Regiospecific substitution of the β-vinylic sp2 carbon of cyclohexenones bearing the α-chloro- and β-tosylate-groups: Single crystal XRD/Hirshfeld surface/in-silico studies of three representative compounds

Abstract

2-Chloro-3-tosyl-5,5-dimethyl-2-cyclohexenone was subjected to a series of regiospecific Suzuki-Miyaura cross-coupling reactions in suspensions of nine different substituted boronic acids, Pd(OAc)₂, P(Ph₃)₃, K₃PO₄ and 1,4-dioxane solvent, under sealed tube conditions. The regiospecific substitution of the tosyl-group by the aryl group in preference over the chloride- group was observed. A comparison between the bromo- and tosylate group’s reactivities is highlighted. Using the methodology, the products: 2-chloro-3-aryl-5,5-dimethyl-2-cyclohexenones were isolated in greater than 85% yields. Good quality crystals of three representative compounds were obtained by slow evaporation technique and subjected to single crystal XRD studies, Hirshfeld surface analysis, 3-D energy framework, and molecular docking studies. Crystal data for compound 3; C₁₅H₁₇ClO₄S: monoclinic, space group P2₁/c (no. 14), a = 8.8687(3) Å, b = 10.5537(4) Å, c = 16.6862(7) Å, β = 89.807(3)°, V = 1561.78(10) ų, Z = 4, T = 290 K, μ(MoKα) = 0.390 mm^-1, Dcalc = 1.398 g/cm³, 13623 reflections measured (6.716° ≤ 2Θ ≤ 54.962°), 3570 unique (R_int = 0.0467, R_sigma = 0.0512) which were used in all calculations. The final R₁ was 0.0452 (I > 2σ(I)) and wR₂ was 0.1019 (all data). Crystal data for compound 5e; C₂₀H₁₈O₂FCl: monoclinic, space group P2₁/c (no. 14), a = 6.4900(5) Å, b = 18.6070(13) Å, c = 14.2146(11) Å, β = 102.324(2)°, V = 1677.0(2) ų, Z = 4, T = 296(2) K, μ(MoKα) = 0.239 mm^-1, Dcalc = 1.309 g/cm³, 25575 reflections measured (6.262° ≤ 2Θ ≤ 52.224°), 3283 unique (R_int = 0.0494, R_sigma = 0.0307) which were used in all calculations. The final R₁ was 0.0875 (I > 2σ(I)) and wR₂ was 0.2056 (all data). Crystal data for compound 5h; C₁₂H₁₃OSCl: triclinic, space group P-1 (no. 2), a = 6.7517(6) Å, b = 8.8376(9) Å, c = 12.6049(12) Å, α = 109.538(3)°, β = 98.597(3)°, γ = 90.417(3)°, V = 699.52(12) ų, Z = 2, T = 290 K, μ(MoKα) = 0.410 mm^-1, Dcalc = 1.376 g/cm³, 28754 reflections measured (6.114° ≤ 2Θ ≤ 59.288°), 3898 unique (R_int = 0.0544, R_sigma = 0.0349) which were used in all calculations. The final R₁ was 0.1101 (I > 2σ(I)) and wR₂ was 0.2481 (all data).