IISER MOHALI

Abstract: Macrocycles are widespread structural motifs present in natural products, pharmaceuticals, material science compositions, and have profound importance in supramolecular chemistry. Among these, 1,3-butadiynes or di-acetylenic scaffolds occur widely and to date, over one thousand naturally occurring polynes were isolated and were found to display antibacterial, anti-cancer, anti-HIV, antifungal properties. Metal mediated oxidative dimerization of terminal alkynes with stoichiometric amount of copper was developed by Glaser6 about 160 years ago. Modified reactions such as Glaser-Hay and Cadiot-Chodkiewicz coupling reactions were developed later to prepare unsymmetrical conjugated diynes. Cadiot-Chodkiewicz coupling, though powerful, often suffers from poor selectivity and formation of homo-coupled byproducts. To specifically address the problems related to optimizing chemoselectivity in homo-coupling of alkynes, either of the terminal alkynes should be immobilized on a solid support or should be converted to a haloalkyne under high dilution conditions. Less is known about the Glaser-Hay coupling for macrolactonization, although recent studies by Collins et al. disclosed a novel strategy employing copper catalysis and high concentrations for the synthesis of macrocycles using a “phase separation strategy”. In this lecture, I will discuss the use of gold-copper synergistic catalyst system to effect direct macrocyclization. So far very few examples are reported to achieve intermolecular Glaser-Hay coupling reactions with gold complexes. Moreover, to date, gold-catalyzed intramolecular Glaser-Hay coupling was not utilized to synthesize diyne containing macrolactones.

Tea/Coffee: 11:50 AM