Research

In-Situ Ambient Ionization Mass Spectrometry for Mechanistic Studies of Organometallic Catalysis

Katherine Walker

High-resolution electrospray ionization mass spectrometry (ESI-MS) is an powerful technique for identifying organometallic intermediates in catalytic reactions.1-3 While identifying intermediates is not sufficient for fully understanding a mechanism, it provides one important piece of information that can be combined with traditional kinetic and isotope labeling studies to provide insights on catalytic mechanisms. Additionally, in-situ techniques such as pressurized sample infusion (PSI, Figure 1) can be used to continuously monitor the speciation of organometallic complexes.4 Comparing a compound’s speciation over time (by MS) to the consumption of starting material and formation of products (by NMR or other offline techniques) provides powerful information about that compound’s role in the catalytic cycle. Much of this research is highly collaborative with existing collaborations between the Waymouth Lab and Du Bois Lab (Stanford), and the Muldoon Lab (Queen’s University, Belfast).

A schematic diagram illustrating a laboratory setup for a chemical reaction with fluid flow.Left Section: Displays a syringe connected to a purple tubing, labeled with a flow rate of 300 µL/min. Middle Section: Shows a red reaction solution contained in a flask, with an inlet tube labeled "100 µm ID," indicating a connection to the flow system. Above, there is a nitrogen (N₂) pressure indicator set at 2.2 psi. Right Section: Shows another flask labeled "Waste" connected through more purple tubing with a "250 µm ID." An N₂ pressure indicator here reads 100 psi. A label notes "No applied voltage," indicating that no electrical current is being used in this part of the setup. The diagram captures the specifics of the apparatus for controlling flow and pressure in a chemical reaction process.

Figure 1: Example setup for pressurized sample infusion

The Pd complex [(PBO)Pd][OTf]2 is a selective cationic catalyst for the oxidation of styrene and styrene derivatives to their corresponding ketones using H2O2 as the terminal oxidant.5 Using ESI-MS, two key species: LPdOOH+, and LPdCH2COPh+ were discerned (Figure 2).6 Then, through a series of kinetic and isotope labeling studies, it was shown that the unexpected latter species was indeed an on-path intermediate. Furthermore, this “palladium enolate” has been implicated as an off-path species in other common palladium-catalyzed alkene oxidations with peroxides, such as Sigman’s “Quinox” and tbutyl hydroperoxide system.7 A final Pd alkylhydroperoxide intermediate (LPdCH2C(OOH)Ph) was identified when an H-atom donor was added (Figure 2).

A diagram presenting a chemical reaction and its analysis method.Top Section: Displays the reaction of styrene (C₈H₈) with a palladium complex (indicated with "Pd" and "MeCN·NCMe") in the presence of hydrogen peroxide (H₂O₂) for 24 hours at 27°C, using acetonitrile as a solvent. The products are shown as phenyl acetic acid-like molecules. Middle Section: Illustrates a nitrogen gas (N₂) flow setup with a voltage (V) applied, possibly indicating a mass spectrometry ion source. Bottom Section: Contains representations of ions, labeled with positive charges, and molecules involving palladium and hydroxyl (Pd-O-H) functionalities alongside phenyl (Ph) groups. Right Section: Lists the applications of this setup, including Kinetic Studies, Isotope-Labeling, and High-Resolution Mass Spectrometry, all marked with check marks. The entire diagram emphasizes the synthesis process and subsequent mass spectrometric analysis of the products.

Figure 2: Styrene oxidation by a PBOPd(OTf)2 catalyst and H2O2 revealed key intermediates

The Ru complex (DTBPY)2RuCl2 has been shown to be a competent C-H hydroxylation catalyst for substrates that contain amines and azacycles under acidic and strongly oxidizing conditions.8 Recently, with PSI-MS, the speciation of the Ru(II) catalyst during a reaction was monitored, and Ru(IV), Ru(V), and Ru(VI) were all observed (Figure 3). Both Ru(V) and Ru(VI) may be responsible for product formation. Also, the loss of ligand and the formation of oxidized ligand occurs concomitantly with the production of high oxidation Ru. Ongoing studies are being conducted to quantify the ligand loss and the other degradation pathways.

A chemical reaction schematic illustrating the transformation of a substrate.Left Section: Shows a starting compound with a benzyl ether group (BzO) and two methyl (Me) groups on a carbon chain. Arrow: Indicates the progression of the reaction with the following conditions: 5 mol% of a ruthenium complex (cis-[Ru(dtbpy)₂CO₃]) used as a catalyst in the presence of 2 equivalents of hydrogen iodide (H₅IO₆), and acetic acid (AcOH) mixed with water (H₂O) in a 1:1 ratio. Right Section: Displays the product, which has a hydroxyl group (OH) added to one of the carbon atoms of the chain. Bottom Section: Contains structural representations of the ruthenium complex catalysts, showing t-butyl (tBu) groups and acetate (OAc) functionalities attached to the ruthenium center and nitrogen atoms. The diagram summarizes a specific chemical transformation involving a catalytic process and the resulting product.

Figure 3: Ru-catalyzed C-H hydroxylation

1. Ingram, A. J.; Boeser, C. L.; Zare, R. N., Chemical Science 2016, 7, 39-55.

2. Davis, D. C.; Walker, K. L.; Hu, C.; Zare, R. N.; Waymouth, R. M.; Dai, M., J. Am. Chem. Soc. 2016, 138, 10693-10699.

3. Ingram, A. J.; Walker, K. L.; Zare, R. N.; Waymouth, R. M., J. Am. Chem. Soc. 2015, 137, 13632-13646.

4. Theron, R.; Wu, Y.; Yunker, L. P. E.; Hesketh, A. V.; Pernik, I.; Weller, A. S.; McIndoe, J. S., ACS Catalysis 2016, 6, 6911-6917.

5. Cao, Q.; Bailie, D. S.; Fu, R.; Muldoon, M. J., Green Chemistry 2015, 17, 2750-2757.

6. Walker, K. L.; Dornan, L. M.; Zare, R. N.; Waymouth, R. M.; Muldoon, M. J., J. Am. Chem. Soc. 2017, 139, 1249512503.

7. Michel, B. W.; Steffens, L. D.; Sigman, M. S., J. Am. Chem. Soc. 2011, 133, 8317-8325.

8. Mack, J. B. C.; Gipson, J. D.; Du Bois, J.; Sigman, M. S., J. Am. Chem. Soc. 2017, 139, 9503-9506.