ORGN 25 |
LDA-mediated enolizations: The remarkable accelerating effect of hemilabile ligands
| Antonio Ramirez and David B. Collum. Department of Chemistry and Chemical Biology, Cornell University, 319 Baker Laboratory, Ithaca, NY 14853 |
| Hemilabile amino ethers promote the LDA-mediated enolization of ester 1 with up to a 10,000-fold acceleration relative to n-BuOMe. The observed rates far exceed those measured for enolizations in THF, DMPU, or even HMPA. Thus, the potential importance of hemilabile ligands to facilitate recalcitrant enolizations is substantial. Mechanistic investigations of LDA-mediated enolizations of ester 1 and the much less reactive carboxamide 2 reveal a dimer-based mechanism. The reaction coordinates are explored and modeled using DFT computations. A proof-of-principle demonstration of how such bifunctional ligands can be used catalytically is accompanied by a discussion underlying issues and mechanistic complexities. 
|
| |
|
|