SULFONES IN SOLID-PHASE HETEROCYCLE SYNTHESIS

Solid-Phase Organic Synthesis Concepts, Strategies, and Applications, First Edition. Edited by Patrick H. Toy and Yulin Lam. 

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. 

---

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

This traceless linker allows fhe synthesis of a number of different heterocycles starting from fhe solid-phase-bound sulfone intermediate 139, which can be built up in a few steps from fhe sulfinate 138. The potential of fhis traceless linker is outlined in Scheme 66 [161, 162]. 

---