Nucleoside analogues are an important class of pharmaceutical agent showing activity towards a range of biological targets. For therapeutic applications nucleosides are typically modified at a variety of different positions including the ribose sugar, the phosphate backbone or the nucleobase, depending on the desired pharmacological properties 2 . Particularly important and synthetically challenging is the 2′-modification of the ribose sugar, being utilized in both nucleoside analogue drugs (Figure ), and also nucleoside building blocks of therapeutic oligonucleotides (Figure ). Therapeutic oligonucleotides are an important new modality that facilitate a precision medicine approach for patients. Modifications to the 2'-position of the nucleoside, e.g. 2′-methoxy, 2′-methoxyethoxy (MOE), and 2′fluoro are all commonly deployed substitutions in therapeutic oligonucleotides (Figure ) which impart both resistance to nucleases and improvements in RNA binding affinity.