Unexpected Lewis Acid Mediated Reactions of 1-Arylbut-3-en-1-ols with Trimethyl Orthoformate - A New Synthesis of Homoallyl Ethers and Chlorides

Abstract

1-Arylbut-3-en-1-ols react with trimethyl orthoformate in the presence of Lewis acids like InCl₃, BiCl₃, TiCl₄, or BF₃·OEt₂ providing homoallyl ethers or homoallyl chlorides in high yields.

Key words

alcohols - ethers - indium - halides - Lewis acids

References and Notes

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Similar results were obtained when 1a was reacted with triethyl orthoformate (TEOF).

16

General Procedure for InCl ₃ -Mediated Reactions of Homoallyl Alcohols 1 with TMOF (2)
InCl₃ (3 mmol) was added to a stirred solution of homoallyl alcohol 1 (3 mmol) and TMOF (2, 3 mmol) in CH₂Cl₂ (25 mL). The reaction mixture was stirred at r.t. under Ar until 1 had been completely consumed (TLC). Then H₂O (25 mL) was added and the resulting mixture was extracted with CH₂Cl₂ (75 mL). The extracts were washed with brine (25 mL), dried over MgSO₄, filtered and concentrated in vacuo. The products were purified by Kugelrohr distillation or flash chromatography on silica gel.

17

Selected data for 3e: R _f = 0.20 (PE-CH₂Cl₂, 7:3). UV/Vis (MeCN): λ_max (log ε) = 269 (3.17), 277 (3.18) nm. IR (ATR): 3090, 2927, 2819, 1641 (C=C), 1500, 1448, 1357, 1189, 1156, 1108 (C-O-C), 1091, 974, 912, 808, 729 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.33 (s, 3 H, 2′-CH₃), 2.38 (s, 3 H, 5′-CH₃), 2.44 (br ddd, 1 H, ^² J _gem = 14.5 Hz, ^³ J = ca. 7.4 Hz, ^³ J = ca. 7.4 Hz, 2-H), 2.53 (br ddd, 1 H, ^² J _gem = 14.5 Hz, ^³ J = ca. 7.0 Hz, ^³ J = ca. 7.0 Hz, 2-H), 3.27 (s, 3 H, 1-OCH₃), 4.48 (br dd, ^³ J = 7.9 Hz, ^³ J = 8.0 Hz, 1 H, 1-H), 5.11 (ddt, 1 H, ^³ J _cis = 9.8 Hz, ^² J = 1.3 Hz, 4-H), 5.17 (dq, 1 H, ^³ J _trans = 17.2 Hz, ^² J = 1.3 Hz, 4-H), 5.87 (dddd, 1 H, ^³ J _cis = 10.1, ^³ J _trans = 17.1 Hz, ^³ J = ca. 7.0 Hz, ^³ J = ca. 7.0 Hz, 3-H), 7.04 (br d, ³ J = 7.5 Hz, 1 H, 3′-H), 7.08 (br d, ³ J = 7.8 Hz, 1 H, 4′-H), 7.24 (s, 1 H, 6-H). ¹³C NMR (75 MHz, CDCl₃): δ = 18.7 (2′-CH₃), 21.1 (5′-CH₃), 41.6 (C-2), 56.6 (1-OCH₃), 80.0 (C-1), 116.6 (C-4), 126.4 (C-6′), 127.8 (C-4′), 130.2 (C-3′), 132.2 (C-1′), 135.2 (C-3), 135.6 (C-5′), 139.5 (C-1′). MS (EI, 70 eV): m/z (%) = 149 (100) [M⁺ - 41], 143 (12), 133 (45), 119 (59), 105 (65), 103 (15), 91 (31), 77 (32), 65 (8), 51 (10). HRMS (EI): m/z calcd for C₁₃H₁₈O: 190.1357; found: 190.1316 [M⁺]. Anal. Calcd for C₁₃H₁₈O: C, 82.06; H, 9.53. Found: C, 82.05; H, 9.58.

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Selected data for 4f: R _f = 0.62 (PE-CH₂Cl₂, 7:3). UV/Vis (MeCN): λ_max (log ε) = 271 (3.01), 265 (3.05) nm. IR (ATR): 3077, 2980, 2905, 1641 (C=C), 1604, 1508, 1431, 1343, 1295, 1220, 1156, 1073 (C-O-C), 1013, 991, 915, 831, 785, 722 cm^-1. MS (EI, 70 eV): m/z (%) = 273 (4) [M⁺ - 41], 150 (20), 149 (100), 109 (35), 95 (3), 53 (2). HRMS (EI): m/z calcd for the fragment [C₁₀H₁₀F⁺]: 149.0761; found: 149.0750.

