Throughput is a major concern for anyone trying to prepare even small libraries of compounds and a number of tools have been developed to help in making parallel synthesis faster and easier. When coupling two components together, you’ll generally use an excess of the cheaper component in order to drive the reaction to completion. This is especially true in the context of a parallel synthesis effort where you don’t have time to optimize any individual reaction. The downside of using excess reagent is that you have to get rid of it at the end of the reaction. A common procedure is to add an immobilized scavenger to react with excess reagent and allow for easy separation by filtration. The most common solid support used today is polystyrene (PS), and there are a number of commercially available functionalized PS resins out there.
There are a few downsides with these of scavengers, though, that are inherent in the type of support used. First of all, because they’re made from PS beads that are surface-modified, the bulk of the weight is non-functional. In addition, scavenging reactions that occur on the surface of PS are often considerably slower than the corresponding solution-phase processes.
Paul Hanson and coworkers have developed a series of scavengers that overcome some of the limitations of traditional immobilized reagents. In a recent paper,1 they describe the preparation and use of an oligomeric primary amine scavenging reagent. A functionalized norbornene was made by straightforward Diels-Alder chemistry, and ring opening metathesis polymerization using the second generation Grubbs catalyst provided the reagent.
Since each monomer unit contained an amine, the oligomeric amine reagent had considerably more “active” content than similarly available reagents (8.3 mmol/g vs 1.5 mmol/g for PS-NH2). Hanson demonstrated that his oligomeric amines were useful scavengers for acid chlorides, benzyl chlorides, sulfonyl chlorides, and aldehydes. In a typical procedure, 2 equiv. of an acid chloride and 3.1 equiv. of NEt3 were added to 1 equiv. of an amine in CH2Cl2. Upon completion, the oligomeric scavenger (1.5 equiv.) was added and allowed to stir for two hours, then the mixture was filtered through a silica gel plug to give >95% pure material.
1Stoianova, D. S.; Yao, L.; Rolfe, A.; Samarakoon, T.; Hanson, P. R. Tetrahedron Lett. 2008, 49, 4553-4555.