Thiol additions to acrylates by fluorous mixture synthesis: relative control of elution order in demixing by the fluorous tag and the thiol substituent

All possible combinations of a series of three fluorous benzyl tags and three acrylates have been made. The resulting acrylate esters were combined in groups of three (one of each tag) and the resulting mixtures were reacted with a mixture of four thiols under standard conditions to effect conjugate addition. Analysis of the resulting libraries by fluorous hplc showed a primary separation based on the tag and revealed reliable secondary separations based on the thiol and the acrylate. The primary and secondary separations were used together in a preparative ‘mixture of mixtures’ experiment in which one of the tagged acrylate mixtures was reacted with a mixture of three thiols. The resulting nine component mixture was demixed by fluorous and reverse phase hplc and then detagged to give all nine final products in pure form.