Thermal Retro-Aldol Reaction Using Fluorous Ether F-626 as a Reaction Medium

Abstract

A high-boiling, fluorous-organic hybrid ether, F-626, was tested for use in thermal retro-aldol reactions and found to be an excellent reaction medium in view of the ease of separation from the product by fluorous/organic biphasic treatment. The recovered F-626 can be readily reused for subsequent runs.

retro-aldol reaction - fluorous ether - F-626 - biphasic system

References and Notes

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<A NAME="RU04110ST-8">8</A>

General procedure for retro-aldol reactions using F-626: α-Hydroxymethyl ketone 1a (0.5 mmol, 104.7 mg) and F-626 (4 mL, 5.64 g) were placed in a 5 mL two-necked round-bottom flask, and heated at 200 ˚C for 4 h under nitrogen. After cooling to room temperature, the reaction mixture was poured into a separation funnel, and MeCN (4 mL) was added. The MeCN layer was separated, and extracted with FC-72 (6 × 0.33 mL). The combined fluorous layers were evaporated to give F-626 (5.53 g, 98%). The crude reaction mixture obtained from the MeCN layer was purified by silica gel chromatography (hexane-EtOAc, 98:2) to give a mixture of 2a and 3a (87.6 mg; 2a/3a = 95:5)

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<A NAME="RU04110ST-12">12</A>

To a 5 mL two-necked flask, RuHCl(CO)(PPh₃)₃ (0.05 mmol, 48.1 mg), benzene (3 mL) and 2-hexene-1-ol (1 mmol, 101.1 mg) were added, and the resulting mixture was heated at 80 ˚C for 10 h under nitrogen. After cooling to room temperature, the solvent was removed under reduced pressure, F-626 (4 mL) was added and the mixture was heated at 200 ˚C for 4 h. Biphasic workup using MeCN and FC-72, followed by purification using silica gel chroma-­tography (hexane-EtOAc, 98:2) gave a mixture of 2g and 3g (51 mg; 2g/3g = 96:4)