Second Generation Phase-vanishing Method

Highly fluorinated solvents (fluorous solvents) have unique characteristics: immiscibility with water or organic solvents, and higher density than conventional solvents. These characteristics are cleverly applied in the phase-vanishing (PV) method. Fluorous solvents are used as liquid membranes to regulate reactions by passive diffusion of reagents through the media. Herein, we summarize second generation PV systems, where active species are generated from reagents diffused into the fluorous phase, which subsequently react with substrates to afford the desired products. For example, in photo-irradiative PV reactions, diffused Br-2 was reacted with organic solvents in the fluorous phase to afford HBr by photoirradiation, and subsequently the generated HBr added to alkenes. In Grignard-type PV reactions, diffused alkyl iodide was reacted with magnesium at the border between the fluorous and organic phases to afford alkylmagnesium iodide, which added to carbonyl compounds. In a PV reaction with acetylene evolution, diffused water was reacted with calcium carbide to generate acetylene gas, which underwent several reactions such as Sonogashira coupling. These PV reactions can be called spontaneous molecular level two-step flow-reaction systems. The influence of fluorous phase characteristics such as surface area and viscosity on the bromination of alcohol with Br-2/PPh3, and PV reactions using improved reaction vessels are also described.