Cleavage Yielding Primary and Secondary Amides

The formation of amides from resin-bound esters is besides cleavage to give carboxylic acids/esters the most used cleavage procedure. 

Because of the relation between hnker structure and aminolysis sta-bihty of the ester hnkers, a lot of—more or less similar—ester linkers have been developed to reach easy release and compatibihty with all reaction steps (Fig. 6, [101-109]). Some stabihty data for selected nucleophiles are available stabihties towards morpholine for example reach from resins with half-hfe times of 0.17 h to resins with half-life times of 50 h and more [110]. 

To overcome these problems some safety-catch hnkers were developed by the groups of, for example, Merrifield [111], Cowell and Jones [112] as well as Main [110]. All studied o-hydroxy-phenyl esters because of their moderate stabihty concerning reactions with nucleophiles in their protected form and because of their low stabihty towards nucleophiles in the unprotected form (phenol-derivatives). These researches confirm former results describing on the one hand low reactivity concerning sterically hindered ester hnkers and on the other hand high reactivity for arylesters bearing an 0-hydroxy-substituent that supports nucleophilic cleavage via anchimeric as- 

There are some thioesters that can be used for release of amides via aminolysis developed by Vlattas et al. in 1997 (Fig. 7) [90]. 

Thioester 84 has been used for aminolysis by several primary amines (beyond that it was used for Grignard addition) to give the corresponding amides in non-hydroxyUc solvents such as dioxane with 70-80% yield. For reaction of secondary amines with thioesters, more reactive thioesters like 82 and 83 were needed. 

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