Recently, we published a paper about gravity-driven FSPE (J. Combi. Chem. 2007, 9, 836-843). In all previous fluorous solid phase extraction applications using FluoroFlash® silica gel, positive or negative pressure is required or otherwise the process would take too long. It’s also more difficult to apply a positive or negative pressure driven process to a multi-well plate, since not all of the wells will flow similarly. So while the normal FluoroFlash® systems are great for singles or small libraries, something else is needed for bigger libraries. In this publication, we used a larger particle size (125-210 micron) fluorous silica gel which allowed flow rates large enough for gravity FSPE. The gravity FSPE was then applied to plate-to-plate purification for parallel synthesis. Up to 50 mg of reaction mixture can be loaded onto each well. The fluorophobic wash with DMSO, DMF, or 85:15 DMF-H2O elutes organic compounds while fluorous compounds remain on the silica gel. This simple and highly efficient plate-to-plate F-SPE technique has been demonstrated in the purification of four 96-compound libraries produced by scavenging reactions with fluorous isatoic anhydride, amide coupling reactions with Fluorous CDMT or Fluorous DCT, and Mitsunobu reactions with F-DIAD and F-TPP. Approximately 80% of products in each library have greater than 85% purity after F-SPE without conducting chromatography. It is also noteworthy that water-free elution with DMSO and DMF was demonstrated in the paper.
We feel this newly developed F-SPE technology is an important complement to previously developed vacuum-driven and positive pressure-driven FSPE technologies and products (Tetrahedron 2006, 62, 11837; J. Combi. Chem. 2005, 7, 893; J. Combi. Chem. 2006, 8, 890).