ROMPgel beads in IRORI format: acylations revisited

Functionalized "designer" polymers derived from ring-opening metathesis polymerization (ROMPgels) are attractive for their high loading, high purity, and ease of synthesis. Their physical state may vary from liquid to gel to granular solid, making a general method of handling these polymers difficult. By incorporating a suitable norbornene-substituted linker on standard Wang beads, ROMPgels can be easily grafted onto the resin, adding the convenience of a bead format while still maintaining the high loading and excellent site accessibility. This advantage is demonstrated by the use of an N-hydroxysuccinimide ROMPgel (3.3 mmol g(-1), a 3-fold increase from the parent linker resin) in IRORI Kan format. Conditions for the acylation of these IRORI-formatted ROMPgels are reported, along with the scope and limitations of the choice of acylating reagents. Yields are greatly improved by the use of perfluorinated solvents as a nonparticipating cosolvent in the acylation process. A simple titration method for the quantification of the acylated ROMPgels is also reported. Spent Kans are regenerated after each use without apparent loss of activity or purity after several cycles. Due to the high loading and reduced swelling of the ROMPgel resin, up to 0.39 mmol acyl group has successfully been recovered from a single IRORI miniKan, demonstrating the high capacity of the resin and applicability to both lead discovery and optimization programs.