An Alkene-Forming Cascade Reaction En Route to 2,2'-Bi(glycerol)

Abstract

Synthesis of 2,3-bis(hydroxymethyl)butane-1,2,3,4-tetraol is of great interest because of its utility as a potential precursor to new dendrimers, in the preparation of unnatural lipids, and in the synthesis of open-framework coordination polymers. Synthesis of this new six-­hydroxyl compound is achieved in four steps from commercially available starting materials. In this process, a new olefin-forming cascade ­reaction was discovered.

Key words

cascade reaction - alkenes - olefins - 2,2'-bi(glycerol) - hexa­alcohol

• References and Notes

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• 14 2,2,2',2'-Tetramethyl[5,5']bi[1,3]dioxanylidene (7) At r.t., under a N₂ atmosphere, NaH (60% dispersion in mineral oil, 1.05 g, 26 mmol) was added slowly to N,N-dimethylacetamide (DMA, 5 mL). A solution of 12 (1.22 g, 5.08 mmol) in DMA (5 mL) was added dropwise to the stirred NaH suspension at r.t. The temperature of the mixture was raised quickly to 80–90 °C by placing it in a preheated oil bath. After 4 h, the reaction mixture was allowed to cool to r.t., quenched in ice-cold water (10 mL), and extracted with anhydrous diethyl ether (3 x 15 mL). The combined organic extracts were washed with cold water (20 mL), dried with anhydrous Na₂SO₄, filtered, and the solvent evaporated under reduced pressure. The residue was purified by silica gel flash chromatography (hexanes/EtOAc 4:1) to yield a white solid (306 mg, 52.8%), mp 133.5–135 °C. ¹H NMR (400 MHz, CD₃COCD₃): δ = 4.22 (s, 4 H) 1.31 (s, 6 H) ppm. ¹³C NMR (100 MHz, CD₃COCD₃): δ = 125.7, 99.0, 58.2, 22.3 ppm.
• 15 2,2,2',2'-Tetramethyl-[5,5']bi[[1,3]dioxanyl]-5,5'-diol (8) In a 50 mL round-bottomed flask equipped with magnetic stirring bar were stirred NaIO₄ (160 mg, 0.75 mmol) and CeCl₃·7H₂O (19 mg, 0.051 mmol) in water (0.25 mL) and gently heated until a bright yellow suspension was formed. After cooling to 0 °C, ethyl acetate (0.63 mL) and acetonitrile (0.75 mL) were added, and the suspension was stirred for 2 min. RuCl₃ (2.1 mg, 0.010 mmol) was added and the mixture was stirred for 2 min. A solution of olefin 7 (114 mg, 0.499 mmol) in ethyl acetate (0.25 mL) was added in one portion. The mixture was stirred until the starting material disappeared, monitored by TLC (hexanes/EtOAc 4:1) every half hour. Na₂SO₄ (250 mg) was added followed by EtOAc (3 mL). The solid was filtered off. The filtrate was washed with saturated Na₂SO₃ (1.2 mL) solution. The organic layer was dried with Na₂SO₄ and concentrated with a rotary evaporator. The crude product was purified by chromatography on silica gel (hexanes/EtOAc 2:1) to give a white solid, (83 mg, 63% yield), mp 187–190 °C. ¹H NMR (400 MHz, CDCl₃): δ = 4.23 (d, 4 H, J = 12.0 Hz), 3.57 (d, 4 H, J = 12.0 Hz), 3.31 (s, 2 H), 1.46 (s, 6 H), 1.43 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 98.7, 69.3, 64.5, 27.3, 20.0 ppm.
• 16 2,3-Bis(hydroxymethyl)butane-1,2,3,4-tetraol (1) At 0 °C, trifluoroacetic acid (0.10 mL, 1 mmol) was added to a solution of 8 (71 mg, 0.27 mmol) in aqueous THF (2.5 mL, THF/H₂O 4:1). The mixture was stirred at r.t. for 3 h. The solution was evaporated with a rotary evaporator affording a colorless oil. After standing for several days, the colorless oil solidified, giving 1 (39 mg, 79% yield). ¹H NMR (400 MHz, D₂Ο): δ = 3.69 (s) ppm. ¹³C NMR (100 MHz, D₂O): δ = 76.9, 61.8 ppm.