Exploring New Ligand Space for Small Molecule Activation and Asymmetric Catalysis with Transition Metals
Catalysis plays a pivotal role in modern organic synthesis. In the last few decades, noble metals like Ru, Rh, Pd, and Ir have extensively been utilized in important organic transformations. However, because of their limited availability, high cost, and their negative environmental footprit, recent efforts have shifted to replace these noble metals with more abundant, less toxic, and cheaper first row transition metals. Unfortunately, utilizing these metals for effective catalysis is not trivial due to fundamental differences between the chemistry of first-row and second/third-row transition metals. In particular, for manganese, catalysis can be hampered by unfavorable spin-states (e.g., high-spin Mn(II) d5) that diminsh the reactivity of the metal center. As a result, many methodologies have been developed to overcome some of the limitations through bespoke ligand design. In particular metal-ligand cooperativity has utilized to overcome the unfavorable one-electron chemistry.
Our group’s approach, however, is centered around using strong field ligands in order to access the low-spin manifold allows us to mimic the chemistry of noble metals with ordinary 3d-transition metals. In this seminar I will discuss how we used a Mn(I) pincer complex, with a novel strong field PCNHCP pincer ligand, to functionalize a variety of electronically and sterically differentiated α,ß-unsaturated ketones. In particular, we were able to access value added chemicals through (i) the chemoselective hydrogenation of C=C double bonds using H2 and Mn(I),[1] (ii) through reductive α-methylation methodologies with methanol as both hydrogen and C1-source, and finally (iii) through selective Michael addition of unactivated aliphatic nitriles to α,ß-unsaturated ketones. All three protocols exhibit a large substrate scope and are compatible with a variety of functional groups. Detailed mechanistic studies were performed to elucidate the reaction mechanisms, which includes deuterium labeling studies and the isolation of reactive intermediates.
In the final part of my seminar, I will also show how we used the concept of bespoke ligand design to enable the synthesis of chiral N-heterocyclic carbene (NHC) based ligands. Coordination of these ligands to both first- and second-row transition metals resulted in the formation of a library of metal complexes containing two chiral auxiliaries in their ligand backbone. From among these complexes, the corresponding rhodium complexes showed promising reactivity in the enantioselective Markovnikov hydroboration of styrenes.[2]
References:
[1] K. Dey, G. de Ruiter, Organic Letters 2024, 26, 4173-4177.
[2] K. Dey, Z. Chen, N. Fridman, G. de Ruiter, Organometallics 2024, 43, 817-828.