Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (13): 1464-1470.DOI: 10.6023/A12030050 Previous Articles     Next Articles



刘龑, 王正, 丁奎岭   

  1. 中国科学院上海有机化学研究所 金属有机化学国家重点实验室 上海 200032
  • 投稿日期:2012-03-23 发布日期:2012-05-03
  • 通讯作者: 丁奎岭
  • 基金资助:

    项目受国家自然科学基金(Nos. 21172237, 21121062, 21032007)和“973计划”(No. 2010CB833300)资助.

DpenPhos/Rh(I) Catalyzed Asymmetric Hydrogenation of Dehydro-β-Amino Acid Esters

Liu Yan, Wang Zheng, Ding Kuiling   

  1. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2012-03-23 Published:2012-05-03
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21172237, 21121062, 21032007) and Major Basic Research Program of China (No. 2010CB833300).

Enantiomerically pure β-amino acids and their derivatives are very important chiral building blocks for the synthesis of β-peptides, β-lactams, and many important biologically active compounds. Among various methods developed for their synthesis, catalytic asymmetric hydrogenation of the corresponding dehydro-β-amino acid esters represents one of the most efficient and environmentally benign approaches, in which the Rh(I) catalysts containing chiral phosphorous ligands play a central role. Although a variety of Rh(I) complexes of bidentate or monodentate ligands have been discovered for asymmetric hydrogenation of dehydro-β-amino acid esters, some challenging issues still remain in terms of efficiency, enantioselectivity, and substrate scope. In the present work, a variety of Rh(I) complexes of modular monodentate phosphoramidite ligands, DpenPhos, have been systematically investigated for the asymmetric hydrogenation of (E)- or (Z)-β-substituted dehydro-β-amino acid esters. It was found that the presence of a N-H moiety in the phosphoramidite ligand is critically important for achieving high activity of the catalysis. Both (Z)- and (E)-geometrical isomers of the β-acetamido acrylic acid esters can be hydrogenated in the presence of DpenPhos/Rh(I) catalysts to form the same enantiomers, albeit slightly different conditions were required to attain optimal enantioselectivities. (R,R)-3k/Rh(I) (1 mol%) was disclosed to be optimal for the hydrogenation of (E)-β-alkyl substituted dehydro-β-amino acid esters in dichloromethane under a relatively low pressure of hydrogen (0.5 MPa), affording the corresponding β-amino acid esters with 92%-96% ee. The reaction still proceeded smoothly without significant sacrifice of activity or enantioselectivity either at a catalyst loading of 0.2 mol% or 0.1 MPa pressure of H2. For the hydrogenation of more challenging (Z)-β-alkyl or aryl substituted dehydro-β-amino acid esters, (R,R)-3l/Rh(I) in combination with the dichloromethane/isopropanol (V/V=2/1) mixed solvent system turned out to be the best in terms of enantioselectivity and catalytic activity, giving a variety of β-alkyl or aryl substituted β-amino acid esters in >99% yields with excellent optical purities (92%-98% ee).

Key words: asymmetric catalysis, hydrogenation, monodentate ligand, phosphoramidite, rhodium, dehydro-β-amino acid ester