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Synlett 2011(13): 1912-1916  
DOI: 10.1055/s-0030-1260959
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Studies toward the Bicyclic Peroxylactone Core of Plakortolides

Bogdan Barnych, Jean-Michel Vatèle*
Université Lyon 1, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), UMR 5246 CNRS, Equipe SURCOOF, bât. Raulin, 43, Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
e-Mail: vatele@univ-lyon1.fr;
Further Information

Publication History

Received 11 April 2011
Publication Date:
21 July 2011 (online)

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Abstract

En route to the synthesis of plakortolide E and I, we prepared a β-hydroperoxy vinyl epoxide, obtained from (R)-epi­chlorhydrin in 13 steps and 30% yield, via chemoselective methylenation with Nysted reagent in the presence of Ti(Oi-Pr)2Cl2 and regioselective Mukaiyama-Isayama hydroperoxysilylation. Unexpectedly, acid-catalyzed cyclization of this peroxy epoxide occurred exclusively through a 5-exo mode to furnish a 1,2-dioxolane; this is in contrast to the behavior of hydroxy analogues.

Key words

cyclization - endoperoxides - hydroperoxysilylation - plakortolides

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7

In a recent paper on the isolation and structure elucidation of new plakortolides, Yong et al.²j compared the NMR data of newly isolated plakortolides and plakortolide E. They noted inconsistencies between the reported structure of plakortolide E and of its ¹H NMR and ¹³C NMR data.²c They suggested that these data are those of seco-plakortolide E.

25

Procedure for the Chemoselective Methylenation of Compound 14
To a stirred solution of ketone 14 (0.219 g, 0.585 mmol) in dry THF (8 mL) was added Nysted reagent (20% in THF, 3.51 mL, 1.83 mmol), purchased from Aldrich, at 0 ˚C under N2 atmosphere followed by dropwise addition of TiCl2(Oi-Pr)2 (2. 5 equiv), prepared from TiCl4 (1 M in CH2Cl2; 0.73 mL, 0.73 mmol) and Ti(Oi-Pr)4 (0.217 mL, 0.73 mmol). The reaction mixture was then allowed to reach 15 ˚C and stirred for 15 min. The reaction mixture was cooled to 0 ˚C, treated carefully with H2O (1 mL) and extracted with Et2O (5 × 8 mL). The combined organic layers were washed with sat. NaHCO3 solution and brine. The ethereal solution was filtered through a small pad of silica gel to remove metal species, dried (Na2SO4), and concentrated in vacuo. The residue was chromatographed on silica gel (Et2O-PE, 1:5) to furnish 15 (0.153 g, 70%) as a colorless oil; [α]D ²0 -29.2 (c 1, CH2Cl2). ¹H NMR (300 MHz, CDCl3): δ = 1.26 (br, m, 14 H), 1.38 (s, 3 H), 1.60 (m, 2 H), 1.95 (m, 2 H), 2.35 (d, J = 15 Hz, 1 H), 2.41 (d, J = 15 Hz, 1 H), 2.59 (t, J = 8.1 Hz, 2 H), 3.37 (s, 1 H), 3.76 (s, 3 H), 4.79 (s, 1 H), 4.85 (s, 1 H), 7.16-7.29 (m, 5 H). ¹³C NMR (100 MHz, CDCl3): δ = 21.8, 27.6, 29.4-29.7 (6C), 31.6, 36.1, 36.3, 39.0, 52.3, 59.0, 62.2, 112.2, 125.6, 128.3 (2 C), 128.5 (2 C), 143.0, 145.3, 169.0. IR (neat): 1646, 1736, 1757, 2854, 2927, 3026 cm-¹. ESI-HRMS: m/z calcd for C24H36NaO3 [MNa]+: 395.2557; found: 395.2557.

26

No 6-endo product was detected by ¹H NMR of the crude mixture.