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 DFT (M06-2X) theory. 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 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 8 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).

A DFT study on Diels-Alder cycloadditions oftrans-1,3-butadiene to C60and C70

“…The hybrid meta exchange‐correlation functional M06‐2X performed well in the thermochemistry as well as the kinetics and non‐covalent interactions of systems involving main‐group atoms . The computational studies proved that M06‐2X was reliable for different kinds of cycloaddition reactions when used at a suitable basis set . Recently, M06‐2X functional was employed for exploring the DA cycloaddition of cyclopentadiene to La@ C 82 , whose results were well consistent with the experimental observations …”

The Chemical Record Lectureship: S. J. Miller / Nagoya Gold Medal: J. F. Hartwig / Nagoya Silver Medal: I. Hamachi / Kyoto Prize: R. S. Langer

“…Miller’s research interests are in the selective synthesis of complex molecules, in particular the development of new catalysts and the catalytic modification of natural products. He has reported in Angewandte Chemie on the catalytic site‐selective deoxygenation of hydroxy groups,1a and in Chemistry—A European Journal on the cysteine‐catalyzed Rauhut–Currier reaction 1b…”

The‐Chemical‐Record‐Vortrag: S. J. Miller / Nagoya‐Goldmedaille: J. F. Hartwig / Nagoya‐Silbermedaille: I. Hamachi / Kyoto‐Preis: R. S. Langer

“…Sein Forschungsinteresse gilt der selektiven Synthese komplexer Moleküle, vor allem der Entwicklung neuer Katalysatoren und der katalytischen Modifizierung von Naturstoffen. In der Angewandten Chemie hat er die katalytische ortsselektive Desoxygenierung von Hydroxygruppen vorgestellt1a und in Chemistry—A European Journal die cysteinkatalysierte Rauhut‐Currier‐Reaktion 1b…”