Kinetics and Isotope Effects of the Aldol−Tishchenko Reaction between Lithium Enolates and Aldehydes

1998-04-04T00:00:00Z (GMT) by Faraj Abu-Hasanayn Andrew Streitwieser
The lithium enolate of isobutyrophenone reacts with two molecules of benzaldehyde at room temperature in THF to yield after protonation a 1,3-diol monoester. The kinetics of this process was studied for the reaction of the lithium enolate of <i>p</i>-(phenylsulfonyl)isobutyrophenone (LiSIBP) and benzaldehyde in THF by monitoring the disappearance of LiSIBP. The observed rates obey the rate law −d[{LiSIBP}]/d<i>t</i> = <i>k</i><sub>ob</sub>[{LiSIBP}]<sup>0.83</sup>[benzaldehyde]<sup>2.0</sup> (braces denote initial formal concentration of LiSIBP) and exhibit a kinetic isotope effect <i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 2.0 (determined from independent experiments using benzaldehyde-<i>d</i>). These results and competitive isotope effect experiments are consistent with formation of an initial lithium aldolate (P1), followed by reaction with a second aldehyde to form a ketal (P2), and finally a rate-limiting intramolecular hydride transfer (Tishchenko reaction). These reactions are modeled with <i>ab initio</i> molecular orbital calculations. Corresponding theoretical kinetic and equilibrium isotope effects match the experimentally observed isotope effects and support the proposed reaction scheme.