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Selected data for 5j: R _f = 0.50 (PE). UV/Vis (MeCN): λ_max (log ε) = 266 (1.97) nm. IR (ATR): 3080, 2980, 1654 (C=C), 1523, 1501, 1449, 1424, 1359, 1316, 1148, 1130, 1042, 991, 955, 928, 802, 761, 741, 684 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 2.96 (br ddd, 1 H, ^² J = 14.3 Hz, ^³ J = ca. 7.8 Hz, ^³ J = ca. 7.8 Hz, 2-H), 3.05 (br ddd, 1 H, ^² J = 14.3 Hz, ^³ J = ca. 7.1 Hz, ^³ J = ca. 7.1 Hz, 2-H), 5.15 (ddt, 1 H, ^³ J = 10.1 Hz, ^² J = 1.4 Hz, ⁴ J = 1.2 Hz, 4-H), 5.19 (dq, 1 H, ^² J = 1.4 Hz, ^³ J _trans = 17.1 Hz, 4-H), 5.22 (br dd, 1 H, ^³ J = ca. 8.0 Hz, ^³ J = ca. 8.0 Hz, 1-H), 5.73 (dddd, 1 H, ^³ J _trans = 17.2 Hz, ^³ J _cis = 10.1 Hz, ^³ J = ca. 7.0 Hz, ^³ J = ca. 7.0 Hz, 3-H). ¹³C NMR (125 MHz, CDCl₃): δ = 41.1 (C-2), 49.5 (C-1), 114.5 (C-1′), 119.5 (C-4), 132.5 (C-3) 138.7 (d, C-4′), 141.2 (d, C-3′and C-5′), 144.75 (d, C-2′and C-6′). MS (EI, 70 eV): m/z (%) = 256 (33) [M⁺], 215 (100) [M⁺ - 41], 207 (57), 194 (35), 181 (45), 151 (12), 143 (11), 123 (7), 105 (3), 99 (6), 75 (5), 51 (5). HRMS (EI): m/z calcd for C₁₀H₆ClF₅: 256.0078; found: 256.0076 [M⁺].

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Compound 4f (D₁): ¹H NMR (500 MHz, CDCl₃): δ = 2.34 (dddq, 1 H, ^² J = 13.9 Hz, ^³ J = ca. 6.5 Hz, ^³ J = ca. 6.5 Hz, ⁴ J = 1.1 Hz, 2-H), 2.55 (br dddt, 1 H, ^² J = 14.0 Hz, ^³ J = ca. 7.2 Hz, ^³ J = ca. 7.2 Hz, ⁴ J = 1.3 Hz, 2-H), 4.08 (dd, 1 H, ^³ J = 7.3 Hz, ^³ J = 6.6 Hz, 1-H), 4.96 (dddd, 1 H, ^³ J _trans = 17.2 Hz, ^² J = ca. 1.6 Hz, ⁴ J = ca. 1.6 Hz, ⁴ J = ca. 1.6 Hz, 4-H), 4.98 (br d, 1 H, ^³ J _cis = 10.4 Hz, 4-H), 5.67 (dddd, 2 H, ^³ J _trans = 17.1 Hz, ^³ J _cis = 10.2 Hz, ^³ J = ca. 6.9 Hz, ^³ J = ca. 6.9 Hz, 3-H), 7.06 (br dd, 2 H, ^³ J = 8.7 Hz, ^³ J _H-F = 8.0 Hz, 3′-H and 5′-H), 7.23 (br dd, 2 H, ^³ J = 8.7 Hz, ⁴ J _H-F = 5.5 Hz, 2′-H and 6′-H). ¹³C NMR (125 MHz, CDCl₃): δ = 43.05 (C-2), 77.85 (C-1), 115.44 (d, ^² J _C-F = 21.4 Hz, C-3′ and C-5′), 117.28 (C-4), 128.88 (d, ^³ J _C-F = 8.5 Hz, C-2′ and C-6′), 134.7 (C-3), 137.70 (d, ⁴ J _C-F = 2.9 Hz, C-1′), 162.5 (d, ^¹ J _C-F = 245.5 Hz, C-4′).
Compound 4f (D₂): ¹H NMR (500 MHz, CDCl₃): δ = 2.47 (dddq, 1 H, ^² J = 14.1 Hz, ^³ J = ca. 7.1 Hz, ^³ J = ca. 7.1 Hz, ⁴ J = 1.1 Hz, 2-H), 2.62 (dddt, 1 H, ^² J = 14.1 Hz, ^³ J = ca. 7.1 Hz, ^³ J = ca. 7.1 Hz, ⁴ J = 1.2 Hz, 2-H), 4.39 (dd, 1 H, ^³ J = ca. 6.4 Hz, ^³ J = ca. 6.4 Hz, 1-H), 5.04 (br d, 1 H, ^³ J _cis = 10.0 Hz, 4-H), 5.05 (dddd, 1 H, ^³ J _trans = 17.5 Hz, ^² J = ca. 1.6 Hz, ⁴ J = ca. 1.6 Hz, ^² J = ca. 1.6 Hz, 4-H), 5.77 (dddd, 2 H, ^³ J _trans = 16.9 Hz, ^³ J _cis = 10.5 Hz, ^³ J = ca. 7.2 Hz, ^³ J = ca. 7.2 Hz, 3-H), 6.94 (br dd, 2 H, ^³ J = ca. 8.8 Hz, ^³ J _H-F = ca. 8.8 Hz, 3′-H and 5′-H), 7.14 (br dd, 2 H, ^³ J = 8.6 Hz, ⁴ J _H-F = 5.5 Hz, 2′-H and 6′-H). ¹³C NMR (125 MHz, CDCl₃): δ = 41.96 (C-2), 79.4 (C-1), 115.06 (d, ^² J _C-F = 21.3 Hz, C-3′and C-5′), 117.54 (C-4), 128.51 (d, ^³ J _C-F = 7.5 Hz, C-2′ and C-6′), 134.5 (C-3), 137.19 (d, ⁴ J _C-F = 3.7 Hz, C-1′), 162.20 (d, ^¹ J _C-F = 244.7 Hz, C-4′).