Hydantoins, solid-phase approach

For this solid-phase approach, conventional iPrOCH2-functionalized polystyrene resin (Merrifield linker) was employed. After attachment of the requisite substrate, the resin was pre-swollen in a solution of barium(II) hydroxide in N,N-dimethyl-formamide within an appropriate sealed microwave vial. The vial was heated in the microwave cavity for 5 x 2 min cycles (overall 10 min) with the reaction mixture being allowed to cool to room temperature in between irradiation cycles (Scheme 7.50), leading to comparatively modest isolated yields of hydantoins. 

Figure 15.4 Solid-phase approach to tetrahydro-pi-carboline hydantoins.

In a related approach from the same laboratory, the perfluorooctylsulfonyl tag was employed in a traceless strategy for the deoxygenation of phenols (Scheme 7.82) [94], These reactions were carried out in a toluene/acetone/water (4 4 1) solvent mixture, utilizing 5 equivalents of formic acid and potassium carbonate/[l,T-bis(diphe-nylphosphino)ferrocene]dichloropalladium(II) [Pd(dppf)Cl2] as the catalytic system. After 20 min of irradiation, the reaction mixture was subjected to fluorous solid-phase extraction (F-S PE) to afford the desired products in high yields. This new traceless fluorous tag has also been employed in the synthesis of pyrimidines and hydantoins. 

In an earlier report, the microwave-mediated intramolecular carbanilide cyclisation to hydantoins was described44. Since the hydantoin moiety imparts a broad range of biological activities, several protocols involving both reactions in solution and on solid-phase have been investigated. Within this report, the first microwave-assisted synthetic approach to hydantoins is described (Scheme 7.36). 

The hydantoin scaffold is among the earliest described diversity-generating systems in combinatorial chemistry [12]. The first procedures were appropriate for syntheses of small arrays, but not suitable for large libraries. Practical limitations such as the small range of suitable building blocks available from commercial vendors, as well as conceptual limitations in the number of diversity sites modifiable directly on the solid phase, made it necessary to design improved approaches for a more extensive exploitation of this template s diversity potential. 

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