Sulfone Linker Units

The linker is a vital component in solid-phase synthesis. It should be stable enough to tolerate aU the reaction conditions and, on the other hand, be sensitive enough to be cleaved after the reaction is completed. Hence, to accommodate the increasing number of reaction conditions that are being adapted for solid-phase synthesis, a large number of sophisticated linker units have been developed and employed in solid-phase synthesis. In this chapter, we will focus exclusively on the sulfone linker unit and its applications in the synthesis of heterocycles. 

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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). 

Besides heterocyclic synthesis, the sulfone linker unit has also been applied to the preparation of a variety of other substrates. " " " " The diverse cleavage strategies that can be applied to cleave substrates from sulfone linkers make them a versatile multifunctional linker. This together with the simple purification process, compared to solution-phase synthesis, adds to the potential of sulfone chemistry being applied to solid-phase synthesis. 

Oxidation to the sulfoxide or sulfone can also be used as a method to activate sulfur linker units. Typically, it is easier to oxidize aU the way to the sulfone, but specialized strategies have been developed that allow intermediate oxidation to the sulfoxide. Moreover, sulfoxides can be loaded onto resins directly ", but it is far more common to... 

Certain linker units lend themselves to the solid-phase synthesis of oligosaccharides. Roush and Hunt cleaved trisaccharides 121 from a sulfone-based linker unit using a nucleophile (Nu = iodide, sodium acetate, or sodium azide) to provide sugars ready for additional substitution, if required (Scheme 3.24). ... 

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