Indole → 2-Phenylindole

HRID 590008Notes

Reaction equation

HRID 590008 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:10]1(C)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([Mg]Cl)(C)(C)C.ClC1C=CC=CC=1>CC1(P(C(C)(C)C)C(C)(C)C)C(C2C=CC=CC=2)(C2C=CC=CC=2)C1.O.C1COCC1>[C:10]1([C:2]2[NH:1][C:9]3[C:4]([CH:3]=2)=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 798IndoleHCID 1140TolueneHCID 7964ChlorobenzeneHCID 178418310HCID 178418310, compound

Product 1

HCID 136982-PhenylindoleYield 96%

Reagents, catalysts & solvents 3

HCID 21909131Di-tert-butyl(1-methyl-2,2-diphenylcyclopropyl)phosphaneCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

[PdCl(π-allyl)]2 (15.6 mg, 0.1 mol %) and cBRIDP (60.2 mg, 0.4 mol %) were placed into a 50 mL, two-necked, round bottomed flask equipped a gas inlet, and the flask was evacuated and filled with nitrogen. Subsequently, to the mixture was added dehydrated THF (11 mL) to prepare a catalyst solution. A 200 mL, four-necked, round-bottomed flask equipped with a Teflon® coated magnetic stirring bar, condenser, dropping funnel, thermometer, and a gas inlet was evacuated and filled with nitrogen. Indole (5.0 g, 42.7 mmol, 1.0 equivalent) and dehydrated toluene (55 mL) were charged into the flask, and the mixture was cooled to 5° C. using an ice bath. To the mixture was added a THF solution of tert-butylmagnesium chloride (tBuMgCl) (1.02 mol/L, 46.0 mL, 47.0 mmol, 1.1 equivalents) (containing 42.0 mL of THF) dropwise via the dropping funnel at such a rate that the temperature of the reaction solution was kept at 15° C. or lower. Subsequently, to the solution were added chlorobenzene (4.8 mL, 47.0 mmol, 1.1 equivalents) and the catalyst solution (11 mL) successively, and the solution was stirred for 15 minutes under reflux. After cooling the reaction mixture to room temperature, to the mixture were added water (30 mL) and the aqueous layer was separated off. The organic layer was concentrated under reduced pressure to give oily residue, which was purified by silica gel column chromatography (eluent: n-hexane/toluene) to afford 7.9 g of phenylindole as a viscous oil.

Workup

  1. customtwo-necked, round bottomed flask equipped a gas inlet
  2. customthe flask was evacuated
  3. additionfilled with nitrogen
  4. additionSubsequently, to the mixture was added dehydrated THF (11 mL)
  5. customto prepare a catalyst solution
  6. customthermometer, and a gas inlet was evacuated
  7. additionfilled with nitrogen
  8. customwas kept at 15° C.
  9. temperatureunder reflux
  10. temperatureAfter cooling the reaction mixture to room temperature
  11. customthe aqueous layer was separated off
  12. concentrationThe organic layer was concentrated under reduced pressure
  13. customto give oily residue, which
  14. customwas purified by silica gel column chromatography (eluent: n-hexane/toluene)

Sources & evidence

ORD record
ord-97c67e266a6c4a72955252e97ab10236
Source dataset
uspto-grants-2016_01
Patent number
US09233922B2

Reaction notes

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