Oxygen → (3S,3aS,7R,7aS)-6,7a-Dimethoxy-3-(4-methoxy-4-methylpentyl)-3-methyl-7-(3-methylbut-2-en-1-yl)-3,3a,7,7a-tetrahydro-2,7-methanobenzofuran-4(2H)-one

Temperature

-78 °C

An EtOAc (30 mL, sparged for 30 min with O2 directly prior to the reaction) slurry of cesium carbonate (12.76 g, 36.2 mmol, 4 equiv.), 31 (3.55 g, 9.04 mmol, 1 equiv.), and a nonane solution of tert-butyl hydroperoxide (5.5 M, 6.6 mL, 36 mmol, 4 equiv.) was cooled to −78° C. in a 3-neck 300-mL round-bottom flask with O2 bubbling through the slurry via glass pipette. An EtOAc (25 mL) solution of bis(trifluoroacetoxy)iodobenzene (11.67 g, 27.1 mmol, 3 equiv.) was added dropwise over 30 min, following by an EtOAc (5 mL) rinse of the flask that contained the bis(trifluoroacetoxy)iodobenzene. The slurry was stirred at −78° C. for 2 h and subsequently slowly warmed to 0° C. over 2.25 h. The resulting pink slurry was subsequently quenched at 0° C. with saturated aqueous Na2S2O3, O2 bubbling was suspended, and the resulting yellow mixture was stirred vigorously at room temperature for 45 min. The mixture was then extracted thrice with EtOAc. The organic extracts were combined, washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a yellow oil. Flash column chromatography (300 mL SiO2, 7:3 hexane:EtOAc) afforded 1.07 g (2.63 mmol, 29% yield) of 32 as a viscous yellow syrup. TLC Rf 0.18 (1:1 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 5.33 (s, 1H), 5.29 (t, J=7.2 Hz, 1H), 3.90 (d, J=5.7 Hz, 1H), 3.70 (s, 3H), 3.46 (s, 3H), 3.12 (s, 3H), 2.67 (s, 1H), 2.41 (dd, J=15.0, 6.1 Hz, 1H), 2.34 (dd, J=14.9, 8.0 Hz, 1H), 2.00 (d, J=13.0 Hz, 1H), 1.93 (dd, J=13.1, 5.7 Hz, 1H), 1.69 (s, 3H), 1.62 (s, 3H), 1.39-1.29 (m, 4H), 1.26 (s, 3H), 1.23-1.11 (m, 2H), 1.09 (s, 6H). 13C NMR (126 MHz; CDCl3): δ 198.0, 181.3, 133.0, 122.1, 115.4, 100.8, 80.7, 74.5, 56.7, 56.4, 52.2, 49.3, 48.6, 48.1, 40.9, 38.8, 34.6, 32.1, 28.0, 26.3, 25.3, 25.0, 18.2, 17.9.

1. customAn EtOAc (30 mL, sparged for 30 min with O2 directly
2. washrinse of the flask that
3. temperaturesubsequently slowly warmed to 0° C. over 2.25 h
4. customThe resulting pink slurry was subsequently quenched at 0° C. with saturated aqueous Na2S2O3, O2 bubbling
5. stirringthe resulting yellow mixture was stirred vigorously at room temperature for 45 min
6. extractionThe mixture was then extracted thrice with EtOAc
7. washwashed with H2O and brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo to a yellow oil

ORD record

ord-9c4125b528d44289a8c619aef0d1162a

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321713B2