Cooperative Reactivity of Boron-Containing Molecules and Lewis Bases for Metal Free Catalysis

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2015-2016La catalyse par métaux de transition est omniprésente de nos jours dans tous les secteurs de l’industrie chimique. Les réactions activées de cette façon permettent la production d’un grand nombre de produits utiles de grande importance commerciale. Considérant uniquement le domaine de la synthèse organique, le développement de réactions catalytiques a été récompensé par plusieurs prix Nobel au cours du 20e siècle, ce qui témoigne de l’importance de ces contributions. L’utilisation de métaux de transition, et surtout des métaux précieux, en catalyse comprend cependant des inconvénients qui proviennent de leur coût élevé, de leur rareté, ainsi que de leur toxicité potentielle et de l’impact environnemental que leurs déchets peuvent avoir. De fait, plusieurs agences nationales et internationales régulent de nos jours la teneur en métaux à l’état de traces qui peuvent être présents dans beaucoup de produits. Pour cette raison, il est de grand intérêt de découvrir des systèmes catalytiques alternatifs composés d’éléments abondants, non-toxiques et peu coûteux. Le bore, en tant qu’élément léger du groupe principal, répond à ces critères. Cependant, la réactivité des composés organoborés est très différente de celle des métaux de transition et peu adaptée aux réactions catalytiques existant de nos jours. Pour cette raison, de nouveaux concepts et de nouvelles réactions doivent être inventés et développés afin d’introduire le bore au domaine de la catalyse. Dans le but de développer de tels concepts, et dans le but de concevoir de nouveaux catalyseurs à base de bore, nous avons investigué plusieurs cas où la présence de bases de Lewis influence la réactivité de composés borés. Notre hypothèse était que la combinaison d’un organoboré et d’une base de Lewis pourrait agir dans des réactions qui seraient impossibles pour chacun individuellement. Dans une première étude de cas, nous avons étudié en profondeur la réactivité d’adduits neutres de borabenzène vis-à-vis de bases de Lewis. Nous avons ainsi trouvé que, contrairement au formalisme courant, le borabenzène coordonné à une base réagit comme un nucléophile plutôt qu’un électrophile. Les propriétés et la réactivité de nombreux composés à base de borabenzène ont été étudiées par des méthodes computationnelles et expérimentales en une recherche qui est présentée dans cette thèse. Par la suite, nous nous sommes penchés sur le problème de la réduction du dioxyde de carbone catalysée par des composés organoborés ambiphiles. À l’issu de ce travail, nous décrivons de nouveaux modes d’interaction entre le bore et des bases de Lewis inusités et les applications de ces concepts à la réduction du CO2 en dérivés de méthanol. Finalement, nos travaux de recherche culminent avec le développement d’un catalyseur ambiphile sans métal pour l’activation et la borylation des liens C-H d’hétéroarènes. Dans cette thèse, nous décrivons le processus de réflexion qui a mené à la conception rationnelle de cette réaction, ainsi que les propriétés uniques de ce système.Transition metal catalysis is currently ubiquitous in all sectors of the chemical industry. The reactions it enables allow the production of countless useful chemicals. In the field of organic synthesis alone, the impact and development of catalytic reactions have been recognized several times by the award of Nobel prizes. The use of transition metals for catalysis, however, suffers from several drawbacks that include their high cost, their rarity and their potential toxicity and environmental impact. National and international agencies, as a matter of fact, regulate the trace amounts of residual metal that can be present in many end products. For this reason, there is great interest in discovering alternative catalysts produced from earth-abundant, nontoxic and inexpensive elements. Boron, as a light element of the main group, follows these criteria. The reactivity of organoboron compounds, however, is very different from that of organometallic complexes, and less adapted to typical catalytic process. For this reason, new concepts and new reactions have to be developed in order to introduce boron to the world of catalysis. In order to discover and develop novel ideas towards the design of boron catalysts, we have studied different instances in which Lewis bases influence the reactivity of boron compounds. We hypothesized that the combination of an organoborane and a Lewis base could achieve reactions that would be impossible for the separate units to accomplish. In a first case study, we have investigated in depth the reactivity of neutral adducts of borabenzene towards Lewis bases. We have found that, contrary to usual formulations, borabenzene, under the influence of a Lewis base, reacts as a nucleophile rather than an electrophile. The properties and reactivity of a great number of borabenzene compounds have been studied computationally and experimentally in a work that will be presented in this dissertation. Next, we have studied the reduction of carbon dioxide catalyzed by ambiphilic organoboron compounds. We describe new modes of coordination for boranes with Lewis bases and the application of these interactions to the reduction of CO2 to methanol derivatives. Finally, the culmination of our research efforts is shown as the rational development of a metal-free ambiphilic catalyst for the C-H bond activation and borylation of heteroarenes. In this dissertation, we describe the process by which we designed and implemented this catalytic reaction, as well as the specifics of the system

