HCID 178418573, compound → HCID 131720241, compound

HRID 1489202Notes

Reaction equation

HRID 1489202 reaction equation
[CH3:1][Mg]Br.[C:4]([C:8]1[C:13]([O:14][SiH:15]([CH3:17])[CH3:16])=[C:12]([Br:18])[C:11]([O:19][CH3:20])=[CH:10][C:9]=1[CH2:21][CH:22]1[C:27](=[O:28])[CH:26]=[CH:25][CH2:24][C:23]1([CH3:30])[CH3:29])([CH3:7])([CH3:6])[CH3:5]>CCOCC.[Cu]I>[C:4]([C:8]1[C:13]([O:14][SiH:15]([CH3:16])[CH3:17])=[C:12]([Br:18])[C:11]([O:19][CH3:20])=[CH:10][C:9]=1[CH2:21][C@H:22]1[C:23]([CH3:30])([CH3:29])[CH2:24][C@@H:25]([CH3:1])[CH2:26][C:27]1=[O:28])([CH3:7])([CH3:5])[CH3:6]

Participants

5

Reactant 2

HCID 178418573HCID 178418573, compoundHCID 178488804HCID 178488804, compound

Product 1

HCID 131720241HCID 131720241, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of copper(I) iodide (2 mg) in 1 mL of anhydrous ether at 0°C. was added methylmagnesium bromide (0.106 mL of a 3.0 M solution in ether, 0.319 mmol, 1.00 equiv). Then enone 13 (149 mg, 0.319 mmol) in 2 mL of anhydrous ether was added slowly to the stirring cuprate mixture at a temperature maintained below 5° C., and upon completion of the addition, the reaction mixture was stirred at 0° C. for 3 h before quenching with a 4:1 mixture of saturated aqueous NH4Cl/NH4OH. The resultant biphasic mixture was extracted with ether, dried over Na2SO4, and concentrated under diminished pressure. Purification by flash column chromatography (silica gel, hexanes/ethyl acetate, 9:1) afforded 36 mg (30%) of the desired conjugate addition product as a white solid. 1H NMR (400 MHz, CDCl3) δ0.22 (s, 6H, Si(CH3)2), 1.00 [m, 18H, 3,3,5-CH3 and SiC(CH3)3 ], 1.50 (dd, 2H, J=15.1, 6.5 Hz, 4-Hz, 4-H), 2.02 (m, 1H, 5-H), 2.14 and 2.23 (ABq, 2H, JAB =12.0 Hz, 6-H), 2.42 (dd, 1H, J=10.4, 6.4 Hz, 2-H), 2.88 and 2.89 (d of ABq, 2H, JAB =12.0 Hz, JA =10.4 Hz, JB =6.3 Hz, benzylic-CH2), 3.82 (s, 3H, OCH3), 6.65 (s, 1H, 6'-H), 6.92 ppm (s, 1H, 3'-H).

Workup

  1. temperaturemaintained below 5° C.
  2. additionupon completion of the addition
  3. custombefore quenching with a 4:1 mixture of saturated aqueous NH4Cl/NH4OH
  4. extractionThe resultant biphasic mixture was extracted with ether
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under diminished pressure
  7. customPurification by flash column chromatography (silica gel, hexanes/ethyl acetate, 9:1)
  8. customafforded 36 mg (30%) of the desired
  9. additionconjugate addition product as a white solid

Sources & evidence

ORD record
ord-363506515c1742959cd60c8c8309434b
Source dataset
uspto-grants-1997_10
Patent number
US05677336

Reaction notes

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