title: The roles of counterion and water in a stereoselective cysteine-catalyzed Rauhut-Currier reaction: a challenge for computational chemistry.
abstract: The stereoselective Rauhut-Currier (RC) reaction catalyzed by a cysteine derivative has been explored computationally with density functional theory (M06-2X). Both methanethiol and a chiral cysteine derivative were studied as nucleophiles. The complete reaction pathway involves rate-determining elimination of the thiol catalyst from the Michael addition product. The stereoselective Rauhut-Currier reaction, catalyzed by a cysteine derivative as a nucleophile, has also been studied in detail. This reaction was experimentally found to be extremely sensitive to the reaction conditions, such as the number of water equivalents and the effect of potassium counterion. The E1cB process for catalyst elimination has been explored computationally for the eight possible stereoisomers. The effect of explicit water solvation and the presence of counterion (either K(+) or Na(+) ) has been studied for the lowest energy enantiomer pair (1S, 2R, 3S)/(1R, 2S, 3R).
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA). sosuna@chem.ucla.edu.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Osuna
authors.forename: Alpay
authors.initials: A
authors.lastname: Dermenci
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
authors.forename: K N
authors.initials: KN
authors.lastname: Houk
mesh_terms: D002384:Catalysis; D003545:Cysteine / Q000737:chemistry*; D007477:Ions / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011188:Potassium / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry*; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; D014867:Water; D012964:Sodium; D003545:Cysteine; D011188:Potassium
keywords: Rauhut-Currier reaction; density functional calculations; reaction mechanisms; stereoselectivity
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