A Short Synthesis of (+)-Bakuchiol

Abstract

The concise enantioselective total synthesis of (+)-bakuchiol has been achieved using an asymmetric 1,4-addition to construct its all-carbon chiral quaternary center based on the induction of chirality by the (2′S)-2′-phenyloxazolidinone auxiliary, followed by a one-pot transformation under aldol reaction conditions. The synthesis was completed in four steps from (E)-geranic acid in an overall yield of 53%.

Key words

bakuchiol - asymmetric 1,4-addition reaction - asymmetric aldol reaction - removal of oxazolidinone - decarboxylation - all-carbon quaternary center

• References and Notes

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• 18 Data for Synthetic (+)-Bakuchiol: [α]_D ²⁰ +26.0 (c 0.45, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.25 (d, J = 8.4 Hz, 2 H), 6.77 (d, J = 8.4 Hz, 2 H), 6.25 (d, J = 16.4 Hz, 1 H), 6.10 (d, J = 16.4 Hz, 1 H), 5.88 (dd, J = 10.8, 17.2 Hz, 1 H), 5.10 (quint t, J = 1.6, 7.2 Hz, 1 H), 5.03 (dd, J = 1.6, 10.8 Hz, 1 H), 5.01 (dd, J = 1.6, 17.2 Hz, 1 H), 4.78 (br s, 1 H), 1.95 (dt, J = 7.2, 9.2 Hz, 2 H), 1.67 (d, J = 1.2 Hz, 3 H), 1.58 (d, J = 0.8 Hz, 3 H), 1.49 (m, 2 H), 1.19 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 155.2, 146.5, 136.5, 131.9, 131.5, 127.9, 127.0, 125.4, 115.9, 112.5, 43.1, 41.9, 26.3, 23.9, 23.8, 18.2. HRMS (EI): m/z [M]⁺ calcd for C₁₈H₂₄O: 256.1821; found: 256.1827.