CHEMISTRY OF ALDOLATE DIANIONS - EFFECTS OF BETA-HETEROATOM SUBSTITUENTS ON KETONE ENOLIZATION

β-Hydroxy ketones can be doubly deprotonated with > 2 equiv of an amide base at low temperature providing both proximal or distal aldolate dianions in good to excellent yield. A variety of substitutionally biased β-hydroxy ketones give exclusively distal dianions. If the distal site is blocked, proximal dianions are formed in good yield; however, chromatographic separation of the silylated products leads to decreased yields. Comparative enolization studies of 4-hydroxy-2-butanone, 1 -hydroxy-3-pentanone, and hydroxyl-substituted derivatives reveal a kinetic factor favoring proximal deprotonation of β-OTMS and β-alkoxy ketones. However, there is a thermodynamic factor favoring distal dianions that becomes significant as solutions of the dianions are warmed. Thermal stability studies indicate good room temperature stability of the dianions toward elimination and retroaldolization processes; control studies in this area also support the presence of a dianionic species. Precedent suggests that the dianions exist as internally chelated species, and we speculate that ion triplets containing bridging lithiums are good candidates for the structure of both proximal and distal dianion species. The distal dianions undergo clean reaction with aldehydes and acyl cyanides leading to β,β'-dihydroxy ketones and β-hydroxy-β'-oxo ketones, respectively. © 1990, American Chemical Society. All rights reserved.