Activation of Alcohols for Photochemistry Methodology in the Scalable Hetero-Difunctionalization of Alkenes

Authors: Huaibo Zhao, Dario Filippini, Yiding Chen, Albert Gallego-Gamo, Louise S. Natrajan, Loïc R. E. Pantaine, Ciro Romano & David J. Procter

Pharmaron is delighted to share a recent high impact collaborative publication in Nature Chemistry with Professor David Procter and his group at the University of Manchester.

The Procter group proposed a novel photochemistry methodology to efficiently synthesize 1,2-diols and 1,2-amino alcohols from olefins. 1,2-diols and 1,2-amino alcohols are widely represented in bioactive natural products, as well as in pharmaceutical drugs and agrochemicals.

However, their direct formation from olefins is only possible if one of the pair can be rendered electron-deficient through derivatization; such approaches typically require stoichiometric amounts of strong oxidants and often lack versatility. The development of alkoxide sulfonium salts allows easy access to alkoxide radical under photochemical conditions, unlocking the desired reactivity towards electron rich alkenes.

The Pharmaron team in Hoddesdon, UK, supported industrialising this novel methodology with significant attention devoted to scalability — an essential consideration in the chemical industry. The team adapted the synthesis of the sulfonium starting material to eliminate column chromatography purification in favour of crystallisation, and optimized reaction temperatures that avoided cryogenic conditions.

Further adjustments were made in solvents and reagents selection to successfully streamline the required starting material manufacturing process, allowing the synthesis of 1 kg of material to be feasibly carried out in a 5L vessel. The photochemical process was adapted from a batch to a flow reaction to ensure the scalability of the process, avoiding well-known issues such as light efficiency.

Finally, the laboratory scale photoflow process was transferred to an industrial, kilogram scale using Pharmaron’s bespoke photoflow system to achieve the synthesis of the chosen model substrate in 64% yield over 3.5 h.

Nature Chemistry 2025, November 26

DOI: /10.1038/s41557-025-02003-7

Access the publication at https://www.nature.com/articles/s41557-025-02003-7#