Simple Synthesis of Conjugated All-(E)-Polyenic Aldehydes, Ketones, and Esters Using Chemoselective Cross-Metathesis and an Iterative Sequence of Reactions: Application to the Synthesis of Navenone B

Abstract

By using a very simple sequence of reactions such as allylation, acetylation, chemoselective cross-metathesis, and elimination, even and odd conjugated all-(E)-polyenes can be synthesized from very simple alkenes.

Key words

polyenes - cross-metathesis - elimination - allylation - navenone B

References and Notes

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17

Synthesis of Compound 4
To a solution of alkene 3 (190 mg, 0.45 mmol) in CH₂Cl₂ (2.3 mL) was added at r.t. ethyl acrylate (0.15 mL, 1.35 mmol) and Ru-II (14 mg, 0.023 mmol). The reaction mixture was stirred at r.t. overnight and then concentrated in vacuo. Purification of the residue by flash chromatography (hexane/EtOAc, 99:1) afforded 4 (154 mg, 69%) as a yellow oil. R _f  = 0.43 (hexane/EtOAc, 9:1). IR: 1739, 1720, 1656, 1232 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.66 (m, 4 H), 7.41 (m, 6 H), 6.83 (dt, J = 15.8, 7.2 Hz, 1 H), 5.85 (dt, J = 15.8, 1.5 Hz, 1 H), 5.76 (m, 1 H), 5.47 (dt, J = 15.5,
6.8 Hz, 1 H), 5.34 (m, 1 H), 4.18 (q, J = 6.8 Hz, 2 H), 3.69 (t, J = 6.4 Hz, 2 H), 2.49 (m, 2 H), 2.28 (q, J = 6.8 Hz, 2 H), 2.02 (s, 3 H), 1.26 (t, J = 6.8 Hz, 3 H), 1.04 (s, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 170.1, 166.2, 143.3, 135.6, 133.8, 131.6, 129.6, 129.1, 127.6, 124.2, 72.8, 63.1, 60.3, 37.3, 35.6, 26.8, 21.2, 19.2, 14.2. MS: m/z = 377, 241, 199, 105.

18

Synthesis of Compound 5
To a solution of nonconjugated dienic ester 4 (147 mg, 0.30 mmol) in THF (1 mL) was added at r.t. DBU (1 mL, 6.7 mmol). The mixture was stirred for 15 min then neutralized with sat. aq NH₄Cl. The layers were separated, and the aqueous phase was extracted with EtOAc. The combined organic layers were dried (MgSO₄), filtered, and concentrated in vacuo. Purification of the residue by flash chromatography (hexane/EtOAc, 95:5) afforded conjugated triene 5 (70 mg, 54%) as a pale yellow oil. R _f  = 0.61 (hexane/EtOAc, 9:1). IR: 1710, 1619, 1257 cm^-¹.^¹H NMR (300 MHz, CDCl₃): δ = 7.66 (m, 4 H), 7.41 (m, 6 H), 7.30 (dd, J = 15.5, 11.5 Hz, 1 H), 6.44 (dd, J = 15.1, 10.2 Hz, 1 H), 6.13 (dd, J = 15.1, 11.5 Hz, 1 H), 6.09 (dd, J = 14.8, 10.2 Hz, 1 H), 5.92 (dt, J = 14.8, 6.4 Hz, 1 H), 5.85 (d, J = 15.5 Hz, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 3.69 (t, J = 6.4 Hz, 2 H), 2.39 (q, J = 6.4 Hz, 2 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.04 (s, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 167.2, 144.7, 140.9, 136.6, 135.6, 133.8, 131.6, 129.6, 128.2, 127.6, 120.3, 63.2, 60.2, 36.3, 26.8, 19.2, 14.3. MS: m/z = 377, 227, 199, 105.