Preparation and Use of Polystyryl-DABCOF2: An Efficient Recoverable and Reusable Catalyst for β-Azidation of α,β-Unsaturated Ketones in Water

Novel solid fluorides were prepared to optimize the beta-azidation of a,beta-unsaturated ketones. The higher loading of these catalysts compared to that of commercially available fluorides has allowed the use of a smaller mass of catalyst helping the mixing of the reaction mixture. Porous polymeric supports have proved to be more efficient in the presence of water as reaction medium. Water has played a crucial role showing a beneficial effect on the reactivity by improving dispersion of the reaction mixture and also by avoiding organic fouling caused by the retention of the reaction mixture within the polymeric matrix. This has facilitated the recovery of the products from the catalyst. The protocol reported has allowed a significant reduction in the organic solvent required for the complete recovery of the pure product whilst leaving the catalyst clean and reusable. E-factors are in the range of 5.910.5 and therefore ca. 3 times smaller than previous procedures operating under solvent-free conditions. To further improve the efficiency of our approach we have developed a protocol operating in a continuous-flow manner that has allowed us to achieve an E-factor of 1.71.9, with a reduction of ca. 80% of the corresponding batch conditions. The continuous-flow protocol has allowed us to minimize the use of trimethylsilyl azide making the recovery and reuse of water and catalyst 5f very efficient and simple. Finally, a novel reduction system using palladium on alumina (5 mol%) and equimolar amount of formic acid has been used in the presence of 1 equivalent of di-tert-butyl pyrocarbonate to set a multistep protocol operating in continuous-flow conditions for the preparation of two representative N-Boc-beta-amino ketones starting from the corresponding enones with E-factors of 3.2 and 2.7, respectively.