Remote Functionalization in Nicholas Reactions of Vinylogous γ-Carbonyl Cations

Abstract

The Nicholas reactions of Co₂(CO)₆ complexes of allyl/propargyl alcohol–ynoates and ynone ethylene acetals give selective to exclusive reaction with nucleophiles at the site ε to the carbonyl or carbonyl equivalent. For nucleophiles giving modest selectivity in the above cases, the analogous Nicholas reactions may be accomplished with propargyl acetate–Co₂(CO)₆ complexes of conjugated enynoates, to give complex ε selectivity.

Key words

umpolung - carbocation - alkyne complexes - Lewis acids - condensation

• References and Notes


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• 16 For the preparation of compounds 7–10, see Supporting Information.
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• 18 Excess BF₃·OEt₂ slowly afforded a mixture of products of attack ε (11a) and γ (11a′) to the carbonyl.
• 19 General Procedure A To a solution of 7 (0.0873 g, 0.198 mmol) and MeOH (8.0 μL, 0.60 mmol) in CH₂Cl₂ (9 mL, 3.0 equiv) at 0 °C was added Bu₂BOTf (0.20 mL of a 1.0 M solution, 0.20 mmol). After 30 min, NH₄Cl (aq) was added, and the mixture subjected to a conventional extractive workup (CH₂Cl₂). Following flash chromatography (PE–Et₂O, 25:1), 11a was isolated as a red-brown viscous liquid (0.0677 g, 75%).
• 20 Amiralaei S, Gauld J, Green JR. Chem. Eur. J. 2011; 17: 4157
• 21 Selected Characterization Data (for complete data, see Supporting Information) Compound 11a: IR (neat): 2984, 2099, 2060, 2023, 1704 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 6.77 (dt, J = 15.1, 1.6 Hz, 1 H), 6.31 (dt, J = 15.1, 5.4 Hz, 1 H), 4.32 (q, J = 7.1 Hz, 2 H), 4.04 (dd, J = 5.4, 1.6 Hz, 1 H), 3.39 (s, 3 H), 1.33 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 198.1, 169.7, 134.4, 127.1, 88.6, 78.5, 72.2, 62.0, 58.2, 14.1. MS: m/e 426 [M⁺ – CO], 398 [M⁺ – 2CO], 370 [M⁺ – 3CO], 342 [M⁺ – 4CO], 314 [M⁺ – 5CO], 286 [M⁺ – 6CO]. HRMS: m/z calcd for C₁₅H₁₂Co₂O₉ [M⁺ –CO]: 425.9196; found: 425.9193. Compound 13b: IR (neat): 2968, 2088, 2046, 1998 cm^–1. ¹H NMR (300 MHz, CDCl₃): 6.60 (d, J = 14.7 Hz, 1 H), 6.01 (dt, J = 14.7, 6.7 Hz, 1 H), 5.80 (m, 1 H), 4.95–5.08 (m, 2 H), 4.18 (m, 2 H), 4.05 (m, 2 H), 2.30 (m, 2 H), 2.23 (m, 2 H), 1.09 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 198.8, 137.5, 127.3, 115.7, 115.3, 98.7, 92.3, 66.4, 42.5, 33.4, 32.2, 26.0. MS: m/e = 492 [M⁺ – CO], 464 [M⁺ – 2CO], 436 [M⁺ – 3CO], 408 [M⁺ – 4CO], 380 [M⁺ – 5CO], 352 [M⁺ – 6CO]. HRMS: m/z calcd for C₂₁H₂₂Co₂O₈ [M⁺ – 3CO]: 436.0131; found: 436.0121. Compound 14c: IR (neat): 2930, 2096, 2056, 2018, 1669 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 6.61 (app. t, J = 2.2 Hz, 1 H), 6.56 (dt, J = 15.0, 1.4 Hz, 1 H), 6.37 (dt, J = 15.0, 6.4 Hz, 1 H), 6.09 (app. t, J = 3.1 Hz, 1 H), 5.93 (m, 1 H), 3.54 (s, 3 H), 3.48 (d, J = 6.5 Hz, 2 H), 2.74 (t, J = 7.3 Hz, 2 H), 1.73 (m, 2 H), 1.27–1.40 (m, 6 H), 0.91 (t, J = 6.8 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 203,2, 198.2, 136.2, 129.4, 126.8, 122.0, 106.9, 106.8, 90.5, 87.8, 43.7, 33.6, 31.6, 30.3, 28.8, 24.6, 22.5, 14.0. MS: m/e = 487 [M⁺ – 2CO], 459 [M⁺ – 3CO], 431 [M⁺ – 4CO], 403 [M⁺ – 5CO], 375 [M⁺ – 6CO]. HRMS: m/z for C₂₃H₂₃Co₂NO₇ [M⁺ – 2CO]: 487.0240; found: 487.0258. Compound 15b: mp 71–72.5 °C. IR (neat): 2941, 2087, 2048, 2015, 1721 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.03 (d, J = 11.5 Hz, 1 H), 6.13 (s, 2 H), 5.90 (d, J = 11.5 Hz, 1 H), 4.27 (s, 2 H), 4.22 (q, J = 7.1 Hz, 2 H), 3.82 (s, 3 H), 3.78 (s, 6 H), 1.31 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ =199.5, 165.2, 160.2, 158.8, 142.3, 118.1, 108.7, 103.3, 92.7, 89.8, 82.0, 60.1, 55.2, 54.7, 27.3, 14.2. MS: m/e = 534 [M⁺ – 2CO], 506 [M⁺ – 3CO], 478 [M⁺ – 4CO], 450 [M⁺ – 5CO], 422 [M⁺ – 6CO]. HRMS: m/z calcd for ­C₂₃H₂₀Co₂O₁₁ [M⁺ – 4CO]: 477.9873; found: 477.9873.
• 22 The acetate was chosen due to concerns regarding the Lewis acid causing acidic media with an alcohol function, possibly resulting in alkene isomerization.
• 23 Sample Decomplexation To a solution of 11d (0.1042 g) in acetone at –78 °C was added CAN (0.55 g). The solution was warmed from –78 °C to –30 °C over 1 h and stirred at –30 °C for 2 h. NaCl (aq) was added, and the mixture was subjected to a conventional extractive workup (Et₂O). Preparative TLC (hexanes–Et₂O, 25:1) gave 16 as a 95:5 mixture of C-2/C-3 thiophene-substitution regioisomers (0.0406 g, 90%), as a colorless oil. IR (neat): 2982, 2213, 1701 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.18 (dd, J = 5.1, 1.1 Hz, 1 H), 6.96 (dd, J = 5.1, 3.5 Hz, 1 H), 6.62 (m, 1 H), 6.63 (dt, J =15.9, 6.7 Hz, 1 H), 5.66 (dt, J = 15.9, 3.3 Hz, 1 H), 4.24 (q, J = 7.1 Hz, 2 H), 3.70 (d, J = 6.7 Hz, 2 H), 1.32 (t, J = 7.1 Hz, 3 H); resonances from the C-3 isomer can be observed at 7.30 (dd, J = 4.9, 2.9 Hz, 1 H), 6.90 (dd, J = 4.9, 1.2 Hz, 1 H), 5.60 (dt, J = 15.9, 3.4 Hz, 1 H), 3.52 (d, J = 6.8 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 153.9, 148.5, 139.7, 127.1, 125.5, 124.4, 108.6, 84.5, 80.5, 61.9, 33.3, 14.0. HRMS: m/z calcd for C₁₂H₁₂O₂S [M⁺ – Et]: 191.0167; found: 191.0168.