Tetrahydrofuran → (3S)-2,2-Dimethyl-3-(phenylmethoxy)pent-4-en-1-ol

HRID 1671397Notes

Reaction equation

HRID 1671397 reaction equation
[CH3:1][C:2]([CH3:5])([O-])[CH3:3].[K+].[PH5].C(=O)=[O:9].[CH:11](O)([CH3:13])[CH3:12].O1[CH2:19][CH2:18][CH2:17][CH:16]1[OH:20].O1C[CH2:24][CH2:23][CH2:22]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][C:2]([CH3:5])([C@@H:12]([O:20][CH2:16][C:17]1[CH:18]=[CH:19][CH:24]=[CH:23][CH:22]=1)[CH:11]=[CH2:13])[CH2:3][OH:9]

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 93002Tetrahydro-2-hydroxyfuranHCID 23665647Potassium tert-butoxideHCID 86586944Isopropanol carbon dioxideHCID 178527699HCID 178527699, compound

Product 1

HCID 10998568(3S)-2,2-Dimethyl-3-(phenylmethoxy)pent-4-en-1-olYield 58%

Reagents, catalysts & solvents 1

HCID 74505Methyltriphenyliphosphonium bromideCatalyst

Procedure

Following the general procedure for the methylenation of lactols via Wittig-olefination (Description 4, Method A), 408 g (1.14 mmol) of freshly powdered methyltriphenylphosphonium bromide was reacted for six hours at room temperature with 1.1 L (1.1 mol) of a one molar (1.0 M) solution of potassium tert-butoxide (KOtBu) in 1 L of anhydrous tetrahydrofuran (THF). The phosphorane was subsequently reacted in situ at ca. −78° C. (dry ice/isopropanol bath) with 84.6 g (381 mmol) of (2R/S)(3R)-4,4-dimethyl-3-phenylmethoxy)oxolan-2-ol (1b) dissolved in 200 mL of anhydrous tetrahydrofuran (THF). After work-up and isolation, the crude product was purification in four portions by silica gel column chromatography using ethyl acetate (EtOAc) and n-heptane (Hptn) mixtures as eluent (EtOAc/Hptn=1:4) to provided 48.6 g (58% yield) of the title compound (1) as a colorless oil. Rf=0.35 (EtOAc/Hxn=1:4); 0.19 (EtOAc/Hxn=1:6). 1H NMR (400 MHz, CDCl3): δ=0.91 (s, 3H), 0.92 (s, 3H), 2.83 (t, J=6.0 Hz, 1H), 3.38 (dd, J=10.8, 6.0 Hz, 1H), 3.55 (dd, J=10.8, 6.4 Hz, 1H), 3.63 (d, J=8.4 Hz, 1H), 4.31 (d, J=12.0 Hz, 1H), 4.62 (d, J=11.6 Hz, 1H), 5.26 (ddd, J=17.0, 2.0, 0.8 Hz, 1H), 5.38 (ddd, J=10.6, 1.6, 0.8 Hz, 1H), 5.81 (ddd, J=17.2, 10.4, 8.4 Hz, 1H), 7.27-7.38 (m, 5H) ppm. MS (ESI) m/z: 221.1 (M+H)+. The analytical data was consistent with the proposed structure 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. custompurification in four portions by silica gel column chromatography

Sources & evidence

ORD record
ord-32f631d8e22442b0964d6f2e8e2cc240
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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