Triazene Linker Units

1 Triazene Linker Units. Owing to their multifunctionality and high stability, triazene linker units have become the most versatile diversity linker units reported to date. Initial reports of triazene linker units appeared in the mid-1990s from the groups of both Moore and Tour. Inspired by this work, the chemistry has been refined by Erase, whose T1 and T2 triazene linker units have now been extensively developed for multifunctional cleavage. 

The T1 linker originally found use as a traceless linker since treatment of T1 resin-bound substrates with TFA was found to release the corresponding aryl diazonium salts. Enders, in his preparation of p-lactams, was then able to show that heating the diazonium salts liberated nitrogen and a hydrogen residue was left at the cleavage site (Table 1.7, Entry 1). In related 

LINKER STRATEGIES IN MODERN SOLID-PHASE ORGANIC SYNTHESIS 

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).  

Treatment of the T2 linker-bound substrates with electrophiles (e.g., MeaSiCl HOAc, TFA, RSO3H) allows inclusion of an additional point of diversity upon cleavage (Table 1.8, Entry 5). The mechanism proposed for such cleavage by Erase is that the diazonium species is initially cleaved, and then displacement of nitrogen from the intermediate by the counterion (Cl , AcO , etc.) provides the products. Typically, a mixture of products is obtained using this cleavage strategy. 

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TABLE 1.7. Cleavage from the Triazene T1 Linker Units... 

TABLE 1.8. Cleavage from the Triazene T2 Linker Unit... 

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