A High Yielding One-Pot Synthesis of Allylic-Vinylic Alcohols: The Adducts of Tetraallylstannane and α,β-Unsaturated Carbonyl Compounds

Abstract

The reaction of α,β-unsaturated aldehydes with tetra­allystannane (1, 0.25 equivalents) results in regioselective 1,2-addition to generate the corresponding allylic-vinylic alcohols in good to excellent yields (> 90%). Reactions with the equivalent ketones also proceed well (15-91%) although requiring more forcing conditions. Under these conditions, a second reaction pathway was evident for ketones that were less substituted at C3, namely that of methanolysis at C3. In all instances these reactions are elegant in their simplicity and show high levels of atom efficiency not typically found in similar methodologies for the synthesis of allylic-vinylic alcohols.

α,β-unsaturated carbonyl compounds - tetraallystannane - allylic-vinylic alcohols

References

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10

Experimental: Tetraallylstannane(1) was purchased from Aldrich. Experiments were conducted in d ₄-MeOH (Aldrich). NMR spectra were recorded on a Bruker Avance 300 MHz instrument. Chemical shifts are recorded in ppm and signal multiplicities have been assigned by DEPT experiments. Mass spectra were recorded using a Shimadzu QP5054 GCMS instrument. Comparison with literature values previously reported was carried out for compounds 3a, [10] 3b, [11] 3c, [14] 3d, [15] 3e, [16] 3f, [17] 3h, [14] and 3i. [18] Spectral data for other compounds is reported below.
General procedure for the allylation of α,β-unsaturated aldehydes using 1. A solution of the α,β-unsaturated aldehyde (1 mmol) and tetraallylstannane (60 µL, 0.25 mmol) in d ₄-MeOH (0.7 mL) was left at 25 ºC overnight. The reaction mixture was then poured onto water (10 mL) and extracted with CH₂Cl₂ (3 ¥ 10 mL). The combined organic extracted were dried over MgSO₄, filtered and the solvent removed under reduced pressure to afford the desired allylic-vinylic alcohol in excellent yield (Table [1] ).
General procedure for the allylation of α,β-unsaturated ketones using 1. A solution of the α,β-unsaturated ketone (1 mmol) and tetraallylstannane (60 µL, 0.25 mmol) in d ₄-MeOH (0.7 mL) was refluxed (reaction times for ketones varied from 12-216 h). The reaction mixture was then poured onto water (10 mL) and extracted with CH₂Cl₂ (3 ¥ 10 mL). The combined organic extracted were dried over MgSO₄, filtered and the solvent removed under reduced pressure to afford the desired allylic-vinylic alcohol in excellent yield (Table [2] ). To isolate by-products, the reaction was scaled up to 20 mmol of ketone. Products 3c, 3e, 3f, and 3g were then purified by Kugelrohr distillation (0.1 mmHg).
4-Hydroxy-4,5-dimethylhepta-1,5-diene (3g)
¹H NMR (MeOH-d ₄): δ 1.22 (3 H, s, CH₃), 1.57 (3 H, d, J = 7.0 Hz, H7), 1.58 (3 H, d, J = 0.8 Hz, CH₃), 2.01 (1 H, br, s, OH), 2.19 (1 H, dd, J = 13.9 Hz, 8.1 Hz, H3′), 2.36 (1 H, dd, J = 13.8 Hz, 6.5 Hz, H3), 5.00 (1 H, d, J = 3.6 Hz, H 1′), 5.05 (1 H, br s, H1), 5.50 (1 H, dq, J = 6.6 Hz, 0.9 Hz, H6), 5.63 (1 H, m, H2). ¹³C NMR (MeOH -d ₄): δ 12.5, 13.1 (2 ¥ CH₃), 26.8 (CH₃), 44.9 (CH₂, C3), 74.6 (C, C4), 117.3 (CH, C6), 118.1 (CH₂, C1), 134.0 (CH, C2), 140.0 (C, C5). EI m/z (%) [M⁺ - 41] 99 (68), 79 (21), 55 (51), 43 (100).
