Cleavage Cyclorelease Strategy

Therefore it has to be distinguished from traceless-cleavage. As the intramolecular step is in general faster than any intermolecular step, this strategy provides an additional purification step, because only cychzed structures are detached from the resin. The method of cyclative cleavage by nucleophihc displacement has been 

Since then this method has been used for the development of synthetic strategies for many kinds of heterocycles, such as hydantoins [173, 174] or diketopipera-zines [175] as well as natural products [120] cychc peptides [176] and macrocycUc lactones [108]. 

Besides nucleophilic attack, cyclative cleavage can be eaffected for example by Stille reactions [120], Wittig olefmation reactions [177], Wittig-Horner [178, 179] or metathesis reactions [180-183]. For more details of C-C-bond formation, see Section 3.3.2. 

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In such linkers, the latent bond requires activation before cleavage can occur. Many of the linker units discussed elsewhere in this chapter could be considered safety-catch linker units. For example, photolytic activation described in Section 1.2.4 and cyclorelease discussed in Section 1.2.2 are essentially safety-catch strategies. This section, however, will concentrate on synthetic activation. The first example of such an approach was a sulfonamide linker reported by Kenner et al. in 1971. The sulfonamide 7 is stable to both acidic and basic conditions, making it synthetically valuable. However, alkylation of the nitrogen with, for example, diazomethane or iodoacetonitrile, gave 8, from which substrates (e.g., carboxylic acids 9) could be cleaved under nucleophilic conditions (Scheme 1.4). 

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