Mechanism And Scope For N-Heterocyclic Carbene Mediated Cross-Coupling Of Aromatic Aldehydes With Activated Halides

N-Heterocyclic Carbene(NHCs) is the most common and important organocatalyst in umpolung reaction. Among various kinds of reactions catalyzed by NHCs, Stetter reaction attracted a great deal of attention by playing an outstanding role in asymmetric catalysis and synthesis of natural products and drug intermediates, but the electrophilic reagents are limited toα,β-unsaturated carbonyl compounds as Michael acceptor. The research on N-Heterocyclic Carbene mediated nucleophilic substitution reaction is less common compared to others. Currently, according to the published reports, the substrates of nucleophilic substitution reaction were lack of diversity, or the reaction only proceeded intramolecularly, or the mechanism of reaction was the same as Stetter reaction. In the nucleophilic substitution reaction we studied, halogenated hydrocarbons were chosen as electrophilic reagents instead of Michael acceptor. The reaction of aromatic aldehydes and halogenated hydrocarbons mediated by NHCs generated various kinds of bioactive molecules or their intermediates containing building block ethnone, which not only widened the scope of nucleophilic subsititution reaction, but also can be applied to synthesize important intermediat of medicine, essence and perfume. After optimization of reaction conditions including catalysts, reaction temperature, solvents etc., we finally established the optimal reaction system. In addition, we also explored the mechanism of this reaction to seek guidance for further optimization.