Fluorous chemistry

A SAMPLE OF REVIEWS ON SOLID PHASE SYNTHESIS General 

Blackburn, Polymer supports for solid-phase organic synthesis, Biopolymers XI 311-351 1998. 

Booth and J.C. Hodges, Solid-supported reagent strategies for rapid purification of combinatorial synthesis products, Acc Chem Res 32 18-26 1999. 

Ellman, Design, Synthesis, and Evaluation of Small-Molecule Libraries, Acc Chem. Res 29 132-143 1996. 

Fruchtel and G. Jung, Organic Chemistry On Solid Supports, Angew Chem, Int Ed Engl 35 17-42 1996. 

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The book also outlines recent developments in synthe (e.g., combinatorial chemishy, solid support chemistry, fluorous chemistry) and the corresponding purification procedures that will provide maiiy of the commercially supplied chrnnical substances in years to come. Additionally, interesting perspective out the future of purification Is jHovided by the autiuxrs, based on their years of experience. 

Gladysz JA, Curran DP, Horvath IT (eds) (2004) Handbook of Fluorous Chemistry. WUey, Weinheim... 

Metrangolo P, Pilati T, Resnati G (2004) Self-assembly of hybrid fluorous materials. In Gladysz JA, Curran DP, Horwath IT (eds) Handbook of fluorous chemistry. Wiley, Weinheim, p 507... 

Some of the disadvantages of the Stille reaction, e. g. the low reactivity of some substrates, separation difficulties in chromatography, and the toxicity of tin compounds, have been ameliorated by recent efforts to improve the procedure. Curran has, in a series of papers, reported the development of the concept of fluorous chemistry, in which the special solubility properties of perfluorinated or partly fluorinated reagents and solvents are put to good use [45]. In short, fluorinated solvents are well known for their insolubility in standard organic solvents or water. If a compound contains a sufficient number of fluorine atoms it will partition to the fluorous phase, if such a phase is present. An extraction procedure would thus give rise to a three-phase solution enabling ready separation of fluorinated from nonfluorinated compounds. 

Among the many applications of fluorous chemistry is the Stille coupling of tin reagents with fluorinated tags in which the products and excess of the tin-containing reagents can be conveniently removed from the reaction mixture, and recycled. Un-... 

In an additional application of fluorous chemistry, radical-mediated cyclizations were performed in benzotrifluoride using microwave irradiation [70]. In the pre-... 

Many of these new techniques are especially suited to the preparation of combinatorial libraries by solution phase parallel synthesis. This chapter provides a brief introduction to the concepts of strategy level purification, and then introduces fluorous chemistry with representative examples of reactions, reagents and techniques. 

J.A. Gladysz, D.P. Curran, I. Horvath, Handbook of Fluorous Chemistry, Wiley-VCH, Weinheim, 2004. 

Tin hydrides bearing highly fluorinated substituents (fluorous chemistry) were used in the radical-mediated reduction of 1-bromoadamantane. The reaction was complete within 3 min under 35 W microwave irradiation (Scheme 4.42)68. 

The time consuming chromatographical purification of heterocycles 28 and 29 slowed down the rate of library production. A phase separation using fluorous chemistry was employed by Zhang and Lu to address the workup and purification of fused 3-aminoimidazo[ l,2-a]pyridines (such as 30) [54]. Thus, attachment of a perfluorooctanesulfonyl tag to aldehydes and subsequent Ugi three-component microwave-assisted condensations with 2-aminopyridines and isocyanides furnished the desired heterocycles 30, which were conveniently isolated by fluorous solid-phase extraction. The fluorous tag could be subsequently used as an activating group in the post-condensation modifications, such as Suzuki-Miyaura cross-coupling reactions. 

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