Chiral enolate design
The basic design features associated with the construction of chiral propionate enolates will be presented. It has been found that amide and imide enolates derived from -amino alcohols exhibit excellent levels of asymmetric induction in both alkylations and aldol condensations. For the aldol condensations metal structure was found to be of critical importance in the control of both threo-diastereoselection and chirality transfer. Both boron and zirconium enolates were found to be excellent substrates for the aldol process where >98% enantioselection was observed. INTRODUCTION One of the major objectives in organic synthesis has been the development of general strategies for stereoselective bond construction (1). Nonetheless, the goal of developing carbon-carbon bond construction reactions, wherein chiral molecules are produced in high enantiomeric purity, has been a challenging as well as elusive endeavor. One need only examine the architectural complexity of the macrolide antibiotics and polyether-based ionophores to appreciate the fact that the syntheses of these and related target structures would be greatly simplified if such methodology were in hand. Over the last two years, our laboratory has been attempting to develop classes of chiral carboxylic acid enolate synthons which perform effectively in both enantioselective alkylations and aldol condensations. This lecture will present the chiral enolate design concepts which we have followed during the course of our investigations. General transition state models for predictable chirality transfer will be presented during the course of the discussion.