Sulfonyloxy linkers

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. 

The cleavage from arylsulfonate ester linkers on sohd phase goes back to the investigations of Wustrow et al. in which the palladium-catalyzed reductive cleavage of arylsulfonate esters to their hydrogenated equivalents via aryl - 0 bond break is examined [302]. 

It has been shown recently by Park et aL that also Grignard reagents can be used to cleave sulfonate esters [304]. For this traceless biphenyl-forming reaction Ni(0)-catalysts (NiCl2dppe) have to be added to permit ipso nucleophilic aromatic substitution of the alkyloxysulfonyl groups. 

All cross-coupHng approaches on the sulfonate ester Hnker have been tested for various substrates boimd to the polymer, proving that the methodology is compatible with several aromatic systems containing ketones, pyridines, lactones, aldehydes and fluoro-substituents. 

A simple route to sulfonate esters has been presented by Reitz et al. [310, 311] who converted Merrifield resin withp-hydroxy arenesulfonylchlorides to give the corresponding sulfonylchloride resin to which alkylhydroxides can be easily attached in the form of their sulfonate esters 517. 

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Similar concepts describing the formation of novel C-C bonds in the cleavage step were introduced by Holmes et al. [96] and Park et al. [97] Both groups utilized aryl sulfonyloxy linkers that were cleaved by reaction with boronic acids or Grignard reagents to give biphenyl derivatives. Wustrow et al. introduced a... 

Scheme 16.24 Cleavage-hydrogenation reaction with a sulfonyloxy linker according to Wustrow et al.

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