Research Projects

We propose to develop cutting-edge approaches for enantioselective alkynylation and propargylation. Our focus is on harnessing chiral Lewis base catalysts in conjunction with electrophilic alkynyl and propargyl reagents to develop a new synthetic method for enantiopure intermediate synthesis to achieve the important enantiopure pharmaceutical and agrochemical molecule. Catalytic methods for synthesizing reagents offer significant advantages by lowering the energy and resource requirements. Our research aims to support a more sustainable development of valuable molecules for medicine and healthcare. The use of a nucleophilic catalyst alongside an acidic one offers distinct benefits, although it also brings challenges related to their compatibility that we aim to address. Earlier, A. D. Smith and T. Snaddon's teams have demonstrated that tertiary amine catalysis via C(1)-ammonium enolate intermediates offers a powerful approach to synthesizing complex molecules featuring α-functionalized carboxylic acids, amino acids, amino esters, carboxylic esters and amides. This methodology leverages mild basic conditions to achieve high enantiopurity and functional group compatibility. We are excited to introduce an exciting expansion of chiral tertiary amine Lewis base catalysis with a much wider range of substrates. This will facilitate the synthesis of enantioenriched α-alkynylated and propargylated intermediates by chiral isothiourea Lewis base with metal catalysis or without metal catalyst. A chiral Lewis base catalyst activates the aryl acetic acid ester by forming a C1-ammonium enolate. This enolate then attacks the activated electrophile, introducing a new functional group at the α-position of the substrate. This step is crucial in the synthesis of key intermediates for pharmaceutical and agrochemical molecules. The reactions will exhibit regio- and stereocontrol and will aim for high yield and enantiopurity. This chiral Lewis base catalytic strategy, the use of a chiral isothiourea Lewis base catalyst, provides a potent synthetic tool for the rapid stereoselective synthesis of small-ring natural products and other bioactive targets. For the first time, it will deliver a method for enantioselective alkynylation and propargylation reaction to produce γ-lactone, butanolide, dihydrofuran, and 3,4 dihydro-α-Pyrone cores. It’s still a challenge to selectively create a variety of products from the same substrates. However, we aim to demonstrate that this can be achieved by using catalysts instead of controlling the substrates. The project is expected to generate results of significance beyond the narrower field of organic chemistry, and our publishing strategy will aim for at least four to five high-impact papers.