Mechanisms, mass spectrometry & microdroplets : using high-resolution mass spectrometry to elucidate catalytic organometallic reaction mechanisms

Chapter 1: A summary of some recent work on reaction acceleration and novel reactivity within microdroplets. Specifically, the strengths and weaknesses of electrospray ionization mass spectrometry (ESI), sonic spray ionization (SSI), pressurized sample infusion (PSI), matrix-assisted laser desorption ionization (MALDI), and atmospheric pressure chemical ionization (APCI) are discussed. Chapter 2: A palladium-catalyzed cascade carbonylative spirolactonization of hydroxycyclopropanols has been developed to efficiently synthesize oxaspirolactones common to many complex natural products of important therapeutic value. Mechanistic studies utilizing high-resolution electrospray ionization mass spectrometry (ESI-MS) identified several key intermediates in the catalytic cycle as well as those related to catalyst decomposition and competitive pathways. Chapter 3: Kinetic studies, isotope labeling, and in situ high-resolution mass spectrometry are used to elucidate the mechanism for the catalytic oxidation of styrenes using aqueous hydrogen peroxide (H2O2) and the cationic palladium(II) compound, [(PBO)Pd(NCMe)2]OTf2 (PBO = 2-(pyridin-2-yl)benzoxazole). Previous studies have shown that this reaction yields acetophenones with high selectivity. We find that H2O2 binds to Pd(II) followed by styrene binding to generate a Pd-alkylperoxide that liberates acetophenone by at least two competitive processes, one of which involves a palladium enolate intermediate that has not been previously observed in olefin oxidation reactions. We suggest that acetophenone is formed from the palladium enolate intermediate by protonation from H2O2. Chapter 4: [(dtbpy)2RuCl2] is an effective precatalyst for chemoselective C--H hydroxylation of C(sp3)--H bonds, but we have noted a marked disparity in reaction performance between 4,4'-di-tert-butyl-2,2'-bipyridine (dtbpy)- and 2,2'-bipyridine (bpy)-derived complexes. Details of this reaction have been unveiled through evaluation of ligand structure-activity relationships, electrochemical and kinetic studies, and pressurized sample infusion high-resolution mass spectrometry (PSI-MS). We identify more than one active oxidant and three disparate mechanisms for catalyst decomposition/arrest. Catalyst efficiency, as measured by turnover number, has a strong inverse correlation with the rate and extent of ligand dissociation, which is dependent on the identity of bipyridyl 4,4'-substituent groups. Dissociated bipyridyl ligand is oxidized to mono- and bis-N-oxide species under the reaction conditions, the former of which is found to act as a potent catalyst poison, yielding a catalytically inactive tris-ligated [Ru(dtbpy)2(dtbpy-N-oxide)]2+ complex. Insights gained through this work highlight the power of PSI-MS for studies of complex reaction processes. Chapter 5: A recently reported dimeric salen-chromium complex enantioselectively polymerizes propylene oxide. Polymerization is proceeds efficiently with the optimized catalyst system, but only after a period where the catalyst sits dormant and only short oligomers are formed. We undertook a detailed mechanistic study with the use of high resolution electrospray ionization mass spectrometry (ESI-MS) and DFT calculations to determine the chromium species responsible for this lag phase. MS reveals that chromium hydroxide and chromium-bound 1,2-diols are present during this dormant period, and kinetic studies show that these species are responsible for an arrest state. In-situ MS shows that the chromium hydroxide reacts with propylene oxide to generate chromium-bound 1,2-diols. Chapter 6: Efficient, direct synthesis of hydrogen peroxide, H2O2, from water is a current challenge. Here we show H2O2 is spontaneously produced from pure water by atomizing bulk water into microdroplets (1-20 μm in diameter). Production of H2O2 is assayed by a H2O2-sensitive fluorescent dye, mass spectrometry, NMR, and UV-visible light spectroscopy of H2O2-sensitive dyes. Bubbling O2 decreased the yield of H2O2 in microdroplets, indicating that H2O2 is directly generated from pure water and not from O2 dissolved in water. The generated H2O2 concentration was ~30 μM. This catalyst-free and voltage-free H2O2 production method provides new opportunities for green production of hydrogen peroxide.

Keywords: Chemistry.
Advisor: Waymouth Robert M. 
Zare Richard N. 
Burns Noah