Metal-free catalytic C-H bond activation and borylation of heteroarenes

Transition metal complexes are efficient catalysts for the C-H bond functionalization of heteroarenes to generate useful products for the pharmaceutical and agricultural industries. However, the costly need to remove potentially toxic trace metals from the end products has prompted great interest in developing metal-free catalysts that can mimic metallic systems. We demonstrated that the borane (1-TMP-2-BH2-C6H4)2 (TMP, 2,2,6,6-tetramethylpiperidine) can activate the C-H bonds of heteroarenes and catalyze the borylation of furans, pyrroles, and electron-rich thiophenes. The selectivities complement those observed with most transition metal catalysts reported for this transformation

Reducing CO2 to methanol using frustrated Lewis pairs : on the mechanism of phosphine-borane mediated hydroboration of CO2

The full mechanism of the hydroboration of CO2 by the highly active ambiphilic organocatalyst 1-Bcat-2-PPh2-C6H4 (Bcat = catecholboryl) was determined using computational and experimental methods. The intramolecular Lewis pair was shown to be involved in every step of the stepwise reduction. In contrast to traditional frustrated Lewis pair systems, the lack of steric hindrance around the Lewis basic fragment allows activation of the reducing agent while moderate Lewis acidity/basicity at the active centers promotes catalysis by releasing the reduction products. Simultaneous activation of both the reducing agent and carbon dioxide is the key to efficient catalysis in every reduction step

A highly active phosphine-borane organocatalyst for the reduction of CO2 to methanol using hydroboranes

In this work, we report that organocatalyst 1-Bcat-2-PPh2-C6H4 ((1); cat = catechol) acts as an ambiphilic metal-free system for the reduction of carbon dioxide in presence of hydroboranes (HBR2 = HBcat (catecholborane), HBpin (pinacolborane), 9-BBN (9-borabicyclo[3.3.1]nonane), BH3·SMe2 and BH3·THF) to generate CH3OBR2 or (CH3OBO)3, products that can be readily hydrolyzed to methanol. The yields can be as high as 99% with exclusive formation of CH3OBR2 or (CH3OBO)3 with TON (turnover numbers) and TOF (turnover frequencies) reaching >2950 and 853 h(-1), respectively. Furthermore, the catalyst exhibits "living" behavior: once the first loading is consumed, it resumes its activity on adding another loading of reagents

Phosphazenes : efficient organocatalysts for the catalytic hydrosilylation of carbon dioxide

Phosphazene superbases are efficient organocatalysts for the metal-free catalytic hydrosilylation of carbon dioxide. They react with CO2 to form the respective phosphine oxides, but in the presence of hydrosilanes, CO2 can be selectively reduced to silyl formates, which can in turn be reduced to methoxysilanes by addition of an extra loading of silanes. Activities reach a TOF of 32 h−1 with a TON of 759. It is also shown that unexpectedly, N,N-dimethylformamide can reduce CO2 to a mixture of silyl formates, acetals and methoxides in the absence of any catalyst

Bench-stable frustrated Lewis pair chemistry : fluoroborate salts as precatalysts for the C-H borylation of heteroarenes

While the organotrifluoroborate group is commonly used as a leaving group in cross-coupling reactions, we now show that their high stability can be used to protect the Lewis acidic moieties of frustrated Lewis pair catalysts. Indeed, the air and moisture-stable trifluoro- and difluoroborate derivatives of bulky (tetramethylpiperidino)benzene are shown to be conveniently converted to their dihydroborane analogue which is known to activate small molecules. An efficient synthesis route to these stable and convenient precatalysts, their deprotection chemistry and their benchtop use for the dehydrogenative borylation of heteroarenes is presented

