2-(Di-tert-butylphosphino)biphenyl → 4,4,6,6-Tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-one

HRID 600373Notes

Reaction equation

HRID 600373 reaction equation
I[C:2]1[C:3](=[O:12])[C:4]([CH3:11])([CH3:10])[CH2:5][C:6]([CH3:9])([CH3:8])[CH:7]=1.[N+:13]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O)([O-:15])=[O:14].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:8][C:6]1([CH3:9])[CH2:5][C:4]([CH3:11])([CH3:10])[C:3](=[O:12])[C:2]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N+:13]([O-:15])=[O:14])=[CH:7]1

Participants

6

Reactant 4

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 2773548(2-Nitrophenyl)boronic acidHCID 121540932-Iodo-4,4,6,6-tetramethyl-cyclohex-2-en-1-oneHCID 17749109Barium hydroxide, octahydrate

Product 1

HCID 121540944,4,6,6-Tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-oneYield 70%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
38 °C

Procedure

A 250-mL modified Schlenk-type flask was charged with 2-iodo-4,4,6,6-tetramethyl-cyclohex-2-en-1-one (3, 1.06 g, 3.96 mmol, 1 equiv), 2-nitrophenyl boronic acid (661 mg, 3.95 mmol, 1.0 equiv), Pd2(dba)3 (181 mg, 0.198 mmol, 0.05 equiv), 2-(di-t-butylphosphino)-biphenyl (236 mg, 0.791 mmol, 0.20 equiv), and barium hydroxide octahydrate (3.73 g, 11.8 mmol, 3.0 equiv). Tetrahydrofuran (64 mL) and distilled water (13 mL) were added sequentially to the flask, and the resulting red, heterogeneous mixture was heated to 38° C. The progress of the reaction was monitored by thin-layer chromatography (20% ethyl acetate-hexanes, Rf=0.37, 0.61 for product, starting material, respectively; UV, CAM). After 1.5 h, the reaction was allowed to cool to 23° C., then was quenched by the addition of saturated aqueous ammonium chloride solution (30 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with brine (20 mL), and then were dried over sodium sulfate. Filtration and concentration of the dried organic layers afforded a brown oil which was purified by flash column chromatography (10% ethyl acetate-hexanes), to afford 4,4,6,6-tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-one (4, 755 mg, 70%) as a white solid. 4,4,6,6-Tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-one (4) could be further purified by re-crystallization from hot 10% ethyl acetate-hexanes solution (white crystals, mp 101-102° C.).

Workup

  1. distillationTetrahydrofuran (64 mL) and distilled water (13 mL)
  2. additionwere added sequentially to the flask
  3. temperatureto cool to 23° C.
  4. customwas quenched by the addition of saturated aqueous ammonium chloride solution (30 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (2×30 mL)
  7. washThe combined organic layers were washed with brine (20 mL)
  8. dry with materialwere dried over sodium sulfate
  9. filtrationFiltration and concentration of the dried organic layers
  10. customafforded a brown oil which
  11. customwas purified by flash column chromatography (10% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-b4461b9d9e89441cb470296f63b94cfe
Source dataset
uspto-grants-2011_03
Patent number
US07902196B2

Reaction notes

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