A Novel 1,3-Central-to-Axial Chirality Induction Approach to Cyclooctadiene Lignans

Abstract

The catalytic asymmetric synthesis of an axially chiral biaryl, potentially useful intermediate in the synthesis of dibenzocyclooctadiene lignans, has been performed. The key step consisted of a diastereoselective Suzuki coupling between a chiral benzylic alcohol and a sterically hindered boronic ester. The 1,3-induction from the benzylic stereocenter to the biaryl axis proceeded with very good diastereoselectivity.

Keywords

axial chirality - Suzuki coupling - chirality induction - cyclooctadiene lignans

References

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(+)-3: [α]_D ²³ +38.8 (c 1.1, CHCl₃); HPLC (Chiracel OD, hexane-EtOH, 95:5, 1.0 mL/min) t _R 7.8 min (minor enantiomer), 9.2 min (major enantiomer).

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Compound (-)-2d: mp 70 °C; [α]_D ²⁴ -21.4 (c 1.0, CHCl₃); HPLC (C₁₈ Symmetry column, H₂O-CH₃CN, 35:65, 1.0 mL/min) t _R 16.6 min (diastereoisomer 1, 4%), 17.9 min (diastereoisomer 2, 96%); HPLC (Chiralpak AD, heptane-i-PrOH, 98:2, 1.0 mL/min) diastereoisomer 2: t _R 10.8 min (enantiomer 1, 5%), 24.5 min (enantiomer 2, 95%), diastereoisomer 1: t _R 11.4 min (enantiomer 1, 95%), 13.0 min (enantiomer 2, 5%). ¹H NMR [300 MHz, (CD₃)₂CO]
δ = 1.15 (d, J = 6.3 Hz, 3 H), 3.23 (s, 3 H), 3.61 (s, 3 H), 3.74 (s, 3 H), 3.89 (s, 3 H), 4.15 (d, J = 12.0 Hz, 1 H), 4.21 (d,
J = 12.0 Hz, 1 H), 4.25 (q, J = 6.5 Hz, 1 H), 4.33 (d, J = 12.3 Hz, 1 H), 4.45 (d, J = 12.3 Hz, 1 H), 4.57 (s, 2 H), 6.04 (s, 1H), 6.06 (s, 1 H), 6.63 (s, 1 H), 6.98 (s, 1 H), 7.12 (s, 1 H), 7.20-7.32 (m, 5 H) (major diastereoisomer). ¹³C NMR [75.5 MHz, (CD₃)₂CO] δ = 23.9, 55.3, 56.2, 60.9, 61.0, 67.7, 70.8, 74.9, 96.7, 102.1, 105.9, 108.7, 111.0, 126.6, 127.7, 127.9, 128.5, 128.9, 133.5, 138.4, 140.7, 142.5, 147.2, 148.6, 151.2, 154.1 (major diastereoisomer). HRMS (ESI): m/z for [(M + Na)⁺] calcd for C₂₈H₃₂NaO₈: 519.1995; found: 519.1982.

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Crystallographic data for 2d have been deposited with the Cambridge Crystallographic Data Center under number CCDC-203288.