6-Allyl-6-hydroxy-4,8-dimethyl-bicyclo-[3.3.1]nona-3,7-diene-2-ketone (3j)
¹H NMR (CDCl₃): δ 1.69 (3 H, s, H11), 1.97 (1 H, br s, OH), 2.05 (3 H, s, H10), 2.08 (1 H, dt, J = 12.9 Hz, 3.0 Hz, H9, partially obscured), 2.19 (1 H, dt, J = 12.9 Hz, 3.0 Hz, H9′), 2.47 (2 H, m, H12, H12′), 2.59 (2 H, m, H4 + H8), 5.18 (2 H, m, H14, H14′), 5.21 (1 H, s, H6), 5.74 (1 H, s, H2), 5.95 (1 H, td, J = 17.2 Hz, 7.5 Hz, H13). ¹³C NMR (CDCl₃): δ 21.8 (CH₃, C11), 26.7 (CH₃, C10), 32.1 (CH₂, C9), 43.7 (CH, C4), 46.8 (CH₂, C12), 47.9 (CH, C8), 72.6 (C, C5), 119.5 (CH₂, C14), 124.4 (CH, C2), 127.9 (CH, C6), 133.4 (CH, C13), 134.9 (C, C7), 164.1 (C, C3), 198.2 (C, C1). EI m/z (%) [M⁺ - 41] 177 (100), 159 (57), 121 (28), 91 (31), 69 (51), 55 (23), 41 (58).
1-Allyl-1-hydroxy-3-methoxycyclohexane (4c)
¹H NMR (300 MHz, CDCl₃): δ 0.94-1.28 (3 H, m), 1.46-1.60 (3 H, m), 1.86-2.06 (2 H, m), 2.18 (2 H, d, J = 7.5 Hz, -CH ₂CH=CH₂), 3.28 (3 H, s, OCH₃), 3.41 (1 H, tt, J = 10.9 Hz, 4.2 Hz, H3), 4.98-5.11 (2 H, m, -CH₂CH=CH ₂), 5.75-5.89 (1 H, m, -CH₂CH=CH₂). ¹³C NMR (CDCl₃): δ 20.6, 32.5, 36.9 (CH₂, C4, C5, C6), 43.0 (CH₂, -CH₂CH=CH₂), 50.3 (CH₂, C2), 55.7 (CH₃, OCH₃), 72.4 (C, C1), 76.3 (CH, C3), 118.3 (CH₂, -CH₂CH=CH₂), 135.3 (CH, -CH₂ CH= CH₂). EI m/z (%) [M⁺ - 41] 129 (40), 97 (85), 69 (82), 55 (50), 41 (100).
4-Ethyl-4-hydroxy-6-methoxy-hex-1-ene (4e)
¹H NMR (MeOH-d ₄): δ 0.85 (3 H, t, J = 7.4 Hz, -CH ₂CH₃), 1.45 (2 H, q, J = 7.4 Hz, -CH₂CH ₃), 1.69 (2 H, t, J = 7.1 Hz), 2.19 (2 H, d, J = 7.3 Hz), 3.28 (3 H, s, OCH₃), 3.49 (2 H, t, J = 7.1 Hz), 4.95-5.05 (2 H, m, H1), 5.75-5.89 (1 H, m, H2). ¹³C NMR (MeOH-d ₄): δ 8.1 (CH₃, -CH₂ CH₃), 32.6, 38.6 (CH₂, C5, -CH₂CH₃), 44.4 (CH₂, C3), 58.9 (CH₃, OCH₃), 70.0 (CH₂, C6), 74.5 (C, C4), 118.0 (CH₂, C1), 135.4 (CH, C2). EI m/z (%) [M⁺ - 41] 117 (21), 99 (6), 85 (35), 69 (15), 57 (100), 45 (95).
4-Hydroxy-6-methoxy-4-methyl-hept-1-ene (4f)
¹H NMR (MeOH-d ₄): δ 1.12 (3 H, s, CH₃), 1.15 (3 H, d, J = 4.95 Hz, H7), 1.65 (1 H, m), 1.52 (1 H, dd, J = 8.3 Hz, 3.3 Hz), 2.24 (2 H, d, J = 7.4 Hz), 3.30 (3 H, d, J = 1.7 Hz, OCH₃), 3.65 (1 H, m, H6), 5.02 (1 H, m, H1′), 5.06 (1 H, m, H1), 5.84 (1 H, m, H2). ¹³C NMR (MeOH-d ₄): δ 20.2 (CH₃, CH₃), 27.1 (CH₃, C7), 48.1, 48.3 (CH₂, C3, C5), 55.8 (CH₃, OCH₃), 72.9 (C, C4), 75.6 (CH, C6), 118.0 (CH₂, C1), 135.8 (CH, C2).
EI m/z (%) [M⁺ - 41] 117 (31), 85 (19), 69 (14), 59 (91), 43 (100).
4-Hydroxy-6-methoxy-4,5-dimethyl-hept-1-ene (4g)
EI m/z (%) [M⁺ - 41] 99 (2), 83 (2), 71 (1), 56 (94), 43 (100).

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14

Modelling studies were conducted using MacSpartanPro software, version 1.0, Wavefunction, Inc. Irvine USA. Equilibrium geometries were calculated using semi-empirical methods, AM1 model. Conformer distributions were analysed using Molecular Mechanics method of analysis, MMFF model.

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