Microwave-Enhanced High-Speed Fluorous Synthesis

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 Pdcatalyzed cross-coupling reactions, free-radical reactions, multicomponent reactions, and compound library synthesis.

Microwave-Assisted Synthesis in Water as Solvent

“…Therefore, safety problems arising from overpressurization of heated sealed reaction vessels can be minimized. Similarly, microwave chemistry has been conducted in conjunction with the use of fluorous solvents or fluorous reagents/catalysts . The advantage of microwave heating lies in the rapid coalescence of the organic and fluorous phase to form a homogeneous solution.…”

Microwave-Assisted Fluorous Synthesis of a 1,4-Benzodiazepine-2,5-dione Library

“…Conducting post condensation reactions can lead to the generation of more complicated molecules. The advantage of using MCRs for construction of structurally diversified molecules can be enhanced through the incorporation of microwave and fluorous technologies 29–31. Combinatorial techniques involving MCR, fluorous linker, and microwave heating have been applied for the synthesis of BDZ libraries.…”

“…Conducting post condensation reactions can lead to the generation of more complicated molecules. The advantage of using MCRs for construction of structurally diversified molecules can be enhanced through the incorporation of microwave and fluorous technologies. − Combinatorial techniques involving MCR, fluorous linker, and microwave heating have been applied for the synthesis of BDZ libraries. It was designed based on following three major transformations: (1) Ugi MCRs invloving benzaldehyde 2 as a fluorous component to form 5 , (2) cyclization of the Ugi products to form BDZs 6 , and (3) formation of 7 by microwave-assisted Suzuki reactions to cleave the F-linker and introduce the biaryl functionality to BDZs.…”

The use of microwave irradiation in the fluorous synthesis

“…A sílica fluorada evita a utilização de solvente fluorado (muitas vezes de custo elevado), é estável e pode ser reutilizada. 11 Além disso, a possibilidade de separar por cromatografia líquida de alta eficiência (CLAE) uma mistura de compostos fracamente fluorados, contendo cadeias perfluoroalquilas de diferentes tamanhos, levou ao desenvolvimento da síntese fluorosa em mistura (Fluorous Mixture Synthesis). 12 4.…”

“…Progressos vêm sendo feitos nesta área, inclusive sua extensão à síntese em fase sólida e à síntese fluorosa. 11 A seguir, exemplifica-se o uso e a grande aplicação destes dois métodos com algumas publicações recentes descritas na literatura para a síntese de compostos de estruturas variadas.…”