DESIGN AND SYNTHESIS OF NEW SULFONATED CNN LIGAND SCAFFOLDS FOR PLATINUM CATALYZED H/D EXCHANGE APPLICATIONS

Abstract

The use of platinum group metals for the activation and functionalization of C-H bonds has been a topic of substantial interest over the past 60 years. Specifically, platinum-based complexes represent a particularly promising avenue due to their ability to form air- and water-stable species that are capable of reacting with some of the most inert C-H bonds within organic substrates. Over the decades of research contributing to this field, platinum complexes have frequently been angled towards fundamental mechanistic analysis of homogeneous C-H bond activation. In turn, the development of homogenous PtII-based catalytic systems has remained underdeveloped for the practical applications in C-H bond functionalization and, in particular, deuteration of complex organic molecules, including pharmaceuticals. The latter direction is now attracting a significant interest by the pharmaceutical industry. In this work the kinetic and thermodynamic selectivity of our new catalyst, a Pt(II) sulfonated CNN-pincer complex 1.5, in the H/D exchange reaction between aromaticsubstrates and wet TFE-d1 was screened across thirty-four aromatic substrates with the catalysts TON up to 300 (Chapter 2). A kinetic preference of 1.5 for electron-rich C-H bonds and substrates was firmly established and a novel scale of Hammett-like σXM constants was introduced to characterize the reactivity of the substrates’ C(sp2)–H bonds in transition-metal-mediated C-H activation. To greatly enhance our PtII catalysts’ useful life, we used their rigid covalent immobilization to mesoporous silica nanoparticles (immobilized complex 3.5). The resulting robust material served as an efficient H/D exchange catalyst utilizing cheaper sources of exchangeable deuterium, AcOD-d4, and D2O, with the catalyst’s TON up to 1600 (Chapter 3). To understand our novel catalyst’s structure – activity relationship, a series of benzene fragment – R-substituted analogs of 1.5 (R = MeO, tBu, iPr, F, Cl, CF3) were synthesized and explored in the H/D exchange of a series of aromatic compounds (Chapter 4). Surprisingly, the complex 4.1-tBu (R = tBu) stood out as a most robust homogeneous catalyst compatible with AcOD-d4 and D2O at 120 oC as deuterium sources that can work under air. Thanks to this finding, the substrates scope for the H/D exchange with AcOD-d4 catalyzed by 4.1-tBu was expanded to include eight pharmaceuticals, some alkenes, with signs of engagement of some C(sp3)-H bond donors. A novel photo-induced (violet light) room temperature H/D exchange catalyzed by 4.1-OMe was discovered with a substantially different substrate selectivity, as compared to the thermal reaction at 80 oC. These observations may provide some important insight into the mechanism of PtII-mediated C-H activation. Finally, Chapter 5 summarizes the results of this work and suggests some future directions for this area of research.