Phase-Vanishing Methods Based on Fluorous Phase Screen: A Simple Way for Efficient Execution of Organic Synthesis

The phase-vanishing (PV) method is based on spontaneous reaction controlled by diffusion of reagents into fluorous media, such as perfluorohexanes (FC-72) and polyperfluoroethers. Thus, the original PV reaction utilizes a triphasic test tube method composed of a bottom reagent phase, a middle fluorous phase, and a top substrate phase. In such a triphasic system, the fluorous phase acts as a liquid membrane to transport the bottom reagents to the top organic phase containing substrates. In the end, the bottom layer disappears and two phases remain. Since the first demonstration of the PV method by bromination of alkenes with molecular bromine, a number of applications have been developed thus far. These include halogenation of alcohols with SOBr2 and PBr3, demethylation of methoxyarenes with BBr3, cyclopropanation of alkenes by CH2I2-AlEt3, and Friedel-Crafts acylation of aromatic compounds with SnCl4. A fluorous triphasic U-tube method is effective for chlorination of alcohols based on lighter (less dense) reagents such as SOCl2, and PCl3. A system using a solution containing reagents as a bottom phase is useful for oxidation with m-CPBA, which may be defined as a new category for the extractive PW method. Recent advances include a quadraphasic PV method, in which an aqueous 11 scavenger 11 phase is added to the original triphasic PV method to remove acidic by-products. (c) 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 351-363; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20161