Micellar catalysis for eco-friendly hydroaminomethylation (HAM)

Hydroaminomethylation (HAM) is one of the most interesting atom economic metal catalysed process for the production of amines. Despite the large application of HAM in the synthesis of aliphatic amines, anilines, interesting intermediates in APIs synthesis, are still challenging substrates for this reaction. Herein it is reported the development of a protocol that combines micellar catalysis and microwave heating for the eco-friendly HAM of anilines by using water as the reaction medium. Secondary and tertiary anilines are obtained in good yields and regioselectivity with a full recovery of the catalyst in the water/micellar media that can be reused several times without drastic impacts on the reaction yields and regioselcetivity. The final amines are obtained as pure products by filtration on SCX columns. The characterization of the possible active catalytic species involved in the process is also reported. Mechanistic investigations suggest a different pathway compared to the commonly observed mechanism with homogeneous catalysts for the reported HAM reaction. Finally, LCA analysis of the protocol was performed, that demontrates the greeness and low environmental impact of the process. Beside this work, the synthesis of a small library of potential inhibitors of SIRT1, deacetylase involved in noumerous biological pathways and pathologies, included anxiety and depression, is reported. Finally, a third section is dedicated to design and early stage synthesis of a photolabeling probe precursor, by functionalization of quinoline compounds endowed with a good antibacterial activity, for the future further investigation of the interactions between these compounds and bacteria.