Fluorous-phase organic synthesis

Fluorous-phase organic synthesis is a novel separation and purification technique for organic synthesis and process development. This technique involves the use of 

In another application of fluorous chemistry, radical-mediated cyclizations with benzotrifluoride (BTF) as solvent have been investigated under microwave irradiation conditions [90]. In the presence of 2,2 -azobisisobutyronitrile (AIBN) as radical initiator, the aryl iodide used smoothly underwent microwave-mediated cycliza-tion to the corresponding indole derivative in high isolated yield [91]. 

764 I 76 Microwave-asisted Combinatorial and High-throughput Synthesis 

The same group also reported further investigation of fluorous-phase palladium-catalyzed carbon-carbon couplings [94]. Fluorinated aryl octylsulfonates were re- 

Schetne 16.61. Generation of dihydropteridinones by cyclative cleavage from a fluorous tag. 

---

Nishikido, J., Nakajima, H., Saeki, T., Ishii, A., and Mikami, K. 1998. Lanthanide perfluoroalkylsulfonylamide catalysts for fluorous phase organic synthesis. Synlett 1347-1348. 

A. Studer, S. Hadida, R. Ferritto, S.Y. Kim, P. Jeyer, P. Wipf, D.P. Curran, Fluorous synthesis — A fluorous-phase strategy for improving separation efficiency in organic synthesis. Science 275 823-826 1997. 

In comparison with traditional biphasic catalysis using water, fluorous phases, or polar organic solvents, transition metal catalysis in ionic liquids represents a new and advanced way to combine the specific advantages of homogeneous and heterogeneous catalysis. In many applications, the use of a defined transition metal complex immobilized on a ionic liquid support has already shown its unique potential. Many more successful examples - mainly in fine chemical synthesis - can be expected in the future as our loiowledge of ionic liquids and their interactions with transition metal complexes increases. 

D. P. Curran, S. Hadida, Tris(2-(Perfluorohexyl)tin Hybride A New Fluorous Reagent for Use in Traditional Organic Synthesis and Liquid Phase Combinatorial Synthesis , J. Am. Chem. Soc 1996,118,2531. 

B. Linclau, A. K. Singh, D. P. Curran, Organic-Eluorous Phase Switches A Fluorous Amine Scavenger for Purification in Solution Phase Parallal Synthesis , J. Org. Chem 1999, 64, 2835. 

Curran, D. P. Hoshino, M. Stille Couplings with Fluorous Tin Reactants— Attractive Features for Preparative Organic Synthesis and Liquid Phase Combinatorial Synthesis, J. Org. Chem. 1996, 61, 6480-6481. 

Studer, A. Hadida, S. Ferritto, R. Kim, S.-Y. Jeger, P. Wipf, R Curran, D. P. Fluorous Synthesis A Fluorous-Phase Strategy for Improving Separation Efficiency in Organic Synthesis, Science, 1997, 275, 823. 

Abstract Increasing reaction speed and simplifying product purification are two major ways to improve the efficiency of organic synthesis. A new technology for high-speed solution-phase synthesis has been developed by combination of microwave heating and fluorous purification. This review describes different techniques for microwave-enhanced fluorous synthesis and their applications in Pd-catalyzed cross-coupling reactions, free-radical reactions, multicomponent reactions, and compound library synthesis. 

---