Computational modeling to explore unconventional reactivity patterns in c−h activation and boron chemistry
- Autores: Diego Garcia López
- Directores de la Tesis: Jorge Juan Carbó Martín (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Elena Fernández Gutiérrez (presid.), Alberto Roldan Martínez (secret.), Victoriano Polo Ortiz (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencia y Tecnología Química por la Universidad Rovira i Virgili
- Materias:
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- Resumen
The rapid progress that computational power has undergone during recent years has emerged as a valuable tool for helping to solve the experimental chemistry aspirations, such as unraveling reactions mechanism, predict the activity of compounds or describe microscopic interactions throughout time. In this context, this thesis attempts to combine both computational and synthetic chemistry domains since is largely based on collaborations with experimental groups in order to unveil the ultimate forces governing particular processes, but also employs modeling techniques to predict the outcome of yet untested chemical phenomena.
After the introduction and goals of this thesis (Chapters 1, 2 and 3), the first part deals with the activation of inert C−H bonds (Chapters 4 and 5). This field of inquire has been one of the main topics in organometallic chemistry during last years since transition-metal-based systems are able to cleave the C−H linkage under mild conditions and in the absence of oxidant agents. Activation and posterior functionalization of the omnipresent C−H bond may allow the conversion of cheap and abundant organic compounds into valuable molecules while providing synthetic shortcuts to desirable products. Despite the great challenge displayed by this reactivity, many efforts are devoted in understand this chemical transformation and design new process to overcome its inherent difficulties.
In Chapter 4, we determined computationally the mechanism of remote C−H activation on titanium dinuclear complexes ([{Ti(η5-C5Me5)R2}2(μ-O)], R = CH2SiMe3, CH2CMe3, and CH2Ph) that has been observed by the group of Dr. Santamaría at the University of Alcalá. DFT calculations show that the mechanism involves a first α-hydrogen abstraction to generate a transient titanium alkylidene, which enables it to activate β- and γ-C(sp3)−H bonds on the adjacent titanium center. The calculations also establish a reactivity order for the different type of γ-H abstractions, trimethylsilyl > neopentyl ≈ benzyl, allowing us to explain the experimental selectivity.
In Chapter 5, we interpreted the rare Ni−(C[Ar]−H) interaction in solid state structure of [NiBr(κ3-P,N,(C−H)-L)]BF4 observed by the group of Prof. van der Vlugt at the University of Amsterdam. This structure can be directly related to a fast and facile C−H cyclometalation at the NiII center. The theoretical study includes the quantum theory of atoms in molecules (QTAIM) and electron localization function (ELF) analysis which characterize the nature of the Ni−(C[Ar]−H) bond as a bona fide albeit weak (an)agostic coordinative interaction, with predominant Ni−(η1-C[Ar]) character.
The second part concerns boron chemistry and it was performed in collaboration with Dr. Elena Fernández at the Universitat Rovira i Virgili (Chapters 6, 7 and 8). This atom typically comprises three linkages forming trivalent compounds that have been traditionally regarded as electrophilic agents. However, boryl synthons can change their electrophilic character towards a nucleophilic behavior depending on the nature of the substituents attached to the boron atom. Indeed, suitable ligands are capable of supplying enough electron density so that yield the boron nucleus unable to stabilize the excess of negative charge and seeks for other atoms to bond with. This recent discovery of the nucleophilic performance of these species represents a milestone in organic synthesis. Furthermore, non-conventional routes for the functionalization of unsaturated bonds in organic molecules under metal-free conditions by diboron compounds are beginning to appear. Concerning boron-interelement reagents, the reactivity might offer a wider scope via push-pull effect. Hence, the versatility and reaction conditions offered by boryl synthons make them attractive for the construction of carbon-carbon and carbon-heteroatom bonds.
In Chapter 7, we described the development of quantitative structure-activity relationships (QSAR) for the nucleophilic activity of trivalent boron compounds, covering boryl fragments bonded to alkali and alkaline-earth metals, to transition metals, and to sp3 boron units in diboron reagents. Multivariate regression techniques were carried out for determining a quantitative relationship between ground-state properties and nucleophilic activity. The descriptors chosen were the charge of the boryl fragment (q[B]) and the boron p/s orbital population ratio (p/s) to describe the electronic structures of boryl moieties, whereas the distance-weighted volume (VW) descriptor was used to evaluate the steric effects. The resulting three-term easy-to-interpret QSAR model showed statistical significance and predictive ability (r2 = 0.88, q2 = 0.83). The use of chemically meaningful descriptors has allowed identification of the factors governing the boron nucleophilicity and indicates that the most efficient nucleophiles are those with enhanced the polarization of the B−X bond towards the boron atom and reduced steric bulk. Also, we used the QSAR model to make a priori predictions of experimentally untested compounds. Finally, we built specific QSAR models for the nucleophilicity of transition metal-free boron reagents including symmetric and asymmetric diboron reagents activated by Lewis bases, as well as boron-interelement compounds. In Chapter 7, the heterolytic cleavage of the mixed diboron reagent, pinB–Bdan, and the formation of two geminal C–Bpin and C–Bdan bonds was rationalised based on DFT calculations to occur via a concerted yet asynchronous mechanism. Diastereoselection is attained on substituted cyclohexanones and such computational studies provide understanding on the origin of the selectivity. We also studied the observed alkoxide-assisted, selective deborylation of Bpin from multisubstituted sp3-carbon via generation of a Bdan stabilized carbanion that easily conducts to a selective protodeboronation sequence.
In Chapter 8, theoretical calculations rationalized the observed regio- and stereoselectivity of the anti-3,4-selenoboration of α,β- acetylenic esters and ynamides using catalytic amounts of PCy3. Interestingly, in the absence of phosphine the selenoboration switched from the formation of α-vinyl selenides to β-vinyl selenides. The computational study discovered a novel mechanism which differs from previous mechanistic proposals for analogous anti-selective carboration, silaboration and diboration. The phosphine adds to the β position of the alkynoate switching the polarity of the triple bond and favoring the 1,3-selenoboration which produces the α-addition of selenyl group. Then, the autocatalytic action of a second selenoborane reagent, which coordinates to the phosphorus ylide intermediate, determines the stereoselectivity and completes the catalytic process.
Finally, a summary of the conclusions is presented in Chapter 9.
