Utilising a novel Ni/Zn catalytic system in small molecule synthesis

Mala, Bara and Doulcet, Julien and Sweeney, Joe (2022) Utilising a novel Ni/Zn catalytic system in small molecule synthesis. PhD thesis, Lancaster University.

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Abstract

Transition metals have been used in C–C bond forming reactions for many decades. The use of palladium-based catalysts has dramatically increased in the last few years, however, there is a growing industrial need for low-cost, more abundant metals in catalysis. Nickel is often used as a replacement for palladium, as it is capable of catalysing many of the same reactions, whilst being significantly cheaper and more readily available. The most widely used Ni-catalyst, Ni(cod)2, requires handling in a glove box, and although some catalytic systems employ airstable pre-catalysts, these often require multiple step synthesis or an excess of reducing agents, making these reactions unfavourable for industrial scale up. This work explored the application and robustness of a simple, novel Ni-based catalytic system to reactions that have previously utilised either Pd-based catalysts or Ni(cod)2. The catalytic system described here comprises of a commercially available nickel salt (NiBr2.3H2O) and sub-stoichiometric amounts of zinc as the reducing agent. Utilising this system could ultimately allow for an easily scalable, and inexpensive benchtop synthesis. Here this Ni/Zn catalytic system is used to successfully catalyse the direct allylation of simple ketones with allyl alcohols in the presence of pyrrolidine as a co-catalyst. Substitution of the co-catalyst for a chiral pyrrolidine allowed for enantioselective allylation of ketones without the need for intricate chiral ligands. The system also successfully catalysed the allylation of branched aldehydes with allyl alcohols, although with a smaller substrate scope. Interestingly, this reaction did not require the use of a co-catalyst, highlighting the need to further explore the mechanism of this Ni/Zn system to fully understand and appreciate its potential.