Enantioselective synthesis of (R)- and (S)-alpha-alkylcysteines via phase-transfer catalytic alkylation.

Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
The Journal of Organic Chemistry (Impact Factor: 4.56). 10/2006; 71(21):8276-8. DOI: 10.1021/jo061107t
Source: PubMed

ABSTRACT We reported efficient enantioselective synthetic methodologies for (R)-alpha-alkylcysteines and (S)-alpha-alkylcysteines. The phase-transfer catalytic alkylation of 2-phenyl-2-thiazoline-4-carboxylic acid tert-butyl ester and 2-o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl ester, in the presence of chiral catalysts (1 or 2), gave the corresponding alkylated products, which could be hydrolyzed to provide (R)-alpha-alkylcysteines (67->99% ee) and (S)-alpha-alkylcysteines (66-88% ee), respectively.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Phase-transfer catalysis is one of the most useful methodologies for practical syntheses given its operational simplicity and mild reaction conditions that enable its application in industrial processes. Cinchona alkaloids have been a popular, natural source of practical organocatalysts due largely to their excellent commercial availability and low cost. Since the first Cinchona alkaloid-derived phase-transfer catalysts was disclosed in 1981, diverse generations of Cinchona-derived phase-transfer catalysts have been developed and successfully applied to various asymmetric syntheses. In this feature article, we describe the generation of Cinchona-derived chiral phase-transfer catalysts according to the development stages and our efforts toward the design of polymeric Cinchona phase-transfer catalysts, the effects of the electronic functional group incorporated in the catalysts, and their application in asymmetric organic reactions.
    Chemical Communications 12/2009; · 6.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An efficient enantioselective synthetic method for the synthesis of (2R)-5-phenyl-2-alkylproline tert-butyl esters was reported. The phase-transfer catalytic alkylation of tert-butyl-5-phenyl-3,4-dihydro-2H-pyrrole-2-carboxylate in the presence of chiral quaternary ammonium catalysts gave the corresponding alkylated products (up to 97% ee). The following diastereoselective reductions afforded chiral 5-phenyl-2-alkylprolines which can be applied to asymmetric synthesis as organocatalysts or synthesis of biologically active proline based compounds, such as chiral α-alkylated analogues of (+)-RP66803, as potential CCK antagonists.
    Organic & Biomolecular Chemistry 02/2013; · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phase-transfer catalysis has been recognized as a powerful method for establishing practical protocols for organic synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large-scale synthesis, and the environmentally benign nature of the reaction system. Since the pioneering studies on highly enantioselective alkylations promoted by chiral phase-transfer catalysts, this research field has served as an attractive area for the pursuit of "green" sustainable chemistry. A wide variety of asymmetric transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable organic compounds in the past several decades, especially in recent years.
    Angewandte Chemie International Edition 02/2013; · 11.34 Impact Factor


Available from