Triphenylphosphine Oxide → (3R/S)-2,2-Dimethyl-3-(phenylmethoxy)pent-4-en-1-ol

HRID 1671398Notes

Reaction equation

HRID 1671398 reaction equation
[CH3:1][C:2]([CH3:5])([O-])[CH3:3].[K+].[PH5].O1[CH2:12][CH2:11][CH2:10][CH:9]1[OH:13].[C:14]1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:19]=CC=C[CH:15]=1.C([O:38]C)(C)(C)C.[CH3:40][CH2:41][CH2:42]CCC>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1.CCCCCC.C(OC)(C)(C)C>[CH3:1][C:2]([CH3:5])([CH:40]([O:13][CH2:9][C:10]1[CH:11]=[CH:12][CH:19]=[CH:14][CH:15]=1)[CH:41]=[CH2:42])[CH2:3][OH:38]

Participants

10

Reactant 5

HCID 13097Triphenylphosphine OxideHCID 93002Tetrahydro-2-hydroxyfuranHCID 21982663Methyl t-butylether hexaneHCID 23665647Potassium tert-butoxideHCID 178527699HCID 178527699, compound

Product 1

HCID 67348815(3R/S)-2,2-Dimethyl-3-(phenylmethoxy)pent-4-en-1-olYield 61%

Reagents, catalysts & solvents 4

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Following the general procedure for the methylenation of lactols by Wittig-olefination (Description 4, Method A), 100 g (280 mmol) of methyltriphenylphosphonium bromide was reacted overnight at room temperature with 270 mL (270 mmol) of a one molar (1.0 μl) solution of potassium tert-butoxide (KOtBu) in 350 mL of anhydrous tetrahydrofuran (THF). The phosphorane was subsequently reacted in situ at ca. 0° C. (icebath) with 29.7 g (134 mmol) of (2R/S)(3R/S)-4,4-dimethyl-3-phenylmethoxy)oxolan-2-ol (2b) dissolved in 150 mL of anhydrous tetrahydrofuran (THF). After work-up and isolation, followed by repeated titration of residual triphenylphosphine oxide (Ph3PO) with methyl tert-butyl ether (MTBE) and hexane (Hxn) mixtures, i.e. MTBE/Hxn˜1:2 (v/v) at ca. −20° C. (freezer), the crude product was obtained. Purification by silica gel column chromatography using ethyl acetate (EtOAc) and hexane (Hxn) mixtures as eluent (EtOAc/Hxn=1:4→EtOAc/Hxn=1:3→EtOAc/Hxn=1:2) provided 18.0 g (61% yield) of the title compound (2) as a colorless liquid. Rf=0.63 (EtOAc/Hxn=1:3). MS (ESI) m/z: 221.1 (M+H)+, 243.1 (M+Na)+. The analytical data was consistent with the proposed structure, to the corresponding material (1) obtained starting from enantiopure D-pantolactone, and with the data reported in the literature (Mandel et al., Org. Lett. 2004, 6(26), 4801-4803; and Ito et al., Synthesis 1993, 137-140).

Workup

  1. customat ca. −20° C.
  2. customthe crude product was obtained
  3. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-7829216d952a40ce9616b21bc5f9ab9c
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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