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Origin of Chemoselectivity in N-Heterocyclic Carbene Catalyzed Cross-Benzoin Reactions: DFT and Experimental Insights

Author:
Langdon, Steven M., Legault, Claude Y., Gravel, Michel
Source:
Journal of organic chemistry 2015 v.80 no.7 pp. 3597-3610
ISSN:
1520-6904
Subject:
aldehydes, carbenes, catalysts, chemical bonding, chemoselectivity, energy, heterocyclic nitrogen compounds, nuclear magnetic resonance spectroscopy, organic chemistry
Abstract:
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 ¹H 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.
Agid:
5505276