Dichloromethane → (1S,5R,7S,8S,9S)-7,9-Dihydroxy-4,9-dimethoxy-8-methyl-3,5-bis(3-methylbut-2-en-1-yl)-8-(4-methylpent-3-en-1-yl)bicyclo[3.3.1]non-3-en-2-one

HRID 633651Notes

Reaction equation

HRID 633651 reaction equation
C(Cl)Cl.[CH3:4][O:5][C:6]1[C@@:7]2([CH2:31][CH:32]=[C:33]([CH3:35])[CH3:34])[CH2:13][CH:11]3[O:12][C@@:8]2([O:29][CH3:30])[C@H:9]([C:21](=[O:28])[C:22]=1[CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[C@:10]3([CH3:20])[CH2:14][CH2:15][CH:16]=[C:17]([CH3:19])[CH3:18].BrB(C)C.CCCCCC.CC[O:48]C(C)=O>>[OH:12][C@@H:11]1[C@@:10]([CH3:20])([CH2:14][CH2:15][CH:16]=[C:17]([CH3:18])[CH3:19])[C@@H:9]2[C@:8]([OH:48])([O:29][CH3:30])[C@@:7]([CH2:31][CH:32]=[C:33]([CH3:34])[CH3:35])([C:6]([O:5][CH3:4])=[C:22]([CH2:23][CH:24]=[C:25]([CH3:26])[CH3:27])[C:21]2=[O:28])[CH2:13]1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 8058HexaneHCID 8857Ethyl AcetateHCID 123224DimethylboronbromideHCID 86718443(3S,3aS,7R,7aS)-6,7a-Dimethoxy-3-methyl-5,7-bis(3-methylbut-2-en-1-yl)-3-(4-methylpent-3-en-1-yl)-3,3a,7,7a-tetrahydro-2,7-methanobenzofuran-4(2H)-one

Product 1

HCID 86718442(1S,5R,7S,8S,9S)-7,9-Dihydroxy-4,9-dimethoxy-8-methyl-3,5-bis(3-methylbut-2-en-1-yl)-8-(4-methylpent-3-en-1-yl)bicyclo[3.3.1]non-3-en-2-oneYield 88%

Conditions

Temperature
-78 °C

Procedure

A DCM (2 mL) solution of 15 (29 mg, 6.6 μmol, 1 equiv.) was cooled to −78° C. in a 10-mL teardrop-shaped flask, and a DCM solution of bromodimethylborane (2.65 M, 0.25 mL, 0.66 mmol, 10 equiv.) was added dropwise. After stirring the bright yellow solution at −78° C. for 10 min, it was quenched sequentially at −78° C. with 1.25 mL NEt3 and saturated aqueous NaHCO3. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to yield a yellow residue. Flash column chromatography (30 mL SiO2, 9:1 hexane:EtOAc) afforded 26.7 mg (58 μmol, 88% yield) of 17 as a yellow oil. TLC Rf 0.38 (7:3 hexane:EtOAc). 1H NMR (600 MHz; C6D6): δ 5.55 (dq, J=11.5, 1.3 Hz, 1H), 5.35 (t, J=7.3 Hz, 1H), 5.28 (t, J=6.6 Hz, 1H), 3.71 (s, 1H), 3.67 (dd, J=11.8, 5.3 Hz, 1H), 3.53 (s, 3H), 3.34 (dd, J=15.2, 6.4 Hz, 1H), 3.16 (m, 1H), 3.14 (s, 1H), 3.06 (s, 3H), 2.92 (dd, J=14.1, 11.5 Hz, 1H), 2.86 (tdd, J=12.8, 7.7, 5.0 Hz, 1H), 2.26 (d, J=14.1 Hz, 1H), 2.08 (tt, J=12.5, 6.1 Hz, 1H), 2.00 (dd, J=12.8, 12.0 Hz, 1H), 1.84 (s, 3H), 1.72 (s, 3H), 1.72-1.68 (m, 1H), 1.62 (s, 6H), 1.60-1.58 (m, 1H), 1.56 (s, 3H), 1.42 (s, 3H), 1.27 (td, J=12.7, 4.4 Hz, 1H), 1.12 (s, 3H). 13C NMR (126 MHz; C6D6): δ 197.3, 171.2, 136.5, 131.8, 131.1, 125.8, 124.5, 123.36, 123.23, 100.2, 73.4, 61.8, 57.5, 52.4, 48.2, 40.9, 39.7, 37.5, 30.8, 26.0, 25.76, 25.72, 23.7, 22.2, 18.01, 17.90, 17.7, 17.3. FTIR (thin film) νmax: 3464 (br), 2969, 2928, 2859, 1665, 1615, 1450, 1376, 1329, 1235, 1087, 1040, 986, 928, 907, 858, 737 cm-1. HRMS-ESI (m/z): [M+H]+ calculated for C28H44O5, 461.3262. found, 461.3254.

Workup

  1. customit was quenched sequentially at −78° C. with 1.25 mL NEt3 and saturated aqueous NaHCO3
  2. temperatureThe mixture was warmed to room temperature
  3. extractionextracted thrice with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto yield a yellow residue

Sources & evidence

ORD record
ord-d6e653984ff944bb909408af34876469
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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