Preparation of Cu cluster catalysts by simultaneous cooling–microwave heating: application in radical cascade annulation

One of the hallmarks of microwave irradiation is its selective heating mechanism. In the past 30 years, alternative designs of chemical reactors have been introduced, where the microwave (MW) absorber occupies a limited reactor volume but the surrounding environment is MW transparent. This advantage results in a different heating profile or even the possibility to quickly cool down the system. Simultaneous cooling–microwave heating has been largely adopted for organic chemical transformations. However, to the best of our knowledge there are no reports of its application in the field of nanocluster synthesis. In this work, we propose an innovative one-pot procedure for the synthesis of Cu nanoclusters. The cluster nucleation was selectively MW-activated inside the pores of a highly ordered mesoporous substrate. Once the nucleation event occurred, the crystallization reaction was instantaneously quenched, precluding the growth events and favoring the production of Cu clusters with a homogenous size distribution. Herein, we demonstrated that Cu nanoclusters could be successfully adopted for radical cascade annulations of N-alkoxybenzamides, resulting in various tricyclic and tetracyclic isoquinolones, which are widely present in lots of natural products and bioactive compounds. Compared to reported homogeneous methods, supported Cu nanoclusters provide a better platform for a green, sustainable and efficient heterogeneous approach for the synthesis of tricyclic and tetracyclic isoquinolones, avoiding a variety of toxic waste/byproducts and metal contamination in the final products.