2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → (3R)-3-methyl-6-(prop-1-en-2-yl)-3,4-dihydro-1H-isochromen-1-one

HRID 1501958Notes

Reaction equation

[C:1]([Mg]Br)([CH3:3])=[CH2:2].Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[O:12][C@H:11]([CH3:18])[CH2:10]2.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH3:18][C@@H:11]1[CH2:10][C:9]2[C:14](=[CH:15][CH:16]=[C:7]([C:1]([CH3:3])=[CH2:2])[CH:8]=2)[C:13](=[O:17])[O:12]1

Participants

Conditions

Temperature: 0 °C

Procedure

A 0.5 molar solution of zinc chloride (1.696 g, 12.44 mmol) in dry THF (16.59 mL) was cooled to 0° C. A solution of isopropenylmagnesium bromide (24.89 mL, 12.44 mmol) was added via syringe. The reaction was stirred at 0° C. for 30 minutes before being cannulated into a sealed tube containing (3R)-6-bromo-3-methyl-3,4-dihydro-1H-isochromen-1-one (2.00 g, 8.30 mmol), PdOAc2 (0.093 g, 0.42 mmol), and X—PHOS (0.395 g, 0.830 mmol) in THF (16.6 mL) under N2 atmosphere. The tube was heated to 70° C. overnight. The reaction was then cooled and partitioned between water (100 mL) and EtOAc (220 mL). The organic layer was then washed with brine, dried over magnesium sulfate, filtered and concentrated. MPLC purification (10-50% EtOac/Hex) gave (3R)-3-methyl-6-(prop-1-en-2-yl)-3,4-dihydro-1H-isochromen-1-one:

Workup

custombefore being cannulated into a sealed tube
temperatureThe tube was heated to 70° C. overnight
temperatureThe reaction was then cooled
custompartitioned between water (100 mL) and EtOAc (220 mL)
washThe organic layer was then washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customMPLC purification (10-50% EtOac/Hex)

Sources & evidence

ORD record: ord-287c85a584e84c2bb447152dd826e36e
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206199B2

Reaction notes

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