Fluorous tagging strategy

The described fluorous-tag strategy has also been applied to the synthesis of biaryl-substituted hydantoins (Scheme 7.81) [94]. 4-Hydroxybenzaldehyde was converted into the corresponding perfluorinated species, which was then subjected to a reductive amination. The resulting amine was treated with an isocyanate to produce the fluorous-tagged urea, which spontaneously cyclized to form the corresponding hydantoin. Finally, the fluorous tag was detached by a Suzuki-type carbon-carbon bond formation to furnish the desired target structure in good yield. 

Z. Luo, Q. Zhang, Y. Oderaotoshi, and D. P. Curran, Fluorous mixture synthesis A fluorous-tagging strategy for the synthesis and separation of mixtures of organic compounds, Science, 291 (2001), 1766-1769. 

Zhang, W. (2004) Fluorous tagging strategy for solution-phase synthesis of small molecules, peptides and oligosaccharides. Curr. Opin. Drug Discov. Develop., 7, 784—797. 

Zhang, Q. S., Rivkin, A. and Curran, D. P. (2002) Quasiracemic synthesis concepts and implementation with a fluorous tagging strategy to make both enantiomers of pyridovericin and mappicine. J. Am. Chem. Soc., 124, 5774—5781. 

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. 

Fluorous chemistry integrates the characteristics of solution-phase reactions and the phase tag strategy developed for solid-phase chemistry [7-15], Perfluoroalkyl chains instead of polymer beads are used as the phase tags to facilitate the separation process. In 2001 the Curran group first reported the concept of fluorous mixture synthesis (FMS) for solution-phase library synthesis [16], FMS is able to produce individual pure compounds without the effort of deconvolution. It adapts literature procedures to synthesize complex natural products, their enantiomers and diastereomers. FMS can also be used for the development of new synthetic protocols and to make novel drug-like molecules [17, 18],... 

The synthetic scope for making murisolin stereoisomers has been extended through the development of the first double tagging strategy [34, 35] A mixture of four stereoisomers of dihydroxytetrahydofuran encoded with four fluorous tags at C-19 and C-20 was... 

Manku, S. and Curran, D. P. (2005) Fluorous mixture synthesis of fused-tricyclic hydantoins. Use of a redundant tagging strategy on fluorinated substrates../. Org. Chem., 70, 4470-4473. 

Figure 5. A strategy for use of a single fluorous tag to allow direct formation of microarrays for biological screening.

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