Ligand-free Pd/C-catalysed and microwave-assisted activation of phase transfer catalysts for sustainable synthesis of biaryl compounds and antiviral drug daclatasvir in water

The United Nations sustainable development goals 9 and 12 discuss about adoption of sustainable and green chemistry concept for manufacturing of chemicals. Water is universally accepted as a green solvent and solvent-free reactions are considered as green, sustainable chemistry. Pd/C is a heterogenous, recyclable catalyst used for cross coupling reactions. A ligand-free Pd/C-catalyzed homocoupling of haloarenes in water is reported. The reaction condition is mild, and the desired products yields are 56%-81%. Activation of phase transfer catalyst under microwave irradiation reduced the catalyst loading and reaction time from 24h to 30 min. The key differentiation from existing methods is the ligand-free homocoupling reaction using Pd/C in water with lower catalyst loading, and activation of a phase transfer catalyst under microwave irradiation. This reaction along with continuous-flow bromination, and amine deprotection reactions were successfully applied for synthesis of antiviral drug daclatasvir.