Chemoselective Isomerization of Secondary-Type Propargylic Alcohols to Propargylic/Allenic Bromides, and Brominated Dienes with Appel-Type Reaction Conditions

Abstract

Herein is described the chemoselective isomerization of secondary-type propargylic alcohols to allenic bromides, propargylic bromides and brominated dienes under Appel-type reaction conditions containing Ph₃P, CBr₄ and additives.

Key words

Appel reaction - propargylic alcohol - allene - diene - isomerization

References and Notes

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• 15 When the same reaction was conducted with CCl₄ instead of CBr₄, the corresponding chlorinated allene derivative was obtained in 40% yield. For a selected paper on the S_N2-type chlorination of a primary alcohol using CCl₄ and PPh₃, see: Lee JB. Downie IM. Tetrahedron  1967,  23:  359 
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13

General Procedure for the Synthesis of Allene Derivatives 2: CBr₄ (331 mg, 1.0 mmol), Ph₃P (262 mg, 1.0 mmol), propargylic alcohol 1 (0.50 mmol), i-Pr₂NEt (129 mg, 1.0 mmol), P(n-Bu)₃ (10 mg, 0.05 mmol), and a freshly distilled toluene (1 mL) were successively added into a screw-capped vial, and the vial was sealed with a cap containing a PTFE septum. The reaction mixture was stirred at 100 ˚C, and monitored by TLC until the propargylic alcohol 1 was consumed. To quench the reaction, H₂O (2 mL) was added to the mixture. The mixture was extracted with CH₂Cl₂ (3 ×), and the combined organic extracts were dried over Na₂SO₄, filtered, and then evaporated under reduced pressure. The crude product was purified by silica gel chromatography(hexane) to produce the allene derivative 2, and if necessary, was further purified by a recycling preparative HPLC equipped with a GPC column (chloroform as an eluent). Spectral data for selected compound: 1-(3-Bromo-1,2-nonadien-1-yl)benzene (2a): pale yellow oil. ^¹H NMR (300 MHz, CDCl₃): δ = 0.86 (t, 3 H, J = 7.2 Hz), 1.24-1.38 (m, 6 H), 1.50 (quint, 2 H, J = 7.2 Hz), 2.52 (td, 2 H, J = 7.2, 3.0 Hz), 6.19 (t, 1 H, J = 3.0 Hz), 7.23-7.27 (m, 1 H), 7.32-7.33 (m, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 13.9, 22.5, 27.9, 28.2, 31.4, 38.0, 96.1, 100.3, 127.7, 128.1, 128.7, 133.0, 199.8. MS (FAB): m/z (%) = 281 (100) [M⁺], 279 (40) [M⁺]. HRMS (FAB): m/z calcd for C₁₅H₂₀Br: 279.0748; found: 279.0726.

16

General Procedure for the Synthesis of Diene Derivatives 3: The same procedure as above without i-Pr₂NEt gave the diene derivative 3. However, formation of a quite small amount of the (1Z,3E)-diene along with the (1E,3E)-diene separable by column chromatography was observed by NMR. Spectral data for selected compound: [(1E,3E)-3-Bromo-1,3-nonadien-1-yl]benzene (3a): pale brown oil. ^¹H NMR (300 MHz, CDCl₃): δ = 0.88 (t, 3 H, J = 7.2 Hz), 1.27 (m, 3 H), 1.35 (m, 1 H), 1.47 (m, 2 H), 2.35 (q, 2 H, J = 7.2 Hz), 6.08 (t, 1 H, J = 7.2 Hz), 6.73 (d, 1 H, J = 15.0 Hz), 6.89 (d, 1 H, J = 15.0 Hz), 7.23 (m, 1 H), 7.30 (m, 2 H), 7.42 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 13.9, 22.4, 28.1, 31.4, 31.7, 126.7, 126.9, 127.7, 127.9, 128.6, 128.7, 132.1, 135.3. MS (EI): m/z = 279 [M⁺]. HRMS (FAB): m/z calcd for C₁₅H₂₀Br: 279.0748; found: 279.0728. Stereochemistry (1E,3E) of the isolated compound was determined by
the chemical shift and coupling constant of the related compound. Specific peaks derived from (1Z,3E)-diene 3a were observed by ^¹H NMR. ^¹H NMR: δ = 5.87 (t, 1 H, J = 7.2 Hz), 6.76 (d, 2 H, J = 15.0 Hz), 6.94 (d, 1 H, J = 15.0 Hz). Other peaks overlapped with those of the (1E,3E)-diene.

17

We have no clear cause for the low yield of diene derivative 3; however, formation of several complex products, which were probably derived from the starting propargylic alcohol, was observed by an NMR measurement.