Water → (R)-3-(4-Bromophenyl)cyclopentan-1-one

HRID 516933Notes

Reaction equation

HRID 516933 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.O.[C:12]1(=[O:17])[CH2:16][CH2:15][CH:14]=[CH:13]1>O1CCOCC1.[B-](F)(F)(F)F.C1C2C=CC1C=C2.C1C2C=CC1C=C2.[Rh].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:14]2[CH2:15][CH2:16][C:12](=[O:17])[CH2:13]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 962WaterHCID 135882-Cyclopenten-1-oneHCID 79599(4-Bromophenyl)boronic acid

Product 1

HCID 49833221(R)-3-(4-Bromophenyl)cyclopentan-1-oneYield 25.5%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 10915722Bis(norbornadiene)rhodium(I) tetrafluoroborateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-bromophenylboronic acid (20 g, 100 mmol) in 1,4-dioxane (120 mL) was purged with nitrogen for 10 min. (R)-BINAP (0.992 g, 1.593 mmol) and bis(norbornadiene)rhodium (I) tetrafluoroborate (0.559 g, 1.494 mmol) were added sequentially, and the suspension was sonicated for 5 min. The mixture was stirred for 20 min. Water (20 mL) was added, and the reaction mixture became homogeneous. After 10 minutes, cyclopent-2-enone (8.06 mL, 100 mmol) was added, and the reaction mixture was stirred at room temperature overnight. HPLC and LCMS analysis indicated that the reaction had proceeded, but there was more starting material than product. The reaction mixture was filtered through a pad of CELITE®, and the CELITE® was washed with ethyl acetate (100 mL). The filtrate was diluted with an additional ethyl acetate (150 mL), washed with water (2×), washed with brine, and dried over anhydrous sodium sulfate. The product mixture was purified by flash silica gel chromatography using a mixture of ethyl acetate and hexane to give (R)-3-(4-bromophenyl)cyclopentanone (6.09 g, 25.5 mmol) as a white solid. The product was 98% pure by HPLC with a retention time=2.11 min.—(Condition J). LC/MS M+1=241 1H NMR (400 MHz, chloroform-d) δ 7.57-7.39 (m, 2H), 7.22-7.06 (m, 2H), 3.39 (ddd, J=10.9, 6.8, 4.1 Hz, 1H), 2.67 (dd, J=18.2, 7.4 Hz, 1H), 2.57-2.38 (m, 2H), 2.38-2.21 (m, 2H), 1.99-1.85 (m, 1H).

Workup

  1. additionwere added sequentially
  2. customthe suspension was sonicated for 5 min
  3. waitAfter 10 minutes
  4. stirringthe reaction mixture was stirred at room temperature overnight
  5. filtrationThe reaction mixture was filtered through a pad of CELITE®
  6. washthe CELITE® was washed with ethyl acetate (100 mL)
  7. additionThe filtrate was diluted with an additional ethyl acetate (150 mL)
  8. washwashed with water (2×)
  9. washwashed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe product mixture was purified by flash silica gel chromatography
  12. additiona mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-ce2c0e3a653f4227b0d77cf9457adbce
Source dataset
uspto-grants-2015_08
Patent number
US09115054B2

Reaction notes

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