Sulfanyl Radical-Induced Cyclization of Linalyl Acetate to the Iridane Skeleton: A Short Synthesis of (±)-Dehydroiridomyrmecin

Alejandro F. Barrero; Simeón Arseniyadis; M. Mar Herrador; José F. Quílez del Moral; Jesús F. Arteaga; Elena M. Sánchez

doi:10.1055/s-2005-863729

LETTER

Sulfanyl Radical-Induced Cyclization of Linalyl Acetate to the Iridane Skeleton: A Short Synthesis of (±)-Dehydroiridomyrmecin

Alejandro F. Barrero*^a, Simeón Arseniyadis^b, M. Mar Herrador^a, José F. Quílez del Moral^a, Jesús F. Arteaga^a, Elena M. Sánchez^a
^a Department of Organic Chemistry, Institute of Biotechnology, University of Granada, Avda. Fuentenueva, 18071 Granada, Spain
Fax: +34(958)243318; e-Mail: afbarre@goliat.ugr.es;
^b Institute de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette, France

Abstract

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Abstract

Sulfanyl radicals promote radical cyclization both in linalyl acetate (2) and its derivative 3, leading highly selectively to monoterpenoids with an iridane skeleton. We have investigated the addition of different sulfanyl radicals such as PhS^• , 4-NO₂C₆H₄S^• and PhCH₂CH₂S^• and found that the latter radical produces the best results (87-93%). Natural iridoid dehydroiridomyrmecin (1) at an overall yield of 28% was synthesized in four steps using this method.

Key words

sulfanyl radical - iridane skeleton - addition-cyclization reaction - polyprenes - dehydroiridomyrmecin

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References

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Preparation of Dehydroiridomyrmecin ( 1).
Trifluoroacetic anhydride (1.02 mL, 7.32 mmol) was added to a stirred solution of sulfoxide 13 (560 mg, 1.83 mmol) in CH₂Cl₂ (73 mL) at 0 °C. The mixture was stirred for 30 min at 0 °C and then 1 N aq NaOH (18 mL) and THF (60 mL) were added and stirring continued for 4 h at r.t. The reaction mixture was extracted with Et₂O and the combined organic layer was washed with aq NH₄Cl and brine. Evaporation of the solvent followed by column chromatography (petroleum ether-Et₂O, 5:1) furnished 60 mg (11%) of methyl 7-trifluoroacetoxy irid-1-ene-9-oate (14) and 140 mg (46%) of dehydroiridomyrmecin (1).
Compound 14: ¹H NMR (400 MHz, CDCl₃): δ = 1.12 (3 H, d, J = 7.0 Hz), 1.74 (3 H, s), 1.74-1.82 (1 H, m), 1.97-2.05 (1 H, m), 2.15-2.35 (2 H, m), 2.75 (1 H, dq, J = 3.9, 7.0 Hz), 3.03 (1 H, br s), 3.56 (3 H, s), 4.88 (1 H, d, J = 12.2 Hz), 4.97 (1 H, d, J = 12.2 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 14.3, 14.4, 24.6, 37.3, 41.2, 50.1, 51.5, 63.4, 124.6, 128.4, 144.9, 175.6 (2 C). IR (film): 2952, 1783, 1734, 1457, 1348, 1220, 1164 cm^- ¹.
Dehydroiridomyrmecin ( 1): ¹H NMR [400 MHz, (CD₃)₂CO]: δ = 1.01 (3 H, d, J = 7.2 Hz), 1.40-1.51 (1 H, m), 1.70 (3 H, s), 1.85-1.97 (1 H, m), 2.20-2.30 (1 H, m), 2.35-2.45 (1 H, m), 2.90 (1 H, quint., J = 7.2 Hz), 3.15-3.25 (1 H, m), 4.77 (1 H, d, J = 13.1 Hz), 4.87 (1 H, d, J = 13.1, Hz). ¹³C NMR [100 MHz, (CD₃)₂CO]: δ = 11.6, 13.6, 27.1, 38.3, 40.3, 46.9, 65.8, 130.0, 137.0, 174.9. IR (film): 2948, 1733, 1437, 1376, 1206, 1156 cm^- ¹. HRMS (CI): m/z calcd for C₁₀H₁₅O₂ [M + H]⁺: 167.1072; found: 167.1070.