A Synthesis of (+)-Obtusenyne

Abstract

A synthesis of the halogenated medium-ring ether natural product (+)-obtusenyne is reported utilizing a Claisen rearrangement and an intramolecular hydrosilation as key steps.

Key words

total synthesis - natural product - medium-ring ether

References

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10

All new compounds exhibited satisfactory spectroscopic and exact mass/elemental analysis data.

11

The enantiomeric excess and absolute configuration of (+)-2 were determined by analysis of the elimination product methyl (4R,2E)-hydroxyhex-2-enoate that was formed in 86% yield by the treatment of (+)-2 with DBU. The enantiomeric excess of the allylic alcohol was determined by ¹H NMR chiral shift reagent [(+)-Eu(hfc)₃] analysis, with the absolute configuration being assigned by comparison of the optical rotation of the allylic alcohol with that of its enantiomer. [12] The enantiomeric excess of (+)-2 was confirmed by Mosher ester analysis of the secondary alcohol formed by the treatment of 3 with TBAF.

14

The relative stereochemistry of the racemic diol (±)-7 was determined by ¹H NMR NOE and coupling constant analysis of the derived acetonide. [9c]

18

NMR data for synthetic 1: ¹H NMR (500 MHz, C₆D₆, 50 °C): δ = 5.92 (dt, 1 H, J = 10.8, 7.3 Hz), 5.53-5.43 (m, 3 H), 4.20-4.13 (m, 1 H), 3.90 (dt, 1 H, J = 10.8, 2.8 Hz), 3.77 (dt, 1 H, J = 10.8, 3.0 Hz), 3.74-3.68 (m, 1 H), 3.02 (ddt, 1 H, J = 14.2, 1.2, 7.1 Hz), 2.92 (d, 1 H, J = 2.0 Hz), 2.87 (dt, 1 H, J = 14.7, 7.0 Hz), 2.78-2.62 (br m, 2 H), 2.52 (ddd, 1 H, J = 12.9, 6.5, 3.0 Hz), 2.40 (ddd, 1 H, J = 13.2, 6.6, 2.9 Hz), 1.91 (dqn, 1 H, J = 14.2, 7.4 Hz), 1.74 (dqn, 1 H, J = 14.2, 7.4 Hz), 0.85 (t, 1 H, J = 7.4 Hz). ¹³C NMR (125 MHz, C₆D₆, 34 °C): δ = 140.7 (C-4), 110.7 (C-3), 82.8 (C-1), 80.1 (C-2), 63.3 (C-7), 56.6 (C-12), 35.3 (C-5), 32.0 (C-8), 31.2 (br, C-11), 28.7 (C-14), 10.1 (C-15). Owing to the conformational mobility of the natural product the signals due to C-6 and C-13 in the ¹³C NMR spectrum were broadened to the baseline. Signals assignable to C-9 and C-10 were obscured by solvent.