Chlorotrimethylsilane → HCID 11492359, compound

HRID 1527841Notes

Reaction equation

HRID 1527841 reaction equation
P(N)([O-])[O-].[CH3:5][O:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[CH2:12])=[CH:9][CH:8]=1.[C:15]1(=[O:21])[CH2:20][CH2:19][CH2:18][CH:17]=[CH:16]1.C[Si](Cl)(C)C>CCOCC.C(Cl)Cl.[Cu].C1C=CC=CC=1>[CH3:5][O:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11][CH2:12][C@H:17]2[CH2:18][CH2:19][CH2:20][C:15](=[O:21])[CH2:16]2)=[CH:9][CH:8]=1

Participants

9

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 125074-MethoxystyreneHCID 135942-Cyclohexen-1-oneHCID 10080320Phosphoramidite

Product 1

HCID 11492359HCID 11492359, compoundYield 48%

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 241BenzeneSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

(C6H6) (10.1 mg, 0.02 mmol, 0.05 eq.) and the phosphoramidite ligand (21.6 mg, 0.040 mmol, 0.10 eq.) were dissolved in Et2O (2.0 mL) under an argon atmosphere and allowed to stir for 1 h at room temperature. In another flask, Cp2ZrHCl (206.0 mg, 0.80 mmol, 2.0 eq.) was added to a stirred, room temperature, solution of 4-methoxystyrene (0.13 mL, 1.0 mmol, 2.5 eq.) in CH2Cl2 (0.40 mL) under an argon atmosphere. After stirring for 15 min, the resulting clear red/orange solution was transferred via syringe over about 1 min to the stirred solution containing the copper and ligand under an argon atmosphere. The resulting black mixture was allowed to stir for an additional 10 minutes before cyclohexenone (39 μL, 0.40 mmol, 1.0 eq) and then TMSCl (0.26 mL, 2.0 mmol, 5.0 eq.) were added dropwise via syringe. Stirring continued at room temperature for 4 h before the reaction was quenched by the addition of Et2O (ca 3 mL) and then NH4Cl (1M aq., ca 1.5 mL). The mixture was partitioned between the aqueous and Et2O layers and the aqueous phase extracted with Et2O (3×10 mL). The combined organic phase was washed with NaHCO3 (aq. sat., ca 10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Flash column chromatography of the yellow residue (1:9 EtOAc/petrol; SiO2) gave (R)-3-(4-methoxyphenethyl)cyclohexanone (45 mg, 0.19 mmol, 48%) as a colourless oil. HPLC analysis indicated an enantiomeric excess of 90% [Chiralpak® IA; flow: 1 mL/min; hexane/i-PrOH: 90:10; λ=210 nm; minor enantiomer (S)-3-(4-methoxyphenethyl)-cyclohexanone, tR=11.4 minutes; major enantiomer (R)-3-(4-methoxyphenethyl)-cyclohexanone, tR=12.2 minutes]. 1H NMR (500 MHz, CDCl3) δH/ppm 1.33-1.44 (m, 1H) 1.55-1.71 (m, 3H) 1.81 (apparent tspt, J=11.03, 3.50 Hz, 1H) 1.92-1.99 (m, 1H) 2.02-2.10 (m, 2H) 2.27 (dddd, J=13.70, 12.50, 6.50, 1.40 Hz, 1H) 2.33-2.40 (m, 1H) 2.48 (ddt, J=13.75, 4.14, 1.93, 1.93 Hz, 1H) 2.58 (t, J=8.04 Hz, 2H) 3.79 (s, 3H) 6.83 (d, J=8.83 Hz, 2H) 7.09 (d, J=8.80 Hz, 2H); 13C NMR (126 MHz, CDCl3) δC/ppm 25.2, 31.2, 32.0, 38.4, 38.6, 41.5, 48.0, 55.2, 113.8 (2C), 129.1 (2C), 134.0, 157.8, 211.8; HRMS (ESI) m/z calcd for C16H20NaO2 [M+Na]+: 255.1356 found: 255.1349; [α]24589=−20.1 (c 1.03, CHCl3); IR (vmax/cm−1): 1710, 2933.

Workup

  1. stirringAfter stirring for 15 min
  2. waitthe resulting clear red/orange solution was transferred via syringe over about 1 min to the stirred solution
  3. stirringStirring
  4. waitcontinued at room temperature for 4 h before the reaction
  5. customwas quenched by the addition of Et2O (ca 3 mL)
  6. customThe mixture was partitioned between the aqueous and Et2O layers
  7. extractionthe aqueous phase extracted with Et2O (3×10 mL)
  8. washThe combined organic phase was washed with NaHCO3 (aq. sat., ca 10 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9151395c2ba541dc86ccd7b3a6cada8f
Source dataset
uspto-grants-2015_07
Patent number
US09090545B2

Reaction notes

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