Synthesis, resolution and racemization study of helically twisted o-terphenyls

Abstract

The synthesis, resolution and racemization studies of helical o-terphenyls, useful chiral building blocks are reported.

References

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8. The mixture of racemic 4(2.96 g, 7.46 mmol) and brucine (3.30 g, 8.38 mmol) in 380 ml of absolute ethanol was heated to reflux until TLC showed no more anhydride. The reaction solution was then cooled to room temperature. On standing overnight, a crop of yellow crystals separated, which was filtered off, washed with ethanol and dried under vacuum to give 2.20 g of 4·brucine salt: [α]²²_D=+640. Recrystallization twice of the first crop from CH₂Cl₂–EtOH raised the optical rotation to +665, which on decomposition with HCl afforded the corresponding acid esters: 1.08 g, [α]²²_D+ 1406 (c= 0.098, CHCl₃); ν_max(KBr)/cm^–1 1728, 1697(C=O); δ_H(400 MHz, CDCl₃) 1.43 (t, 3H), 2.66 (m, 1H), 2.81 (m, 5H), 3.01 (m, 1H), 3.19 (m, 1H), 4.44 (q, 2H), 6.69 (d, 1H), 6.90 (t, 1H), 7.21 (t, 1H), 7.30 (d, 1H), 7.33 (t, 1H), 7.47 (d, 1H), 7.59 (d, 1H); δ_C(50 MHz, CDCl₃) 169.4 and 169.2 (C=O, ester), 174.7 and 174.4 (C=O, acid). The mother liquor of the first crop was left open to air at room temperature for several days and the second crop precipitated out. The yellow solid was then filtered off, washed with ethanol and dried under vacuum to give 1.18 g of 4·brucine salt ([α]²²_D– 739), which upon treatment with HCl produced the acid ester: [α]²²_D– 1243 (c 0.093, CHCl₃); ν_max(KBr)/cm ^–1 1727, 1698 (C=O). Heating the acid ester ([α]²²_D– 1243, e.g., 150 mg) at 50 °C under vacuum (5 mmHg) for 6 h, followed by recrystallization once from hexane–CH₂Cl₂ afforded optically pure (M)-4:[α]²²_D– 1518 (c 0.050, CHCl₃).
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12. Single crystals of racemic 4 suitable for X-ray analysis were obtained on slow evaporation of a CH₂Cl₂ solution. Crystal data for 4: C₂₄H₁₅NO₅, M= 397.38, triclinic, space group P1̄, µ= 0.10 mm^-1. a= 8.1376(6), b= 11.0822(8), c= 11.2149(8)Å, α= 103.642(8), β= 98.747(7), γ= 108.001(8)°, V= 906.64(11)ų, T=–100 °C, Z= 2, measured reflections = 5254, unique reflections = 4159, R(int)= 0.016. CCDC 182/1271.
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