biostudies-literatureXu SNIGMS NIH HHSU.S. Department of Health & Human Services | National Institutes of Health1459-1469https://www.ebi.ac.uk/biostudies/studies/S-EPMC9772297biostudies-literatureUnknown14(12)Molecules that contain one or more fluorine atoms are crucial to drug discovery. There are protocols available for the selective synthesis of different organofluorine compounds, including those with a fluoro-substituted or a trifluoromethyl-substituted stereogenic carbon centre. However, approaches for synthesizing compounds with a trifluoromethyl- and fluoro-substituent stereogenic carbon centre are far less common. This potentially impactful set of molecules thus remains severely underdeveloped. Here we introduce a catalytic regio-, diastereo- and enantioselective strategy for the preparation of homoallylic alcohols bearing a stereogenic carbon centre bound to a trifluoromethyl group and a fluorine atom. The process, which involves a polyfluoroallyl boronate and is catalysed by an in sitNature chemistryDiastereo- and enantioselective synthesis of compounds with a trifluoromethyl- and fluoro-substituted carbon centre.PMC9772297R35 GM128779GM-130395R35 GM130395GM-128779Hu SRomiti FLee JLiu PFu YLee KLi XDel Pozo JMorrison RJMai BKXu SHoveyda AHKoh MJfalseDiastereo- and enantioselective synthesis of compounds with a trifluoromethyl- and fluoro-substituted carbon centre.Molecules that contain one or more fluorine atoms are crucial to drug discovery. There are protocols available for the selective synthesis of different organofluorine compounds, including those with a fluoro-substituted or a trifluoromethyl-substituted stereogenic carbon centre. However, approaches for synthesizing compounds with a trifluoromethyl- and fluoro-substituent stereogenic carbon centre are far less common. This potentially impactful set of molecules thus remains severely underdeveloped. Here we introduce a catalytic regio-, diastereo- and enantioselective strategy for the preparation of homoallylic alcohols bearing a stereogenic carbon centre bound to a trifluoromethyl group and a fluorine atom. The process, which involves a polyfluoroallyl boronate and is catalysed by an in sit2022-01-01T00:00:00Z2022 Dec2025-04-04T09:14:21.139Z2025-04-04T09:14:21.139ZS-EPMC97722973637638710.1038/s41557-022-01054-4