Executive Summary : | The researchers propose a new synthetic approach for synthesizing biologically active compound classes using two catalysts in combination. This approach reduces energy and resource demands, promoting a greener approach to molecules in medicine and healthcare. The combination of two catalysts, one nucleophilic and one acidic, offers advantages but presents compatibility challenges. The researchers will create a new class of catalytic asymmetric C1 ammonium enolates as nucleophiles for ring expansion and ring opening chemistry. A chiral organocatalyst and a metal salt will work simultaneously to promote acylammonium ion formation, ring-opening, ring expansion, and [4+2] cycloaddition chemistry. The reactions will demonstrate regio- and stereocontrol, with high yield and enantiopurity. This synergetic catalytic strategy provides a potent synthetic tool for the rapid stereoselective synthesis of small-ring natural products and other bioactive targets. It will also deliver a method for enantioselective annulations to produce ?-lactones and dihydro-quinolinone cores. The researchers aim to demonstrate that selectively producing diverse products from identical substrates is feasible using catalysts rather than substrate control. The design of a dual catalytic system where both Lewis base and metal catalyst work cooperatively remains a formidable challenge but poised to produce great benefits in efficient synthesis. |