The Reaxys PhD Prize 2019

Mr Michael Geeson
MIT

PhD Supervisor: Prof Christopher Cummins
The Cummins Group

Phosphoric acid as a precursor to chemicals traditionally synthesized from white phosphorus

Geeson, M. B.; Cummins, C. C. Phosphoric Acid as a Precursor to Chemicals Traditionally Synthesized from White Phosphorus. Science 2018, 359 (6382), 1383–1385. https://doi.org/10.1126/science.aar6620.

White phosphorus, generated in the legacy thermal process for phosphate rock upgrading, has long been the key industrial intermediate for the synthesis of phosphorus-containing chemicals, including herbicides, flame-retardants, catalyst ligands, battery electrolytes, pharmaceuticals, and detergents. In contrast, phosphate fertilizers are made on a much larger scale from phosphoric acid, obtained by treating phosphate rock with sulfuric acid. Dehydration of phosphoric acid using sodium chloride gives trimetaphosphate, and here we report that trichlorosilane, primarily used for the production of high-purity silicon, reduces trimetaphosphate to the previously unknown bis(trichlorosilyl)phosphide anion. This anion offers an entry point to value-added organophosphorus chemicals such as primary and secondary alkyl phosphines, and thus to organophosphinates, and can also be used to prepare phosphine gas and the hexafluorophosphate anion, all previously available only downstream from white phosphorus.

Dr Yujia Qing
University of Oxford

PhD Supervisor: Prof Hagan Bayley
Bayley Group

Directional control of a processive molecular hopper

Y. Qing, S. A. Ionescu, G. S. Pulcu, H. Bayley, Directional control of a processive molecular hopper. Science 361, 908–912 (2018).

Intrigued by the potential of nanoscale machines, scientists have long attempted to control molecular motion. We monitored the individual 0.7-nanometer steps of a single molecular hopper as it moved in an electric field along a track in a nanopore controlled by a chemical ratchet. The hopper demonstrated characteristics desired in a moving molecule: defined start and end points, processivity, no chemical fuel requirement, directional motion, and external control. The hopper was readily functionalized to carry cargos. For example, a DNA molecule could be ratcheted along the track in either direction, a prerequisite for nanopore sequencing.

Dr Aaron Trowbridge
University of Cambridge

PhD Supervisor: Profe Matthew J. Gaunt
The Gaunt Group

Multicomponent synthesis of tertiary alkylamines by photocatalytic olefin-hydroaminoalkylation

A. Trowbridge, D. Reich, M. J. Gaunt, Nature 2018, 561, 522 – 527

There is evidence to suggest that increasing the level of saturation (that is, the number of sp3-hybridized carbon atoms) of small molecules can increase their likelihood of success in the drug discovery pipeline. Owing to their favourable physical properties, alkylamines have become ubiquitous among pharmaceutical agents, small-molecule biological probes and pre-clinical candidates. Despite their importance, the synthesis of amines is still dominated by two methods: N-alkylation and carbonyl reductive amination. Therefore, the increasing demand for saturated polar molecules in drug discovery has continued to drive the development of practical catalytic methods for the synthesis of complex alkylamines.

In particular, processes that transform accessible feedstocks into sp3-rich architectures provide a strategic advantage in the synthesis of complex alkylamines. Here we report a multicomponent, reductive photocatalytic technology that combines readily available dialkylamines, carbonyls and alkenes to build architecturally complex and functionally diverse tertiary alkylamines in a single step. This olefin-hydroaminoalkylation process involves a visible-light-mediated reduction of in-situ-generated iminium ions to selectively furnish previously inaccessible alkyl-substituted α-amino radicals, which subsequently react with alkenes to form C(sp3)–C(sp3) bonds. The operationally straightforward reaction exhibits broad functional-group tolerance, facilitates the synthesis of drug-like amines that are not readily accessible by other methods and is amenable to late-stage functionalization applications, making it of interest in areas such as pharmaceutical and agrochemical research.