890:Thiourea