Abstract
Alkenylarenes are an important class of compounds because they serve as precursors to both large volume commodity chemicals and high value pharmaceuticals. For example, ethylbenzene was produced on a scale of ~40 million tonnes in 2018, 38 million tonnes of which were used to produce styrene. Styrene production is expected to increase to ~50 million tonnes by 2030. The current industrial route to produce styrene involves an energy intensive acid-catalyzed process using Friedel-Crafts chemistry or zeolites followed by a dehydrogenation step. An alternative catalytic process to synthesize alkenyl arenes is using transition-metal catalysts that are active for C–H functionalization. These new routes to alkenyl arenes offer potential advantages when compared to acid-catalyzed processes including selectivities that are unique and different. However, further advancements in the field of C–H functionalization need to be made before it can be considered for scalable industrial synthesis. If the development of more energy-efficient catalytic processes to synthesize alkenyl arenes could become commercially viable, benefits such as energy savings, waste reduction and access to new chemicals would be possible.
Our group has reported that the Rh(I) catalyst precursor [(η2-C2H4)2Rh(μ-OAc)]2 and oxidant Cu(X)2 (X = carboxylate) are active for arene alkenylation. The proposed mechanism involves transition-metal mediated C–H activation to form a metal–aryl bond. Olefin insertion into the metal–aryl bond and β-hydride elimination to form a M–H bond and a transiently bound alkenyl arene. Reaction of the M–H with 2 Cu(X)2 will regenerate the starting catalytic species and release the alkenyl arene product. Rh-catalyzed oxidative arene alkenylation offers several advantages compared to acid-catalyzed processes including the direct synthesis of alkenyl arenes in one step and unique selectivities with substituted benzenes and α-olefins. Extension of this chemistry towards substrates such as anisole, naphthalene and disubstituted benzenes reveals the potential for access to new types of chemicals and new conclusions about the reaction mechanism.
Chapter 2 describes the conversion of anisole and olefins (ethylene or propylene) to alkenyl anisoles. Most notably, trans-anethole, a bioactive molecular of interest, can be synthesized with a 50% selectivity in two steps from anisole and propylene. The o:m:p ratios depend on concentration of acid additive and olefin. Mechanistic studies of the conversion of anisole and olefins to alkenyl anisoles provides evidence that the regioselectivity is likely under Curtin-Hammett conditions.
In Chapter 3, the direct conversion of naphthalene and olefins (i.e., ethylene and propylene) to alkenylnaphthalenes is discussed. Under all reaction conditions tested, the functionalization is selective for the β-position of naphthalene. The β-selectivity is catalyst controlled, but oxidant identity, ethylene pressure and olefin identity influence the ratio of β-alkenylation to α-alkenylation. Arenes similar to naphthalene (i.e., o-xylene and 1,2,3,4-tetrahydronaphthalene) give quantitative selectivity for alkenylation at the position β to the substituent.
Chapter 4 reports on the direct ethenylation of 1,3- and 1,2-disubstituted benzenes. The regioselectivity of alkenylation for 1,3-disubstituted benzenes quantitatively produces the 3,5-disubstituted styrene product while the alkenylation of 1,2-disubstituted benzenes quantitatively produces the 3,4-disubstituted styrene product. Alkenylation of asymmetric 1,2-disubstituted benzenes gives a mixture of isomers that depends on the arene substituents. The rate of alkenylation is influenced by both steric and electronic factors. Interestingly, the rate of alkenylation is influenced by arene substituent electronics. The rate of alkenylation for 1,2-disubstituted benzenes increases with increasing electron-donating substituents (i.e., OMe > Me > CF3 > Cl) while for 1,3-disubstituted benzenes, the opposite is true with increasing rate with increasing electron-withdrawing substituents (i.e., CF3 > Cl > Me). Mechanistic studies propose that the mechanism of C–H activation changes depending on the arene substituents.
Chapter 5 outlines heterogeneously catalyzed arene alkenylation. The molecular Rh complex Rh(acac)(C2H4)2 was supported on the metal organic framework (MOF) UiO-67 to produce a solid material, Rh@UiO-67. Rh@UiO-67 catalyzes the alkenylation of benzene and toluene with ethylene to produce styrene and methylstyrenes. Furthermore, the reaction of benzene and propylene produces propenylbenzenes. Rh@UiO-67 shows long-lived catalysis, producing 515(68) TOs of styrene after 196 hours at 190 °C with no indication of catalyst deactivation.
Lastly, Chapter 6 provides potential future directions for Rh-catalyzed oxidative arene alkenylation. The first future direction expresses the potential of Rh-catalyzed oxidative alkenylation to impact fine chemical synthesis by providing a route to directly synthesize important methoxy- and hydroxy-substituted alkenyl benzene precursors. The second future direction describes the potential for oxidative arene alkenylation to contribute to the study of oxidatively resistant synthetic base oils by derivatizing naphthalene. The third future direction outlines pathways to improve upon heterogeneously catalyzed styrene production by supporting molecular Rh and Ir complexes.
