Fluorous solid-phase extraction F-SPE

Furthermore, multicomponent reactions can also be performed under fluorous-phase conditions, as shown for the Ugi four-component reaction [96], To improve the efficiency of a recently reported Ugi/de-Boc/cyclization strategy, Zhang and Tempest introduced a fluorous Boc group for amine protection and carried out the Ugi multicomponent condensation under microwave irradiation (Scheme 7.84). The desired fluorous condensation products were easily separated by fluorous solid-phase extraction (F-SPE) and deprotected by treatment with trifluoroacetic acid/tet-rahydrofuran under microwave irradiation. The resulting quinoxalinones were purified by a second F-SPE to furnish the products in excellent purity. This methodology was also applied in a benzimidazole synthesis, employing benzoic acid as a substrate. 

Zhang, W. and Curran, D.P. 2006. Synthetic applications of fluorous solid-phase extraction (F-SPE). Tetrahedron, 62 11837-65. 

Zhang and co-workers [186] reported a microwave-assisted one-pot, three-component [3-f2] cycloaddition reaction of a fluorous amino ester, an aldehyde and a maleimide to afford bicyclic prolines 135 in yields up to 94%. Fluorous solid phase extraction (F-SPE) has been used effectively to separate the product from the reaction mixture (Scheme 105). 

Another interesting development is the use of fluorous-based scavengers in conjunction with microwave synthesis and fluorous solid-phase extraction (F-SPE) for purification. This was recently illustrated by Werner and Curran [74] in their investigation of the Diels-Alder cycloaddition of maleic anhydride to diphenylbutadiene (Scheme 11.23). After performing microwave-assisted cycloaddition (160 °C, 10 min) with a 50% excess of the diene, the excess diene reagent was scavenged by a structurally related maleimide fluorous dienophile under the same reaction conditions. Elution of the product mixture from an F-SPE column with Me0H-H20 provided the desired cycloadduct 89 in 79% yield and 90% purity. Subsequent elution with diethyl ether furnished the fluorous Diels-Alder cycloadduct. 

In a related approach from the same laboratory the perfluorooctylsulfonyl tag was also used in a traceless strategy for deoxygenation of phenols [95]. After irradiation for 20 min the reaction mixture was subjected to fluorous solid-phase extraction (F-SPE) to afford the desired products in high yields. This new traceless fluorous tag has also been used for synthesis of pyrimidines and hydantoins. 

The final quinoxalinone product 48 was generated by de-Boc cyclization of 48 in TFA-THF (1 1) under the same MW conditions. The product 48 was easily separated from the reaction mixture by fluorous solid-phase extraction (F-SPE) in 51-95% yield. 

Zhang et al. (2006) have reported an advance fluorous synthesis of hydantoin-, piperazinedione-, and benzodiazepinedione-fused tricyclic and tetracyclic ring systems using a sequence of microwave-assisted, fluorous multicomponent reactions (F-MCRs) and fluorous solid-phase extractions (F-SPEs). They used microwave-assisted one pot, three-component [3+2] cycloaddition of azomethine ylides with... 

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