Origin of chemoselectivity in N-heterocyclic carbene catalyzed cross-benzoin reactions: DFT and experimental insights.
An exploration into the origin of chemoselectivity in the NHC-catalyzed cross-benzoin reaction reveals several key factors governing the preferred pathway. In the first computational study to explore the cross-benzoin reaction, a piperidinone-derived triazolium catalyst produces kinetically controlled chemoselectivity. This is supported by (1)H NMR studies as well as a series of crossover experiments. Major contributors include the rapid and preferential formation of an NHC adduct with alkyl aldehydes, a rate-limiting carbon-carbon bond formation step benefiting from a stabilizing π-stacking/π-cation interaction, and steric penalties paid by competing pathways. The energy profile for the analogous pyrrolidinone-derived catalyst was found to be remarkably similar, despite experimental data showing that it is less chemoselective. The chemoselectivity could not be improved through kinetic control; however, equilibrating conditions show substantial preference for the same cross-benzoin product kinetically favored by the piperidinone-derived catalyst.
†Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
Steven M
SM
Langdon
‡Département de Chimie, Université de Sherbrooke, 2500 Boulevard Université, Sherbrooke, Quebec J1K 2R1, Canada.
Claude Y
CY
Legault
†Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
Michel
M
Gravel