Mapping the chemistry of phosphorus-containing analogues of urea. From fundamental chemistry to high-performance compounds and materials.

The isolobal analogy is frequently invoked to draw comparisons between the fundamental chemistry of small inorganic molecules and more established organic species. For example, the diagonal relationship between a methine fragment (C-H) and phosphorous has led to the latter being nicknamed a "carbon-copy". This has resulted in extensive chemistry aimed at developing phosphorus-containing analogues of organic molecules such as phospha-alkenes (RP=PR) and -alkynes (PCR), amongst many other examples. However, an isolobal relationship does not imply that phosphorus-containing congeners of specific organic molecules can be readily synthesized. In fact, the synthesis of relatively simple molecules where a C-H unit, or even an isoelectronic element such as nitrogen, has been replaced by a phosphorus atom still represents a significant technical and intellectual challenge. In this regard synthetic inorganic chemistry lags far behind organic synthesis.

As a case in point, while urea was first synthetically isolated in 1829, it was not until late 2013 that our research group succeeded in the isolation of a phosphorus analogue, phosphinecarboxamide. Considering the importance of urea as a chemical feedstock, we propose to utilize this heavier analogue (and other related species) for the synthesis of novel molecules and solids. This is a completely new approach to organophosphorus compounds which, while inherently risky, has the potential to generate fascinating new species that are related to those derived from urea, but that have fundamentally different chemical and physical properties.

Current methods for the synthesis of phosphorus-containing chemicals (employed, for example, in pharmaceuticals and specialty chemicals such as photo-initiators) require the use of phosphorus (III) chloride as a feedstock. While such processes currently represent the industrial state-of-the-art, the use of alternative non-toxic precursors remains a highly desirable objective. Alternative strategies to organophosphorus compounds based on the chemical activation of white phosphorus are possible (and well-documented in the literature), however such transformations are often marred by low selectivities or require multiple subsequent manipulations to be competitive with industrial processes. Moreover, white phosphorus is itself highly pyrophoric and dangerous to manipulate. The risks associated with these precursors make the identification of novel phosphorus-atom feedstocks highly desirable.

We propose to develop the chemistry of a new class of phosphorus-containing small molecules that are accessible using red phosphorus, a non-pyrophoric allotrope of the element. Ultimately, this will allow us to reduce the safety risks typically encountered when manipulating conventional precursors for the synthesis of specialty chemicals. Building on recent breakthroughs in our laboratory, we will explore the chemistry of the 2-phosphaethynolate anion and phosphinecarboxamide, two novel phosphorus-containing analogues of otherwise ubiquitous chemicals (the cyanate ion and urea, respectively). Our ultimate goal is to access novel molecular, supramolecular and polymeric species with potential applications in catalysis, chemical sensing and materials chemistry. This proposal represents an entirely novel approach to the development of phosphorus-containing molecules and solids of enormous potential societal and economic impact.

The main goal of this proposal is to generate a new family of main-group compounds with potential applications as supporting ligands and/or precursors to novel inorganic materials. Developing an understanding of the fundamental reactivity of the 2-phosphaethynolate anion will allow us to access species that have eluded chemists for decades and to target unprecedented compounds. Total synthesis of complex organic molecules is possible due to our current understanding of reaction mechanisms - a knowledge pool that has been developed over centuries. However, the identification of target molecules containing the heavier inorganic elements is significantly more challenging. At present, the design and synthesis of relatively simple molecules containing, for example, elements of group 15, poses a significant difficulty, in large part due to our lack of understanding of fundamental chemical reactions and their mechanisms. We aim to develop this area by expanding the precursor palette available to synthetic chemists. These fundamental breakthroughs will have a long-lasting and transformative impact on the fields listed below.

Academic: We are in a position to develop an entirely new area of main-group chemistry, which will allow us to generate molecules that can be used for further stoichiometric and catalytic processes. The results of this research programme will be published in high-impact peer-reviewed journals with a global readership (Nature Chem., J. Am. Chem. Soc., Angew. Chem. Int. Ed. etc.) and disseminated at leading international conferences. A strong emphasis will be placed on building national and international networks with researchers in the U.K. and abroad.

Health and safety: The reagents we propose to study can be accessed using red phosphorus as a precursor (which is less dangerous than other species conventionally employed in the synthesis of organophosphorus compounds). Replacing phosphorus trihalides and white phosphorus for red phosphorus in small and medium scale transformations of specialty chemicals promises to be truly transformative. While the use of white phosphorus will never be fully circumvented, replacing its use at the laboratory scale for bespoke chemical transformations has true value, particularly as health and safety regulations become more stringent.

Financial: The ultimate objective of this proposal is to access novel phosphine ligands and polymeric inorganic materials. With regard to the former species, we are in a position to transform a plethora of terminal amines into novel phosphines. In homogeneous catalysis, the choice of supporting ligands is critical in order to influence catalyst activity and stability. Ligand design is a crucial aspect of catalyst development, and arguably no family of ligands has been used more extensively in catalysis than phosphines. Our research has the potential to deliver hundreds of novel ligands including value-added species such as chiral phosphines, small bite angle and bidentate ligands, high denticity species and others.

Furthermore, we also have access to a family of compounds that can be employed for the synthesis of novel inorganic polymers. By comparison with organic polymer chemistry, the field of inorganic polymers (i.e. materials containing elements other that C and H) is largely underdeveloped. We propose to access three novel types of phosphorus-containing polymers with properties that make them highly desirable due to their unique properties (e.g. as flame-retardants and toxic metal ion sequestering agents).

Staff development: This research will allow the PDRA to develop crucial analytical, experimental and inter-personal skills which will equip them to become a future research leader. At the same time it will permit the PI to consolidate his reputation as a leading figure in molecular inorganic chemistry and facilitate the attainment of future research funding from national, European and international sources.