WILLIAMS, LUKE,JAMIE (2022) Aromatic Transformations Facilitated by η6–Coordination to Ruthenium (II). Doctoral thesis, Durham University.
|PDF (PhD Thesis) - Accepted Version
Over the last 70 years the chemistry of η6-arene transition metal complexes has been extensively developed, with the enhancement of aromatic reactivity through complexation being applied to extensive number of different synthetic targets. On η6-complexation to a metal, a C6-aromatic ring becomes much more susceptible to nucleophilic attack (SNAr), while the deprotonation of both aromatic and benzylic sites is made much more facile than for free arenes. Furthermore, the activating MLn fragment blocks the face of the aromatic ring it is bound to, meaning any attacks on the ring are inherently directed towards the free face, thus giving some steric control over the reactivity. Since the turn of the millennium, a resurgence in this field of organometallic chemistry has occurred with the realisation of metal-catalysed aromatic transformations via transient η6-coordination of the arene. Through an arene exchange process, the bound transformed aromatic ring can exchange with the starting material to regenerate the initial η6-arene complex, giving catalytic turnover. In this thesis, four projects exploring the reactivity of η6-arene complexes of ruthenium(II), their arene exchange and finally ruthenium-catalysed aromatic transformations via transient coordination.
The first project described is the attempted nucleophilic fluorination and difluoromethylations of arenes bound η6- to an activating [RuCp]+ fragment. The complex [(η6-C6H6)RuCp]+ was reacted with a series of different nucleophilic sources of fluoride, with only TBAF exhibiting any sort of reactivity. Due to the presence of moisture in the reaction, addition of a hydroxy group to the ring occurred, resulting in the formation of an η5-cyclohexadienyl (Meisenheimer) complex, which proved too unstable to isolate, while attempts at in-situ oxidation of the ring resulted in decomposition of the complex. Difluoromethylation of the complex [(η6-C6H5CN)RuCp]+ using the reagent CF2HSiMe3 in the presence of base and fluoride resulted in ortho-addition of a hydroxy group to the bound benzonitrile ring, giving another Meisenheimer complex. Unlike the previous one, this complex was sufficiently stable under ambient conditions to be isolated and characterised, while attempts to oxidise the ring resulted in formation of a free arene, most likely to be 2-cyanophenol.
The next project revolves around an enolate SNAr reaction of the aromatic ring in the complexes [(C6H5X)RuCp]+ (where X = leaving group), resulting in the formation of bound 2-aryl-1,3-diones. The presence of methyl groups ortho to the leaving group hindered the reaction significantly, as an increased temperature was required to facilitate SNAr. Experiments on rings containing multiple different leaving groups were used to establish the chemoselectivity of the SNAr on the bound ring, while a broad range of cyclic diones were successfully tested under the reaction conditions. Following the SNAr transformation, the free aromatic product could be liberated from the ruthenium centre by irradiating an acetonitrile solution of the complex with UV light. While attempts to translate the enolate SNAr into a process catalytic in ruthenium were unsuccessful, a one-pot stepwise synthesis of the free aromatic product, in which the activating [RuCp]+ fragment could be recycled was achieved.
The arene exchange of the complexes [(η6-arene)RuCp(*)]+ with hexamethylbenzene were investigated and the effects of changing the temperature and irradiating the system were established. Also, the tether-assisted arene exchange of a library of sandwich complexes containing Cp rings functionalised with tethered coordinating groups was explored, and enhanced rates of arene exchange were observed for some of the tether complexes.
Finally, two ruthenium-catalysed aromatic transformations proposed to occur via temporary η6-coordination were explored and optimised. The first was a previously established catalytic SNAr amination of 4-chlorotoluene, where the complexes bearing tethered coordinating groups were tested for their activity. A stoichiometric study on the SNAr amination with morpholine proved the existence of the suspected resting state of the catalytic cycle, [(η6-N(4-tolyl)morpholine)RuCp]+. Next, a ruthenium-catalysed hydrodeiodination of aryl iodides was further optimised with shorter reaction times under microwave heating. Further experiments were performed on iodoarenes functionalised with electron-donating or electron-withdrawing groups to obtain insight on the reaction mechanism and infer the nature of charge build-up in the transition state.
|Doctor of Philosophy
|η6–Coordination Aromatic Transformations Ruthenium (II) Nucleophilic Aromatic Substitution Arene Exchange Catalysis
|Faculty and Department:
|Faculty of Science > Chemistry, Department of
|Copyright of this thesis is held by the author
|07 Nov 2022 14:15