A Grignard-Type Phase-Vanishing Method: Generation of Organomagnesium Reagent and Its Subsequent Addition to Carbonyl Compounds

Abstract

A quadraphasic phase-vanishing system comprised of ether, magnesium, perfluoropolyether, and iodoalkane generated Grignard reagents efficiently, which subsequently added to carbonyl compounds in the ether layer to afford alkylated alcohols in good yields.

Phase-vanishing method with gas evolution and its application to organic synthesis

“…1 Meanwhile, we developed a novel synthetic methodology using fluorous solvents as a phase screen, known as the 'phase-vanishing (PV) method'. [2][3][4][5] The PV method involves a triphasic reaction system, in which fluorous media are used as a liquid membrane to steadily transport reagents from the lower layer to the upper organic layer that includes the substrate. In the PV method, the fluorous phase regulates the transport of reagents by passive diffusion.…”

“…For instance, we demonstrated a Grignard-type reaction using a quadraphasic PV system comprising a 1:1 mixture of Galden HT135 and HT200, 6 iodomethane, magnesium, ether, and carbonyl compounds. 4 In this method, alkyl magnesium iodide reagents were successfully generated in situ and reacted with carbonyl compounds, affording the desired products in good yields.…”

Properties of PTFE tape as a semipermeable membrane in fluorous reactions

“…An important requirement of PV reactions is that, in order to ensure an effective reaction, the rate of passive diffusion of the reagent through the fluorous phase to the substrate layer must be significantly greater than the diffusion of the substrate to the reagent layer [ 9 ]. Ryu and Curran’s work was followed by numerous improved and modified designs including a quadraphasic/tetraphasic PV reaction [ 10 ], a photochemical PV reaction [ 11 – 12 ], a stacked phase-vanishing reaction [ 13 ], a PV reaction on neat substrates [ 11 , 14 – 16 ] and, most recently, a Grignard reaction [ 17 ]. Jana and Verkade reported a variation of the PV method that allows the use of lighter reagents without the need for a U-tube by dissolving one of the reagents in a heavy solvent [ 18 ].…”

An Optimised Procedure for PTFE Phase Vanishing Reactions: An Improved reaction Design and the use of Reagents Adsorbed on Silica

“…It replaces the reaction solvent with an inert perfluoroalkane as a phase screen. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The solvent provides a reaction medium for the reactants and it also helps dissipate the heat of the reaction. The role of the fluorous phase screen is to separate the reagent from the substrate, which provides a way to carry out reactions under ambient conditions on neat reactants.…”

“…4,8,15,16 Bromination was one of the first reactions that was developed as a phase-vanishing fluorous reaction. 1,2 Other groups [3][4][5][6][7][8][9][10][11][12][13][14] and ourselves 15,16 have made improvements to the original PV procedure and applied it to various systems.…”