The use of camphor-derived chiral auxiliaries was pioneered by Oppolzer and coworkers in the early 1980s. Offering wide-ranging reactivity with remarkably high selectivities across the board, Oppolzer’s camphorsultam auxiliary became a staple of asymmetric synthesis. Herein, we uncover a myriad of solvent-dependent structures of lithium Oppolzer enolates through NMR, X-ray crystallographic, and computational studies, ranging from tetramers to spirocyclic and symmetric dimers to open and chelated monomers. Unexpectedly, extensive NMR studies revealed a curious bifurcation wherein alkyl-substituted enolates (e.g., propionates and cinnamates) and aryl-substituted enolates (phenylacetates) diverge in structure. Under prototypical alkylation conditions, the Oppolzer enolates are bis-HMPA solvated monomers. Our rate studies focused on alkylation of phenylacetates, an underexplored route to the ubiquitous arylpropionate motif. <i>In situ</i> IR reaction monitoring exposed peculiarly additive cosolvent effects from both toluene and THF, reminding us that seemingly simple reactions are typically anything but. Kinetics studies revealed an ion-pair based mechanism of alkylation, suggesting any ionizing solvent could serve as a benign surrogate for the infamously toxic HMPA.

Structure and mechanism of alkylation of Oppolzer’s camphorsultam-derived enolates

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.