Recent Studies on the Regioselective C-Protonation of Enol Derivatives using Carbonyl-Containing Proton Donors

Abstract

Both enantio-1 and diastereoselective 2 C-protonation of achiral and chiral enolates is well known. Many of these reports deal with proton transfer under kinetic control, 3 whereas protonation under thermodynamic control has become more popular when diastereoselective control is required. 4 There are only a few cases where the stereochemistrydetermining protonation step is under reagent control, 5 the most notable examples being the use of chelating proton donors (CPDs) such as salicylic esters 1, 6 and β-amino alcohols 2 (Scheme 1). 7 The salient feature of these chelating acids such as 4 is their ability to chelate to the metal cation of an enolate such as 3 and aid protonation directly onto carbon 8 of the corresponding enolate 6 (to give the carbonyl derivative 7), rather than in some cases the preferred protonation on oxygen (to give the enol 5), 9 tautomerisation of which would lead to the thermodynamically preferred carbonyl derivative 7. 10 2 J. CHEM. RESEARCH (S), 2001 * To receive any correspondence.

The Synthesis and Structure of Substituted Dimenthyl Malonate Derivatives

“…We previously investigated the use of 1,3-dicarbonyl containing molecules as achiral proton donor in the enantio- [12] and regioselective protonation [13] of prostereogenic enolates. However, reports into the preferred conformation of these chiral carbon-based acids are limited [14].…”