Exploring alternative phosphorus and heavier pnictogen feedstocks for bespoke chemical transformations

The chemical activation of white phosphorus by transition-metal and main-group element complexes has historically been heralded as a way of circumventing the use of phosphorus trichloride as a chemical feedstock. Despite its toxic nature (and the fact that its use is currently regulated under the Chemical Weapons Convention), phosphorus (III) chloride remains the principal P-atom source for all of the organophosphorus compounds we encounter on a daily basis in detergents, pharmaceuticals and specialty chemicals. At present, pre-existing technological investment and cost issues make it unfeasible to employ alternative methods for the production of bulk phosphorus-containing chemical commodities. However, the use of alternate feedstocks for the synthesis of value-added specialty chemicals is very attractive both financially and from a health and safety perspective. The direct chemical activation of white phosphorus is demonstrably a viable route to organophosphorus compounds; unfortunately such transformations typically exhibit low selectivities and/or require multiple subsequent manipulations to be competitive with industrial processes. Furthermore, white phosphorus is itself highly pyrophoric and a dangerous substance to manipulate (notoriously used throughout history as a chemical weapon). Nonetheless, throughout the last forty years the chemical activation of white phosphorus has generated an incredibly rich and diverse area of fundamental chemistry (fields such "phospha-organic" and "inorganometallic" chemistry have blossomed as a result) allowing the scientific community to develop transformative concepts that have had repercussions in fields ranging from supra-molecular chemistry to catalysis.

We propose to investigate alternative group 15 element (P, As, Sb, Bi) feedstocks for the synthesis of novel organo-pnictogen compounds. Preliminary proof-of-concept findings by our research group have demonstrated that binary Zintl phases of the alkali metals and group 15 elements may be used as starting materials for the synthesis of novel species containing pnictogen analogues of organic ligands (these transformations are closely related to metal-mediated processes for the activation of white phosphorus). Moreover, we have also shown it is possible to use such species for the direct chemical activation of small molecules such as alkynes. It is important to note that these salt-like Zintl phase precursors can be accessed using safer allotropes of the group 15 elements (red phosphorus, metallic grey arsenic), thus avoiding the risks associated with the manipulation white phosphorus or yellow arsenic. This makes the manipulation of such species notably less dangerous, reducing the health and safety risks typically encountered when manipulating more traditional feedstocks (while Zintl phases are still air- and moisture-sensitive they are do not spontaneously combust on contact with air). We propose to investigate the reactivity of Zintl phases towards a library of low-valent transition-metal and small molecule reagents with the aim of synthesizing otherwise unattainable "pnicto-organic" molecular species. Our strategy towards such compounds centres on two complimentary synthetic methodologies: 1) the metal-mediated activation of anionic pnictide cages with low-valent transition-metal complexes; and 2) the direct reaction of pnictide polyanions with unsaturated small molecule substrates. Ultimately, we believe such studies will give rise to novel molecular species of the group 15 elements that may be used - directly or as supporting ligands - in stoichiometric and catalytic bond activation processes or as precursors to novel materials.

The main objective of this proposal is to generate an entirely new area of molecular main-group chemistry centred on the use of anionic cages of the group 15 elements as precursors to novel compounds. This research will strongly complement the numerous invaluable studies that have been carried out to date on the chemical activation of white phosphorus (and to a much lesser extent yellow arsenic). Developing an understanding of the reactivity of anionic polypnictide cages will allow us to access molecular species that have eluded chemists for decades and to target unprecedented new compounds. Total synthesis in organic chemistry is a possibility due to an extensive fundamental understanding of reaction mechanisms developed over centuries. A similar goal, to identify a complex target molecule and devise a method of synthesizing such a species, is much more elusive for inorganic chemists. At present the design and synthesis of relatively simple molecules containing, for example, elements of group 15 can be quite challenging, in large part due to our lack of understanding of fundamental chemical reactions and their mechanisms. We aim to help develop this area by expanding the synthetic precursor palette available to chemists. These fundamental breakthroughs will have long-lasting and transformative impact in the fields listed below.

Academic: We are in a position to develop an entirely new area of main-group chemistry generating molecules that can be used for further stoichiometric and catalytic processes as active species and ligands. See Academic Beneficiaries section.

Health and safety: The precursor compounds we will study can be accessed using less dangerous allotropes of conventional pnictogen atom feedstocks. Replacing white phosphorus for the much less reactive red allotrope in small and medium scale transformations of specialty chemicals promises to be truly transformative, avoiding many of the well-known risks associated with the manipulation of pyrophoric substances. While the use of white phosphorus will never be fully avoided (industrially the red allotrope is derived from white phosphorus), replacing its use at the laboratory scale for bespoke chemical transformations has true value, particularly as health and safety regulations become more stringent.

Financial: Among the species we propose to target are compounds based on the group 15 elements capable of activating small molecules either stoichiometrically or catalytically. The use of main-group compounds to activate small molecule regents is an area of research that is receiving enormous attention. The prospect of avoiding the use of precious metal reagents for catalysis is both financially and environmentally attractive. Furthermore, we have also devised a way to target chiral supporting ligands to be used in conjunction with precious metal catalysts. We believe to have identified an inexpensive and versatile route to chiral ligands based on the group 15 elements. If successful this aspect of the proposal promises to have the greatest financial impact as such chiral species often require costly and laborious syntheses.

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 allow the PI to consolidate his reputation as a leading figure in molecular main-group chemistry and facilitate the attainment of future research funding from national, European and international sources.

The results of this research programme will be published in high-impact peer-reviewed journals with a global readership (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.