Resin-Supported Diazonium Salts

Esters, which have no possible site of attachment, cannot be directly linked to supports, but may be generated upon cleavage from a support. This cleavage can be mediated by electrophiles, nucleophiles, or oxidants. Only a few examples have been reported of the preparation of esters by O-alkylation of carboxylates by resin-bound alkylating agents, such as sulfonic esters [369-372] or diazonium salts [373] (see also Section 3.13). 

Triazenes have been prepared by the treatment of resin-bound aromatic diazonium salts with secondary amines (Figure 3.27). Regeneration of the amine can be effected by mild acidolysis (Entry 1, Table 3.23). Triazenes have been shown to be stable towards bases such as TBAF, potassium hydroxide, or potassium tert-butoxide [454], and under the conditions of the Heck reaction [455]. Primary amines cannot be linked to supports as triazenes because treatment of triazenes such as R-HN-N=N-Ar-Pol with acid leads to the release of aliphatic diazonium salts into solution [373]. Triazenes derived from primary amines can, however, be used for the preparation of amides and ureas (see Section 3.3.4),... 

Support-bound triazenes, which can be prepared from resin-bound secondary aliphatic amines and aromatic diazonium salts [455], undergo cleavage upon treatment with acids, leading to regeneration of the aromatic diazonium salts. In cross-linked polystyrene, these decompose to yield nitrogen and, preferentially, radical-derived products. If the acidolysis of polystyrene-bound triazenes is conducted in the presence of hydrogen-atom donors (e.g. THF), unsubstituted arenes can be obtained (Entries 8 and 9, Table 3.47). In the presence of alkenes or alkynes and Pd(OAc)2, the initially formed diazonium salts undergo Heck reaction to yield vinylated or alkynylated arenes (Entry 10, Table 3.47). Similarly, unsubstituted arenes can be obtained by oxida-... 

The triazene linker can be used for the immobilization of aromatic diazonium salts, and therefore for aromatic amines, but not for aliphatic amines due to the instability of their diazonium salts. Cleavage of the linker can be achieved under mild acidic conditions to yield the benzylamine resin and the corresponding diazonium salt [136,145,146]. The main difference between the preparation of triazenes in solution and triazenes on solid support is the respective amine, namely bisben-zylamine and polymer-supported benzylamine 114. In solution, it was used in excess to quench unstable diazonium salts and force the reaction to completion. In the solid-phase approach it was immobilized and cannot be used in excess with respect to low loadings. A simple three-step procedure (Scheme 36) starting from benzylamine resin 114 via carboxylate 115 led to the successful preparation of ester resins 116 in essentially higher loadings. Treatment of resin 114 with 4-carboxy-benzene diazonium tetrafluoroborate yielded benzoic acid resin 115. 

Fig. 7. Triazenes as versatile polymer-supported diazoalkane analogues (resins 10) were obtained from polymeric diazonium salts (resins 9) and releasing carbenium ions upon acidic activation. The reaction can be employed for the alkylation of carboxylic acids with a reaction half life of ca. 5 min.

Two kinds of in situ-prepared diazonium salts from amino-esters (203, 206) have been immobilized on polymer-supported benzylamine (202), affording resins (204) and (207). liHMDS-mediated formation of the corresponding enolates and subsequent reactions with a variety of imines afforded the desired resin-bound p-lactams (205, 208). Use of a CH2CI2 solution of TEA allowed detachment of the diazonium salt from the resin, while the removal of the diazo group has been accomplished by means of a mixture of THE and DMF or THF and acetonitrile, both at r. t. for 12 h (Scheme 45). 

Brase and coworkers were the first to introduce triazene linkers for use in SPOC in a seminal report in 2000 [18]. They found immobilized diazonium ions have high stability, which enabled their application as linkers and scavengers. Their synthesis involves the reduction of 3-amino-6-chlorobenzoic acid, which was subsequently coupled onto a Merrifield resin via standard etherification. Subsequent conversion of the amino group into a diazonium salt generated the supported diazonium tet-rafluoroborate, which was found to sequester amines (Scheme 8.12). 

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