Cyclorelease Linker Units

Pavia s linker unit exploits amide or urea bond formation with concomitant displacement of the solid support, which is by far the most common approach for achieving cyclative cleavage. The first example of such an approach was Marshall s preparation of cyclic dipeptides, as shown in Table 1.3, Entry 1. Besides this, such classical cyclization C—N bond forming reactions have been used to prepare ambitious synthetic targets using SPOS, 

LINKER STRATEGIES IN MODERN SOLID-PHASE ORGANIC SYNTHESIS 

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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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