Pd/C as a Heterogeneous Catalyst for Ligand-Free Homocoupling Reaction of Halo Compounds in Water and Total Synthesis of Daclatasvir

The United Nations sustainable development goals 9 and 12 discuss about adoption of sustainable and green chemistry concept for manufacturing of pharmaceuticals and chemicals. Water is universally accepted as a green solvent for organic reactions, and solvent-free reactions are considered as green, sustainable methods for synthesis of heterocyclic compounds. Pd/C is a heterogeneous, recyclable catalyst and has been used for several cross-coupling reactions. A ligand-free Pd/C-catalyzed homocoupling reaction of haloarenes in water is reported. The reaction condition is mild (reaction temp. 40 degrees C), and the desired products were isolated in moderate to good yield (56%-81%). Activation of phase transfer catalyst under microwave irradiation reduced the catalyst loading and reaction time (from 24 h to 30 min). The major advantages of this method over existing methods are (i) ligand-free homocoupling reaction, (ii) lower Pd/C catalyst loading, and (iii) use of water as a green and sustainable solvent. This reaction along with continuous-flow bromination, and amine deprotection reactions were successfully applied for synthesis of antiviral drug daclatasvir.