The Development of Late Transition Metal Catalysis for Hydrocarbon C-H Activation: Studies of Ru, Pd, Rh and Cu

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Jia, Xiaofan, Chemistry - Graduate School of Arts and Sciences, University of Virginia
Gunnoe, Thomas, AS-Chemistry, University of Virginia

Olefin hydroarylation, also called arene alkylation, via late transition metal mediated C–H activation provides a pathway for the production of alkyl arenes that are produced on large scale from arenes and olefins. Late transition metal catalyzed arene alkyl-/alkenylation offers opportunities to overcome drawbacks of commercial acid-catalyzed arene alkylation including polyalkylation, an inability to generate anti-Markovnikov addition products for reactions with a-olefins, and substrate controlled regioselectivity for reactions with substituted arenes.
Olefin hydroarylation catalysts based on TpRu(II) (Tp = trispyrazolylborate) complexes have been shown to generate ethylbenzene from benzene and ethylene. Previous studies have shown that TpRu(II) catalysts with lower electron density can achieve higher catalytic turnovers. In this thesis, four new TpRu complexes and derivatives are reported. TpRu(NO)Ph2 exhibited low stability due to the facile reductive elimination of the phenyl group. (TpBr3)Ru(NCMe)(Ph)(P(OCH2)3CEt) showed no catalytic activity due to the steric bulk introduced by the bromine substituents. (TTz)Ru(NCMe)(Ph) (P(OCH2)3CEt) (TTz = hydrotris(1,2,4-triazol-1-yl)borate) gave ~150 turnover numbers (TONs) of ethylbenzene. Ru catalysts supported by tris-triazyl ligands, LnRu(P(OCH2)3CEt)(NCMe)Ph {Ln = CH3OTMM (4,4',4"-ethoxyethanetriyl)tris(1-benzyl-1H-1,2,3-triazole), PhTTM (tris(1-phenyl-1H-1,2,3-triazol-4-yl)methanol), is demonstrated to be selective toward styrene production. The selectivity of styrene versus ethylbenzene varies as a function of ethylene pressure, and replacing the MeOTTM ligand with PhTTM reduces the selectivity toward styrene. Our studies show that ethylene serves as the hydrogen acceptor (oxidant) in this Ru catalyzed arene alkenylation reaction.
Pd(OAc)2 has been reported to catalyze the conversion of arenes and olefins to vinyl arenes, although generally with low selectivity. Commonly observed side products include vinyl carboxylates and stilbene. The selectivity for styrene formation by Pd(OAc)2 is studied as a function of reaction temperature, ethylene pressure, Brønsted acid additive, Cu(II) oxidant amount, and oxygen pressure. Under optimized conditions, at high temperatures (180 °C) and low olefin pressure (20 psig), nearly quantitative yield (> 95%) of styrene is produced based on the limiting reagent copper(II) pivalate. We propose the selectivity for styrene versus vinyl pivalate at 180 °C is due to a newly elucidated palladium-catalyzed conversion of benzene and in situ formed vinyl pivalate to styrene.
A systematic investigation of the differences in Pd and Rh catalyzed arene alkenylation reactions is described in this thesis. The selectivity for vinyl ester vs. alkenyl arene is probed by using the ethylene hydrophenylation reaction as a model. The regioselectivity for -olefin hydrophenylation is examined using propylene. Four alkenylated products are observed: allylbenzene, -trans-methylstyrene, -cis-methylstyrene and -methylstyrene. There are two primary differences for Pd vs. Rh catalysis. First, the L:B ratio (linear = anti-Markovnikov products; branched = Markovnikov products) for Rh catalyzed reactions is greater than the Pd catalyzed processes. Second, the ratio of allylbenzene to -trans-methylstyrene varies greatly between Rh (1.2) and Pd (0.06). We also compared the regioselectivity between Rh and Pd catalysis in reactions with mono-substituted arenes and found that Rh catalysis has better higher selectivity for meta functionalization, and Rh is better able to tolerate the presence of halogen groups.
A single step synthetic method for stilbene and its derivatives is described here based on our well-studied Rh-catalyzed arene alkenylation chemistry. The synthesis involves direct C–H activation, eliminating the need for additional steps to install leaving or directing groups, thereby reducing stoichiometric waste. A substoichiometric amount of copper(II) salt is used as a direct oxidant, which is regenerated by dioxygen from air in situ, making dioxygen the terminal oxidant. Also, we have investigated the scope of the catalysis using a wide range of arenes with different functional groups. This catalysis has shown a great tolerance to functionalities including fluoro, chloro, trifluoromethyl, ester, nitro, acetoxy, cyano and ether groups. The unique tolerance to halogen groups, especially of bromo and iodo groups, allows for facile further functionalization of the substrates. Two compounds of pharmacological interest, Resveratrol and DMU-212 {(E)-1,2,3-trimethoxy-5-(4-methoxystyryl)benzene}, were synthesized from this single-step approach, and it has been demonstrated that this synthetic method can be used in gram-scale synthesis using a very simple reaction setup.
Additionally, water oxidation using multinuclear [(DAM)Cu3(μ3-O)][Cl4] (DAM = dodecaaza macrotetracycle) complexes is reported. Turnover frequencies (TOFs) of 14.0 s-1 at pH 7 and 17.7 s-1 at pH 8.2 are observed. We have discovered that the [DAMCu3(μ3-O)][Cl4] remains active for water oxidation under acidic conditions. [DAMCu3(μ3-O)][Cl4] also shows activity as an light alkane oxidation catalyst. Under optimized conditions, partial oxidation of methane to methanol with hydrogen peroxide was observed with 179% yield relative to copper catalyst under 30 bars of methane after 12 hours reaction at room temperature

PHD (Doctor of Philosophy)
Olefin Hydroarylation, Catalysis, Palladium, Ruthenium, Rhodium, Water Oxidation, Stilbene
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