Synthesis 2005(19): 3199-3201  
DOI: 10.1055/s-2005-918470
SHORTPAPER
© Georg Thieme Verlag Stuttgart · New York

A Synthesis of (+)-Obtusenyne

S. Y. Frankie Maka, Neil R. Curtisa, Andrew N. Paynea, Miles S. Congrevea, Craig L. Francisa, Jonathan W. Burton*a, Andrew B. Holmes*b
a Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
Fax: +44(1223)336362; e-Mail: jwb1004@cam.ac.uk;
b School of Chemistry, University of Melbourne, Victoria 3010, Australia
Fax: +61(3)83442384; e-Mail: aholmes@unimelb.edu.au;
Further Information

Publication History

Received 15 September 2005
Publication Date:
14 November 2005 (online)

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.

10

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

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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.

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

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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.