3.2 Roles of NHC
As an organocatalyst, the NHC species work generally to enhance
electrophilicity of the substrate, to manipulate stereoselectivities by
rational regulations of the non-covalent interactions between
substituents of the chiral catalyst and the substrate, or most
importantly to inverse polarity of the ketene, ketone, or aldehyde to
expand applications of NHCs in synthesis of heterocyclic compounds. In
regarding the title reaction we are interested in, the experimental
results from Biju and co-workers indicate that the yield can be
dramatically decreased to be 7% when all reagents were set under
exactly the same conditions but with NHC absent and the phenyl
substituted aldimine replaced by benzyl substituted aldimine. Moreover,
according to all the above discussions about the catalytic cycle, it is
easy to conclude that the reaction undergoes without polarity reversal.
So what kind of roles do the NHC catalyst act in this transformation
from o-amino phenol to benzoxazole? Why it is so important for promoting
the transformation going efficiently?
In order to get some insights into these queries, we then conducted
mechanism studies to the reaction without participation of NHC. As
illustrated in Figure 2(a), the whole reaction was proposed to occur
through four steps, namely deprotonation of the phenolic hydroxy group
in Rnc to give ionic compoundInt1nc , followed by a conformation isomerism of
the aldimine group to give Int2nc .
Subsequently, two possible transformation pathways were considered, i.e.
ring closure through nucleophilic attack of the O4 atom to the C2 atom
followed by oxidation by DQ , or the oxidation of the C2 atom
goes first, followed by ring closure through bonding of the C2 and O4
atoms. The predicted Gibbs free energy profiles of the whole reaction
were presented in Figure 2(b), and the energies ofRnc + KOt -Bu was set as the reference of
0.0 kcal/mol unless otherwise specified.