Ionic liquids can provide an excellent medium for the preparation of highly air and moisture sensitive chlorophosphoramidite reagents. As an extension to this, the use of these ionic liquid stabilised materials as phosphitylating reagents has been explored. Initially a biphasic ionic liquid-solvent system was investigated, however the enhanced solubility of the chlorophosphoramidites and the limited solubility of partially protected nucleosides and 2-deoxynucleosides in ionic liquids gave rise to a set of conditions that limited the scope of these reactions. What was required was to either reduce the solubility of the chlorophosphoramidite reagents or enhance the solubility of the nucleosides in the stabilising medium. It is known that liquid assisted mechanochemistry can be used to enhance the solubility of materials when used in combination with a suitable solvent.To this end liquid assisted mechanochemistry using a range of ionic liquids stabilised chlorophosphoramidite reagents to phosphitylate nucleosides and 2-deoxynucleosides has been investigated. We show that the enhanced stability offered by the ionic liquid mediated process combined with efficient mass transfer induced by ball milling has enabled excellent yields to be obtained even when using chlorophosphoramidite reagents with small, highly-sensitive dialkyl amino groups, as well as the more commonly used diisopropylamino subtituents for protection.

Liquid assisted mechanochemistry for the phosphitylation of nucleosides using ionic liquid stabilised reagents

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.