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.