Sulfonate ester linker

Fig. 15 Polymer-bound sulfonate ester linkers (substrates immobilized)...

The importance of sulfonyloxy—or sulfonate ester—linkers results from their stability under several conditions including compatibihty with Grignard additions, Wittig reactions, NaBH4-reduction, reductive aminations, acylations, Suzuki couplings and treatment with various other electrophiles. Some linkers of the sulfonate ester type are shown in Fig. 15. 

Scheme 79 Cleavage opportunities for aryl components attached on sulfonate ester linker...

The developed sulfonated ester linker 517 has been employed for the synthesis of various amines 549, 551, 553 and thioethers 555 (Scheme 83). The nucleophilic cleavage of the alkyl-0 bond is facihtated because of the transformation of hydroxy functionaUties into good leaving groups. 

Other nucleophiles can be chosen to perform substitutions on sulfonate ester linkers. Roush et al. synthesized alkyliodides 542 via cleavage of oligosaccharides from Merrifield-type resins 541 by addition of Nal to the resin-bound substrates [314]. 

Polystyrene-bound aliphatic sulfonic esters and O-aryl sulfamates can be cleaved by treatment with potassium carbonate or other nucleophiles, whereby the corresponding alcohols are released into solution (Entries 11 and 12, Table 3.34). O-Alkyl sulfamates, on the other hand, do not react with nucleophiles and cannot be used as linkers for alcohols [245],... 

Figure 22 Undirected ABPP probes exploiting sulfonate esters and a-chloracetamide as reactive groups, (a) A probe library with diverse sulfonate esters appended via a linker either to rhodamine or biotin, (b) a-Cloracetamide probes with a variable peptide backbone linked to a rhodamine tag.

This linker allows for the straightforward attachment of phenols as sulfonate esters and also for their use in reductive traceless cleavage and for C-C bond formations during the release from the support. Its efficiency was demonstrated in the synthesis of valsartan methyl ester by a multi-step solid-phase strategy [111]. 

Only a few examples of solid-phase syntheses of phosphonic, phosphoric, and sulfonic acids have been reported (Figure 3.16). Benzyl esters of these strong acids can act as alkylating agents, and may therefore be too labile to serve as linkers for long synthetic sequences on solid phase. However, if cross-linked polystyrene is used as the support, the reactivity of, for example, benzyl sulfonates is strongly reduced, and even... 

The 4-hydroxythiophenol solid support or phenol-sulfide linker 5u [238] can be used for anchoring carboxylic acids in the presence of carbo-diimides to give an acid-stable ester linkage that can be activated toward nucleophilic attack by amines by oxidation to the sulfone. However, although the acid stability has been confirmed, it has been reported that prior oxidation of the anchor is unnecessary for release of amides by reaction with amines by either an intermolecular [239] or intramolecular pathway [240]. 

Using Resin-Bound Vinyl Sulfone. Resin-bound vinyl sulfones have also been used as an alternative sulfone linker unit since they have been shown to be stable to a wider range of conditions compared to the REM benzyl ester system. The vinyl sulfone group reacts efficiently with nucleophilic substrates, such as secondary amines, via conjugate addition. Quaternization of the resin-bound tertiary amine followed by subsequent deamination provided the respective tertiary amine and the regenerated resin-bound vinyl sulfone (Scheme 12.4). 

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