Intramolecular B/N frustrated lewis pairs and the hydrogenation of carbon dioxide

The FLP species 1-BR2-2-NMe2-C6H4 (R = 2,4,6-Me3C6H21, 2,4,5-Me3C6H22) reacts with H2 in sequential hydrogen activation and protodeborylation reactions to give (1-BH2-2-NMe2-C6H4)23. While 1 reacts with H2/CO2 to give formyl, acetal and methoxy-derivatives, 2 reacts with H2/CO2 to give C6H4(NMe2)(B(2,4,5-Me3C6H2)O)2CH24. The mechanism of CO2 reduction is considered

A tris(triphenylphosphine)aluminum ambiphilic precatalyst for the reduction of carbon dioxide with catecholborane

The ambiphilic species Al(C6H4(o-PPh2))3 (2) was synthesized and fully characterized, notably using X-ray diffraction. Species 2 exhibits pseudo-bipyramidal-trigonal geometry caused by the two Al–P interactions. 2 reacts with CO2 to generate a CO2 adduct commonly observed in the activation of CO2 using frustrated Lewis pairs (FLPs). This ambiphilic species serves as a precatalyst for the reduction of CO2 in the presence of catecholborane (HBcat) to generate CH3OBcat, which can be readily hydrolyzed in methanol. The reaction mixture confirms that, in the presence of HBcat, 2 generates the known CO2 reduction catalyst 1-Bcat-2-PPh2-C6H4 (1) and intractable catecholate aluminum species. It was, however, possible to isolate a single crystal of Al(κ2O,O-(MeO)2Bcat)3 (5) supporting this hypothesis. Also, a borane-protected analogue of 2, Al(C6H4(o-PPh2·BH3))3 (4), does not react with catecholborane, suggesting the influence of the pendant phosphines in the transformation of 2 into 1

Reactivity of a Cl-boratabenzene Pt(II) complex with Lewis bases : generation of the kinetically favoured Cl-boratabenzene anion

Complex [(IMes)2Pt(H)(ClBC5H4SiMe3)] (IMes = 1,3-di(2,4,6-trimethylphenyl)imidazolin-2-ylidene) reacts with Lewis bases (L = pyridine, trimethylphosphine, acetonitrile, tert-butylisocyanide) to generate the kinetically favoured ion pairs [(IMes)2Pt(H)(L)][ClBC5H4SiMe3]. Over time, the formation of the thermodynamically favoured borabenzene-L adducts is observed with L = pyridine and trimethylphosphine

Synthesis of carboxylate Cp*Zr(IV) species : towards the formation of novel metallocavitands

With the intent of generating metallocavitands isostructural to species [(CpZr)3(μ(3)-O)(μ(2)-OH)3(κO,O,μ(2)-O2C(R))3](+), the reaction of Cp*2ZrCl2 and Cp*ZrCl3 with phenylcarboxylic acids was carried out. Depending on the reaction conditions, five new complexes were obtained, which consisted of Cp*2ZrCl(κ(2)-OOCPh) (1), (Cp*ZrCl(κ(2)-OOCPh))2(μ-κ(2)-OOCPh)2 (2), [(Cp*Zr(κ(2)-OOCPh))2(μ-κ(2)-OOCPh)2(μ(2)-OH)2]·Et2O (3·Et2O), [[Cp*ZrCl2](μ-Cl)(μ-OH)(μ-O2CC6H5)[Cp*Zr]]2(μ-O2CC6H5)2 (4), and [Cp*ZrCl4][(Cp*Zr)3(κ2-OOC(C6H4Br)3(μ3-O)(μ2-Cl)2(μ2-OH)] [5](+)[Cp*ZrCl4](-). The structural characterization of the five complexes was carried out. Species 3·Et2O exhibits host-guest properties where the diethyl ether molecule is included in a cavity formed by two carboxylate moieties. The secondary interactions between the cavity and the diethyl ether molecule affect the structural parameters of the complex, as demonstrated be the comparison of the density functional theory models for 3 and 3·Et2O. Species 5 was shown to be isostructural to the [(CpZr)3(μ(3)-O)(μ(2)-OH)3(κO,O,μ(2)-O2C(R))3](+) metallocavitands