Resin support scavenger

Application of Polystyrene Resin-Supported Scavengers towards the Synthesis of Natural Products... 

Scheme 2.57 Three component condensation reaction using polymer supported scavenger purification alternatively the trisamine resin could be substituted for purification in this step.

The concept of selective sequestration of non-product species was first demonstrated using solid-supported scavengers with electrophilic and nucleophilic character in amine acylation, amine alkylation, and reductive amination protocols [46]. Since then, a wide range of scavenger reagents has become commercially available from various suppliers. The structures and functions of these scavenger resins are shown in Table 1. 

Since the discovery of solid phase peptide synthesis in 1963 [4], the venerable polystyrene resin has remained the cornerstone of combinatorial chemistry over the years and continues to be utilized as the primary mode of support for immobilizing reagents and scavengers. This section briefly outlines the latest developments of resin-based scavengers. 

Fontaine and coworkers have recently reported the synthesis of a supported aza-lactone via atom radical transfer polymerization (ATRP) [9]. This method involved the preparation of a Wang resin-supported initiator, followed by subsequent ATR polymerization between 2-vinyl-4,4-dimethyl-5-oxazolone (VAZ) and styrene to generate several macroporous, aza-lactone functionalized resins with different architectures. These were shown to scavenge benzyl amines in a highly efficient fashion (Scheme 8.5). 

Maleimide is a well-known Michael acceptor, dienophile and dipolarophile and hence is another versatile functional moiety that has found multiple uses in combinatorial chemistry as both a scavenger as well as a template in library synthesis [15]. Barrett [16] and Porco [17] have both reported the synthesis of a polystyrene resin-supported maleimide but did not report its use in the scavenging of nucleophiles. Hall and coworkers have described the synthesis of a supported-maleimide... 

Coupled with the fact that the proportion of trace metal contaminants detected within continuous flow reaction products is inherently low, due to reduced catalyst degradation, the use of a scavenger cartridge at the end of a reaction sequence represents a relatively long-term solution to this problem. Other examples of the use of solid-supported scavengers have been reported by Ley and co-workers [65], where in one example, two scavenger modules, comprising QuadraPure TU (126) and phosphane resin, were used in the synthesis of 1,4-disubstituted-l,2,3-triazoles [66], and by Watts and co-workers [67], where silica-supported copper sulfate was used for the removal of residual dithiol (ppb) in the synthesis of 1,3-dithiolanes and 1,3-dithianes. 

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

---