From lubricants to agrochemicals, ether linkages are important motifs in chemical entities throughout all chemical sectors. The most common method to form ethers is via the Williamson method, a simple and reliable method utilising a metal hydride and an alkylating agent. However, safety issues associated with the reagents and the large amount of inorganic waste products render this methodology undesirable for large scale applications. In recent years, catalytic reductive etherification of carbonyl compounds in the presence of hydrogen gas and various alcohols, to afford the corresponding ether product, has been reported.1 Industrially, catalytic reductive etherification has been developed further by BP Castrol to produce biomass-based automotive lubricants.2 Conversely, the same reaction class has seen much lower application within the pharmaceutical industry, despite its potential to be greener than other etherification methods. This lack of uptake may be attributed to the reported reduction of aromatic substrates under the reaction conditions as well as the use of custom-made catalysts.1 Through use of high-throughput hydrogenation equipment, extensive screening and emerging kinetic studies, a catalytic and industrially viable system has been identified for reductive etherification. These ongoing studies have enabled comparable performance to literature precedent. From the established proof-of-concept, further investigation has been focussed on developing a full and structured understanding of the reaction parameters that affect the efficacy and scope of catalytic reductive etherification.

Reductive etherification

2019 Fall National Meeting

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