Synthetic Inorganic and Organometallic Research
We study the chemistry of Mn(III) halide and pseudohalide compounds
Overview: Manganese(III), Nature’s highest-potential one-electron oxidant (1.23 V vs NHE), plays a central role in biological processes such as photosynthesis and carbon cycling. Despite its natural significance, its high-potential properties in synthetic chemistry remain untapped due to the absence of well-defined, accessible Mn(III) reagents. The Lacy group has overcome this limitation by developing bench-stable high-potential (>1.23 V vs NHE) Mn(III) complexes and is now investigating their reactivity to enable new synthetic methodologies with implications across several disciplines. Technical details about our research are provided below.
• Why Mn(III)?
A significant portion of reactions performed by chemists rely on transition metals. While remarkable progress has been made in using 1st-row metals such as Co, Ni, and Cu for sustainable metal chemistry, these elements are neither as abundant in the Earth’s crust nor as benign to human health as Fe, Ti, and Mn, which are the three most abundant transition metals. Despite their abundance, Mn-based reagents remain underdeveloped relative to Fe and Ti, which benefit from a wealth of stable binary precursors (e.g., TiIVX4, TiIIIX3L, FeIIX2, and FeIIIX3; X = halide or pseudohalide). In contrast, the chemistry of Mn is constrained by the limited availability of binary MnX reagents, which consists of comparatively redox-inert Mn(II) salts, “Mn(OAc)3”, and unreactive mineral-like MnF3. The barrier to expansion is the inaccessibility of binary Mn(III) halides and pseudohalides, such as MnCl3, because they are thermodynamically and kinetically unstable. Though the limited set of Mn starting materials has not prevented the advancement of useful reagents like Mn(OAc)3, KMnO4, Mn(III) salen complexes and other designer catalysts, the absence of Mn(III) halides and pseudohalides (MnIIIX3) from the chemists’ toolbox reveals an intriguing question. Are chemists overlooking potentially transformative compounds and reactivity profiles? There is compelling reason to believe the answer is yes. Manganese(III) is Nature’s highest-potential one-electron oxidant (1.23 V vs NHE) and plays critical roles in Earth’s most important biological processes including photosynthesis and closing the carbon cycle. However, chemists do not have access to Mn(III) reagents that possess this high-potential reactivity. Reagents like Mn(OAc)3 and Mn(acac)3 are not high-potential oxidants, MnF3 is mostly unreactive, and porphyrin/salen Mn catalysts require activation to Mn(IV) and (V) oxidation states to access their characteristic reactivities. We reasoned that the intrinsic high potentials of MnIIIX3 compounds is fundamental to their instabilities, and that these instabilities represent unique and tractable reactivities. In order to test this hypothesis, we first had to solve another critical challenge: how to synthesize high-potential MnIIIX3 compounds amenable to such studies. Having overcome this challenge, the we are now seeking federal funding to continue this Mn-focused program and address the significant knowledge gap, which is that chemists have yet to capitalize on the latent high-potential properties of the Mn(III) ion in synthetic chemistry. The significance of this work lies in its foundational nature, uncovering the reactivities of Mn(III) halides and pseudohalides as a new class of high-potential oxidants, and their potential to have translational impact in organic synthesis and bioinorganic chemistry. The innovations of this work stem from the unprecedented access to bench-stable, high-potential Mn(III) oxidants, enabling the development of new hypotheses and mechanistic frameworks that redefine Mn-based reactivity in synthesis.
• Our goals
We have uncovered unique reactivities for [LMnIIIX3] complexes, including undirected thermal C–H bond functionalization, phenol oxidation, alkene dichlorination, and reductive elimination to form new P–X and potentially C–C bonds. Understanding the mechanisms underlying these transformations is essential for advancing manganese chemistry and enabling systematic exploration of their applications. To this end, we are investigating the reaction pathways of these complexes using our expertise in physical inorganic chemistry and synthesis. Advanced techniques such as low-temperature UV-vis, EPR, XAS, and cryo-electron microscopy will be employed to delineate key mechanistic features. Preliminary studies have already uncovered unique reactivity profiles compared to other high-valent metal halogen systems, further justifying the significance of this work.
In addition to fundamental inorganic chemistry, we aim to demonstrate the impact of our discoveries across multiple disciplines. A primary objective is to define the substrate scope and functional group tolerance of undirected C–H functionalization. To achieve this, we have developed a drop-in “pick your X C–H functionalization” strategy using a novel Mn(III) precursor, enabling rapid screening of X-sources, conditions, and substrates. Another key objective is to demonstrate the latent reactivity of Mn(IV) intermediates—generated via Mn(III) disproportionation—in catalytic C–C coupling. These studies also include several collaborations with various faculty from around the globe, including advanced spectroscopy, computational research, and late stage functionalization of bioactive molecules. None of these projects are currently funded by federal agencies and we are currently seeking support to continue this program.
• Unprecedented access to the chemistry of MnCl3
https://doi.org/10.1021/jacs.2c08509
https://doi.org/10.1021/jacs.3c03651
• News articles on discovery…
https://www.chemistryviews.org/bench-stable-manganeseiii-chloride-source/
https://www.nature.com/articles/s44160-022-00181-7#citeas
https://www.buffalo.edu/news/releases/2022/10/001.html
• Demonstration that MnIIIX3 compounds are high-potential compounds
https://doi.org/10.1021/jacs.4c03411
• Phosphine coordinated MnIIIX3 complexes
https://doi.org/10.1021/acs.inorgchem.4c01820
• Ligands tune the reactivity of MnIIIX3 complexes
https://doi.org/10.3390/molecules29194670