Other fluorous reagents

Fluorous DEAD was prepared and used in a Mitsunobu reaction.Fluorous triaryl phosphine was used for a Wittig reaction.Fluorous boronates were prepared and used in functional transformations and a Suzuki-Miyaura coupling reaction. 

Fluorous carbodiimide was used for dipeptide and ester synthesis. The reaction was carried out in CH2CI2 and FC-72, and the fluorous urea byproduct was extracted in the FC-72 using perfluoroheptanoic acid. The acid formed a stable complex with the fluorous urea and the solubility of the complex in FC-72 was dramatically increased compared with the fluorous urea. 

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An important reagent in fluorous chemistry is the fluorous version of the Marshall resin, dubbed FluoMar (4). This separation tag is reported to dissolve readily in dichloromethane, tetrahydrofuran, and ethyl acetate and can, as many other fluorous reagents, be monitored by traditional chromatographic and spectroscopic methods. The usefulness of (4) was demonstrated in a multistep parallel synthesis of a 3 X 3 array of diamides, where the final products were efficiently purified by F-SPE and cleaved from the FluoMar tag. Tentative results indicated that the homogeneous kinetics of the soluble (4) resulted in reactions that proceeded approximately three times faster than polymer-support bound reactions using standard Marshall resin. 

In the last few years fluorous combinatorial chemistry has been extended and augmented by other fluorous techniques developed by analogy with established methods in solid-phase-supported synthesis. Use of fluorous condensation reagents for the Mitsunobu reaction [23] enables easy removal of all condensation reagents except the coupled starting materials after the reaction [24] (Scheme 3.23). A fluorous variant of the Swern [25] and Corey-Kim oxidations [26] enables handling of stoichiometric quantities of malodorous dimethyl sulfide to be avoided [27] (Scheme 3.24). 

One of the first applications of fluorous synthesis was the use of a fluorous tin hydride 1 (Scheme 13) in radical reactions. The fluorous chains on the tin enable removal by fluorous-organic extraction, but at the same time, the solubility of 1 in benzene and other organic solvents is dramatically decreased. Consequently, reduction of 2 using 1 in benzene gave only low yields of reduced product. However, BTF is able to solubilize both the organic substrate and the fluorous reagent 1, and reduction of adamantyl bromide in BTF gave adamantane 3 in 90% yield (Scheme 13). 

The distribution of solutes between the two phases can be estimated by measurement of the relative solubility of the reagent in each phase of the system under given physical conditions. Water and 1-octanol have become a standard solvent mixture for this [21], although other pairs of solvents may be used to produce, for example, a scale of preference for fluorous versus organic solvents, as described below. The quantity P, known as the partition coefficient, is defined as... 

Other means for generation and annulation of aryl radicals involve treatment of A -(t>-bromophenyl)propylamides with BusSnH/AIBN, which gives 3-alkylideneoxindoles <2(X)0J(P1)763>, or exposure of A -allyl(t>-iodoanilines) to fluorous tin hydride reagents, affording indolines <1999JA6607>. A set of indolines, for instance 239, have been obtained by radical cyclization of precursors such as 240, which were derived from A -allylanilines (Equation 76) <1999TL2533>. 

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