Rate of enolate formation is not very sensitive to the hydrogen bonding ability of donors to carboxyl oxygen lone pair acceptors; a ramification of the principle of non-perfect synchronization for general-base-catalyzed enolate formation.
Two series of structures (1 and 2) possessing intramolecular hydrogen bonds to the lone-pair electrons of carbonyl oxygens have been examined to reveal the influence of the pK(a) of the hydrogen-bond donor on the rate of general-base-catalyzed enolate formation. The geometry of the hydrogen bonds is well accepted to be appropriate for intramolecular hydrogen-bond formation. Yet, as revealed by Brønsted plots, both series show very little dependence of the rate of enolate formation on the hydrogen-bond donor ability. The intramolecular hydrogen bonds give rate enhancements only on the order of 10-100-fold, and corrected Brønsted alpha-values are slightly below 0.1. The results can be understood by interpreting them in light of the Principle of Non-Perfect Synchronization. The results are consistent with the proton transfer occurring through an asynchronous transition state with the developing negative charge localized on carbon. We postulate that catalysts of enolate formation will be most effective if the binding groups are focused on stabilizing negative charge that is forming on the enolate carbon rather than on the enolate oxygen.
Zhong
Zhenlin
Z
Department of Chemistry and Biochemistry, 1 University Station, A5300, The University of Texas at Austin, Austin, Texas 78712, USA.
Snowden
Timothy S
TS
Best
Michael D
MD
Anslyn
Eric V
EV
D000438:Alcohols / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D041961:Deuterium Exchange Measurement; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics
D000438:Alcohols; D000588:Amines; D007659:Ketones