Facile Synthesis of Cross-Conjugated gem-Disubstituted Trienes via ­Palladium-Catalyzed Cross-Coupling Protocol of 1,1-Disubstituted 2,4-Diiodo-But-1-ene With Alkenes

Abstract

Cross-conjugated coupling products described in the title are obtained in moderate to high yields by the reactions of the corresponding 1,1-disubstituted 2,4-diiodo-but-1-enes, which are derived from the ring-opening reaction of methylenecyclopropanes with iodine, with substituted alkenes in the presence of palladium(II) catalyst under simple Heck-type reaction conditions.

Key words

methylenecyclopropanes - cross-conjugated trienes - cross-coupling reaction - palladium catalyst - alkenes - diiodides

References

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13

Typical Procedure for the Ring-Opening of MCPs 1 by I ₂ in 1,2-Dichloroethane (DCE): Under an ambient atmosphere, MCP 1a (10 mmol), I₂ (10 mmol) and 1,2-dichloroethane (2.5 mL) were added into a Schlenk tube. The mixture was stirred at r.t. for 8 h. The solvent was removed under reduced pressure and the residue was then purified by a flash column chromatography to give product 2a as a yellow solid; mp 112-114 °C. ¹H NMR (300 MHz, CDCl₃) δ = 3.08 (t, J = 7.2 Hz, 2 H), 3.37 (t, J = 7.2 Hz, 2 H), 3.80 (s, 3 H, CH₃O), 3.84 (s, 3 H, CH₃O), 6.84 (d, J = 9.0 Hz, 4 H, Ar), 7.07 (d, J = 6.9 Hz, 2 H, Ar), 7.16 (d, J = 6.9 Hz, 2 H, Ar). ¹³C NMR (75 MHz, CDCl₃): δ = 6.58, 44.53, 55.13, 55.19, 105.46, 113.31, 113.75, 129.91, 130.11, 132.54, 138.99, 149.71, 158.73, 158.79. IR (CH₂Cl₂): 3046, 2954, 2833, 2676, 2299, 2050, 1605, 1508, 1265, 1247, 741, 705 cm^-1. MS: m/z (%) = 520 (84.92) [M⁺], 393 (28.23), 266 (100). HRMS: m/z calcd for C₁₈H₁₈I₂O₂: 519.9396; found: 519.9406.

14

Typical Procedure for the Heck-Type Reaction: Under an ambient atmosphere, 2a (0.25 mmol), 3a (0.30 mmol), Pd(OAc)₂ (0.05 mmol), tetrabutylammonium chloride (TBAC) (0.25 mmol), NaHCO₃ (0.5 mmol) and N,N-dimethylformamide (DMF) (1.0 mL) were added into a Schlenk tube. The reaction mixture was stirred at 100 °C for about 24 h. The reaction solution was washed with saturated brine, dried over anhyd MgSO₄, and then purified by a flash column chromatography to give 5a as a pale yellow solid. Mp: 85-88 °C. ¹H NMR (300 MHz, CDCl₃) δ = 3.72 (s, 3 H), 5.36 (dd, J = 1.2, 11.4 Hz, 1 H), 5.39 (dd, J = 1.2, 17.7 Hz, 1 H), 6.21 (d, J = 15.9 Hz, 1 H), 6.39 (dd, J = 11.4, 17.7 Hz, 1 H), 7.09-7.18 (m, 5 H, Ar), 7.27-7.33 (m, 5 H, Ar), 7.47 (d, J = 15.9 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 51.49, 119.71, 121.65, 127.73, 127.81, 127.89, 128.13, 131.06, 131.11, 132.61, 135.14, 141.10, 141.48, 144.32, 147.80, 167.82. IR (CH₂Cl₂): 3067, 2978, 2304, 115, 1605, 1265, 739 cm^-1. MS m/z (%) = 290 (35.94) [M⁺], 258 (32.98), 215 (100). HRMS: m/z calcd for C₂₀H₁₈O₂: 290.1301; found: 290.1290.

15

To clarify the selectivity of the reaction, an experimental run was carried out on a larger scale of 2d (2.0 mmol) and 3a (2.4 mmol) as the substrates. We found that no other isomer was obtained based on the ¹H NMR spectroscopic data of the reaction mixtures. At present stage, we are not sure of the reason on the selectivity of the reaction of 2c and 3c yet. We have determined the relative configuration of 5g by ¹H NMR as the corresponding coupling constant of the former is 16.5 Hz and 8.7 Hz for the latter (Supporting Information).