Sustainable Approach Towards the Functionalization of Carbonyl Derivatives: Alkylation, Rearrangement and Lactonization

Abstract

Sustainable chemical synthesis have gained much attention in 20th century. Catalytic reactions to construct the complex organic molecules and drugs with the high selectivity, eliminate the byproduct, avoid the multistep synthesis, use of renewable feedstock and improved process safety were significantly contributed to the sustainable chemistry. Likewise, rearrangement reactions are also much focused for the synthesis of drugs and natural products due to sustainability. Moreover, integration of continuous flow technologies with the catalysis have several advantages with augmented safety in the large scale reactions. Currently, synthetic community much focused on the integration of flow chemistry for the synthesis of organic intermediates, drugs and other applied materials. To this direction, we have investigated the sustainable alkylation using alcohols and 1,3-dicarbonyl compounds to construct C-C and C-O bond for the chemoselective synthesis of C-alkylated and O-alkylated carbonyl derivatives under batch condition. This reaction were also successfully transformed into the continuous flow for the safer and rapid reactions to afford multigram product. The developed method has been successfully employed for the synthesis of the commercially available ondansetron drug. Next, we have studied the selective methylallylation of C3-hydroxy oxindole and C3-peroxyoxindole derivatives using the tert-butyl acetate as a source of olefin in the presence of In or Ni as a catalyst. However, chemodivergent reaction was observed when conjugated ester reacted with the tert-butyl acetate to form the lactone in the presence of In-catalyst under batch/flow condition. The reactivity and stability of the peroxyoxindole were investigated with the various metal catalyst and a novel rearrangement has been discovered when peroxyoxindole was treated with catalytic Fe(II)- catalyst. All the above studies were investigated with the several substrates and the appropriate mechanism was justified by the detailed experimentation.