Aryl fluorous-phase synthesis

Scheme 7.78 Fluorous-phase palladium-catalyzed synthesis of aryl sulfides.

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. 

Fluorous ligands introduce an ease of purification in that the tagged phosphine ligand, the palladium catalyst complexed ligand, and the oxidized ligand can be completely removed by direct fluorous solid-phase separation (F-SPE) prior to product isolation. Similarly, an example of a fluorous palladium-catalyzed microwave-induced synthesis of aryl sulfides has been reported, whereby the product purification was aided by fluorous solid-phase extraction [91]. 

One early example of microwave-assisted fluorous synthesis involved palladium-catalyzed Stifle couplings of fluorous tin reagents with aryl halides or triflates (Scheme 16.59) [90]. The desired biaryl products were isolated in good yields and purity after a three-phase extraction. Similar results were also achieved by use of so-called F-21 fluorous tags (CFl2CFl2CioF2i) on the tin reagent [91]. 

---