Fluorous synthesis with fewer fluorines (light fluorous synthesis): separation of tagged from untagged products by solid-phase extraction with fluorous reverse-phase silica gel

Fluorous synthesis involves tagging an organic substrate with a fluorinated tag for the purposes of separation. To date, techniques of fluorous synthe sis have relied on liquid-liquid extractions. This paper applies a simple s olid-liquid extraction procedure over fluorous reverse-phase silica gel (si lica with a fluorocarbon bonded phase) for use in fluorous synthesis. Four amino acids were tagged on nitrogen with the C9F19CO-group, and the resulti ng acids were coupled in a parallel experiment with an excess of four amine s. The resulting 16 crude fluorous amide products were separated from all t he coupling reagents and excess amine by twostage filtration through fluoro us silica. In 15 of the 16 cases, the products were isolated in good to exc ellent yield and purity. All of the products are soluble in organic solvent s and none is expected to have any significant solubility in fluorous solve nts, so the experiment dramatically illustrates the advantages of the solid -liquid extraction over the liquid-liquid extraction. Future prospects for application of fluorous silica are briefly discussed.