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The Roles of Counterion and Water in a Stereoselective Cysteine‐Catalyzed Rauhut–Currier Reaction: A Challenge for Computational Chemistry
Author(s) -
Osuna Sílvia,
Dermenci Alpay,
Miller Scott J.,
Houk K. N.
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201300745
Subject(s) - chemistry , nucleophile , stereoselectivity , catalysis , counterion , derivative (finance) , cysteine , medicinal chemistry , solvation , organic chemistry , molecule , ion , financial economics , economics , enzyme
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 (1 S , 2 R , 3 S )/(1 R , 2 S , 3 R ).