Solid-Phase-Bound Reagents

Auxiliary reagents, or products derived from them (e.g., tertiary amines or coupling reagents) are one of the most common sources of impurities. Adding such reagents bound to solid support provides a very efficient way of avoiding such impurities (Table 3.11). 

Reaction Reagent Presence of other functional groups Reference 

Wittig olefination with aliphatic and aromatic aldehydes and ketones diphenylphosphine derivatized polystyrene [129] 

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Of great help in solution chemistry is are presented by solid-phase- bound reagents, which can be removed after reaction by a simple filtration process. The great potential of this approach has recently been demonstrated in a total synthesis of epothilones applying only solid- phase-bound reagents. 

Solid-phase-bound reagents have also been used for precipitating excess reagents so that they may be removed by simple filtration. As an example, a combination of a resin-bound calcium sulfonate and a sulfonic acid resin is able to remove excess TBAF from silyl deprotection reactions. This treatment precipitates the fluoride as CaF2 whereas the tetrabutylammonium remains bound to the sulfonic acid resin [139]. 

One problem that may be encountered with this type of reaction is related to the fact that in solid-phase synthesis reagents generally have to be used in excess. This can occasionally lead to side reactions, ff, for instance, a resin-bound aldehyde is condensed under basic conditions with excess ketone, the resulting enone might undergo Michael addition with an additional equivalent of ketone (Figure 5.10). For some of these enones, the Wittig reaction may represent a superior synthetic method [75]. 

Lanthanide labelled antibodies or antigens, can be applied to most assays based on solid-phase separation. Reagents immobilized to microtitration plates allow an easy and efficient separation of the unbound fraction by using a plate washer. The bound fraction of the labelled gagent is quantified with a specially designed time-resolved fluorometer (DELFIA Research Fluorometer, Victor Multilabel Counter, Wallac Oy, Turku, Finland). 

As indicated, ELISAs involve the stepwise addition and reaction of reagents to a solid phase-bound substance, through incubation and separation of bound and free reagents using washing steps. 

Solid-phase techniques are also used for synthesis of compounds with trans-decalin motif where the Robinson annulation is used for synthesis of some natural product inspired structures such as that of 75. The protocol uses an immobilized solid phase bound Nazarov reagent that reacts with the enamine of the starting ketone under basic conditions. After cyclization the product is released from the solid phase by using TBAF at room temperature overnight. For the products 75a-c only one stereoisomer was formed (de > 98%) with modest 22-38% yields. 

Although an enantioselective reaction carried out on solid phase, in principle, also includes the reactions wherein a chiral catalyst or a chiral auxiliary is polymer bound, in this chapter we have mainly focused on reactions wherein a substrate is bound to a solid support and the chemical transformation is carried out by chiral reagents. However, we have included few examples of employing solid-supported catalyst and auxiliaries to give readers an idea of these alternative synthesis strategies. Readers are, however, advised to refer to Refs 6 and 7 for a review on the applications of immobilized chiral catalysts and solid-phase-bound chiral auxiliaries, respectively, and Refs 1,5, and 8 for diverse solid-phase synthesis approaches directed toward small molecules and natural products. ... 

Four types of techniques for separating the bound fraction P Q from the reagent mixture are in common usage, loosely termed double antibody, solid phase, charcoal adsorption and solution precipitation. The first type is used with radioimmunoassay methods specifically, while the other three types can be used with both radioassay and radioimmunoassay methods. 

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

In 1983, Prasad et al.12 first reported the condensation of chloromethyl polystyrene with /V-hydroxyphthalimide to give the ester, hydrazinolysis of which yielded the desired resin-bound hydroxylamine. However, the sole purpose of this reagent was to react with, and hence extract ketones from, a complex steroidal mixture, and its use for the solid-phase synthesis of hydroxamic acids was not explored. Recently, the exploitation of the above solid-phase approach for the synthesis of hydroxamic acids was independently reported by three groups,7-9 all of which differ only in the method for the initial anchoring of TV-hydroxyphtha-limide to an 4-alkoxybenzyl alcohol functionalized polystyrene or trityl chloride polystyrene. Subsequent /V-deprotection was... 

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