Nucleophilic Alkaline Earth Boryls: From Conception and Theory to Application

Lead Research Organisation: University of Bath
Department Name: Chemistry

Abstract

Some of the greatest benefits to human health and well-being have been provided by modern methods of chemical synthesis. Boron compounds provide some of the most widely used reagents in chemistry and are employed in myriad syntheses of pharmaceutical and other high value molecules (e.g. with uses in electronic materials and chemical sensing). Organoborane, boronate ester and boronic acid derivatives, thus, provide some of the most practically useful intermediates in synthetic and medicinal chemistry, to the extent that the application of boron in organic synthesis has been recognised by the award of two Nobel prizes (Brown in 1979 and Suzuki in 2010). Despite these advances, almost all of these compounds are synthesised from starting materials in which boron acts as an electron acceptor (electrophile). This is a natural consequence of boron's position at the top of group 13 in the periodic table and presents a severe limitation to the types and variety of boron compounds that can be made.

In this project we will build on our recent discovery (Nature Commun. 2017, 8, 15022) that derivatives in which boron is bonded to a less electronegative group 2 element, magnesium, are easily generated by activation of the B-B bonds of commercially available diboranes. In contrast to the vast majority of available boron reagents, the boron in these compounds reacts as a potent electron donor (nucleophile), providing the potential to allow the synthesis of a wide variety of new boron-containing molecules. In this project, we will apply a multifaceted inorganic/organic synthetic and computational approach to devise, understand and apply a wide array of new and highly reactive boron derivatives of the group 2 metals, primarily magnesium and calcium. The attractiveness of these latter elements is underscored by their negligible toxicity, high natural abundance and resultant low cost. Furthermore, the boron nucleophiles developed in this project will be used in the synthesis of a plethora of unprecedented and previously inaccessible organic and inorganic boron-containing compounds. Our ultimate objective is to ensure that these reagents are available from commercial chemical suppliers and nothing short of establishing previously inaccessible boron nucleophiles as off-the-shelf reagents in the synthetic chemist's larder.

Planned Impact

Since our initial report of the first molecular (as opposed to macromolecular) catalysis based on an alkaline earth element, the calcium-mediated intramolecular hydroamination of aminoalkenes (J. Am. Chem. Soc. 2005, 127, 2042), the use of complexes of the heavier group 2 elements (Mg, Ca, Sr and Ba) to achieve atom-efficient chemical transformations has become something of a 'hot topic' in contemporary synthetic chemistry. Indeed, the area has been highlighted as such several times in recent review and perspective articles (e.g. Chem Soc. Rev. 2016, 45 (4), pp. 972-988, cited 36 times in 12 months) and was even afforded its own dedicated chapter in the 2013 compendium 'Comprehensive Inorganic Chemistry II' (CIC II, 'Alkaline Earth Chemistry: Applications in Catalysis', 2013, vol 1, Pages 1189-1216, M. Arrowsmith, M.S. Hill). Stimulated by our initial publications, a number of groups across the world have now become active in the area and competition is growing rapidly. It can be deduced, therefore, that our previous work has been highly influential and has provided the highest academic impact. There is no reason to expect that the advances targeted in the current proposal will be any less influential.

In parallel to our research in group 2-based reactivity, the pursuit of boryl anions has stimulated widespread activity as a result of their potential to allow access to a wide variety of boron-containing molecules. The central theme of the proposed research is to exploit the enormous untapped, yet readily accessible, reactivity that may be derived from the concept of heterolytic B-B bond activation at an electrophilic metal centre. The academic impact of the uptake of this hypothesis should be self-evident and would lead the way toward the deliberate design of many main group systems for the routine installation of boron units and the synthesis of valuable B-based molecules when electrophilic boron reagents are inapplicable.

Although our previous work and the research described in this proposal is unashamedly academic, the methods to be devised in this project will undoubtedly influence chemists world-wide; areas as diverse as pharmaceutical synthesis, photocatalysis and the development of novel molecular electronic materials will be enabled through this research. From this perspective, it is highly likely that our research will also attract the attention of industrialists, which is to be facilitated by the 'forum' activities described in the Pathways to Impact document. While the uptake of even one new industrial process over the next 20 years as a direct consequence of the activities of this project would provide a more than tangible economic impact, our ambition is significantly more diverse. Such is the simplicity and flexibility of the synthetic methods described, our ultimate objective should be nothing less than to ensure that these reagents are available to all synthetic chemists from commercial chemical suppliers (e.g. Sigma-Aldrich, Strem) and to establish such previously inaccessible boron nucleophiles as off-the-shelf reagents.

Publications

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Garcia L (2019) Multimetallic Alkaline-Earth Hydride Cations in Organometallics

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Morris LJ (2019) Calcium stannyl formation by organostannane dehydrogenation. in Chemical communications (Cambridge, England)

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Pécharman A (2018) Synthesis of Unsymmetrical Diboranes by Diborane Metathesis in Angewandte Chemie

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Pécharman AF (2018) Diborane heterolysis: breaking and making B-B bonds at magnesium. in Dalton transactions (Cambridge, England : 2003)

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Pécharman AF (2018) Synthesis of Unsymmetrical Diboranes by Diborane Metathesis. in Angewandte Chemie (International ed. in English)

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Pécharman AF (2019) Diborane heterolysis and P(v) reduction by PhP[double bond, length as m-dash]O coordination to magnesium. in Chemical communications (Cambridge, England)