Nitrogen Linker Units

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). 

More recently. Erase has also introduced the T2 triazene linker unit. The T2 linkers are most commonly used for immobilization of amines (and other nitrogenous compounds). As their T1 counterparts, the T2 linkers have also proven robust linkers for SPOS. For example, amines can be cleaved by treating with TFA (Table 1.8, Entry 1), while treatment with trimethylsilyl chloride is typically used when preparing (and cleaving) ureas (Table 1.8, Entry 2) or amides (Table 1.8, Entry 3). Alternatively, the T2 linker can also behave as a photolabile linker unit and photolytic cleavage (X, = 355 nm) by Enders et al. was used as a strategy to release amines (Table 1.8, Entry 4). ... 

Benzotriazole Linker Units. The final class of nitrogen-based linker units... 

Cyclization can also be performed via nucleophilic attack of nitrogen nucleophiles as shown for the release of cyclic urea derivatives. Dressman et al. examined a methodology to cleave hydantoins 222 via treatment of carbamate linkers with an intramolecular amide functionahty and base [188]. In the case of resin-bound substrate 221 (Scheme 33), the resulting heterocycle is a five-membered ring system but other heterocycles containing a urea-type unit can also be synthesized as published by diverse other groups (c.f. benzimidazolone-synthesis of li et al. [199]). 

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