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Synlett 2010(4): 509-513  
DOI: 10.1055/s-0029-1219152
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Probing a Biomimetic Approach to Mycaperoxide B: Hydroperoxidation Studies

Eduarda M. P. Silva, Richard J. Pye, Christine Cardin, Laurence M. Harwood*
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AH, UK
Fax: +44(118)3786121; e-Mail: l.m.harwood@reading.ac.uk;
Further Information

Publication History

Received 13 October 2009
Publication Date:
22 December 2009 (online)

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Abstract

Hydroperoxidation studies on a series of alkene substrates demonstrate the introduction of the hydroperoxide functional group into the required position for a biosynthetically inspired synthesis of mycaperoxide B.

Key words

hydroperoxidation - cobalt catalyst - mycaperoxide - ­marine endoperoxide - Michael addition.

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Typical Procedure for Hydroperoxidation Reaction
Into a flask flushed with oxygen were added 9,10-trans-1-[3′-methylhex-3′-en-6′-ol]-2α,5,5,9β-tetramethyldecahydro-
naphthalen-1α-ol (19, 53 mg, 0.16 mmol), bis(5,5-dimethyl-1-morpholino-1,2,4-hexanetrionato)cobalt(II) (4 mg, 0.008 mmol) and 1,2-DCE (2 mL), and the flask was again charged with oxygen. Triethylsilane (0.052 mL, 0.32 mmol) and t-BuOOH (2 drops) were added via a 1.0 mL gas-tight syringe, and the resulting green solution was stirred vigorously under an oxygen atmosphere at r.t. After stirring for 2.5 h, the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica. Elution with hexane-acetone (9:1) gave pure 21 as a colourless oil (20 mg, 30%). IR (thin film): νmax = 3390, 2929, 2869, 1461, 1375, 1051, 1017, 801, 729 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 3.68-3.63 (2 H, m, H-6′), 1.63-1.25 (20 H, m, H 2,3,4,6,7,8,10 and H-1′,2′,4′,5′), 1.15 and 1.14 (3 H, s, 3′-CH3), 0.97 (9 H, t, J = 7.4 Hz, SiCH2CH3), 0.93 and 0.92 (3 H, s, 9-CH3), 0.858 (3 H, d, J = 6.4 Hz, 2-CH3), 0.860 (3 H, s, 5α-CH3), 0.83 (3 H, s, 5β-CH3), 0.67 (6 H, q, J = 7.4 Hz, SiCH2CH3). ¹³C NMR (100 MHz, CDCl3): δ = 84.6 and 84.5 (COOTES), 77.1 (C-1), 63.3 (C-6′), 46.2 (C-10), 43.5 and 43.4 (C-9), 41.8 and 41.7 (C-6), 36.6 and 36.3 (C-2), 33.8 (5α-CH3), 33.3 (C-5), 32.6 (C-1′), 32.55 and 32.46 (C-8), 32.2 and 32.0 (C-4′), 31.5 (C-2′), 27.6 and 27.5 (C-3), 27.21 and 27.17 (C-5′), 22.1 (5β-CH3), 22.0 (3′-CH3), 21.7 (C-4), 18.7 (C-7), 16.6 and 16.43 (2-CH3), 16.36 and 16.2 (9-CH3), 6.8 [Si(CH2CH3)3], 3.9 [Si(CH2CH3)3]. HRMS (CI): m/z calcd for C27H54O4Si [M]+ : 470.3791; found: 470.3800.

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6′α-[2′′-(1α-Hydroxy-9,10- trans -2α,5,5,9β-tetramethyl-decahydronaphthalen-1-yl)ethyl]-6′β-methyl-1′,2′-dioxan-3′β-ol (23a)
Mp (lit.) 49-50 ˚C. IR (thin film): νmax = 3402, 2930, 2863, 1461, 1451, 1372, 1137, 1088, 989 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 5.26 (1 H, q, J = 4.0 Hz, H-3′), 3.04 (1 H, d, J = 4.0 Hz, OH), 2.07-1.17 (20 H, m, H-4′,5′,1′′,2′′ and H-2,3,4,6,7,8,10), 1.15 (3 H, s, 6′-CH3), 0.87 (3 H, d, J = 8.0 Hz, 2-CH3), 0.87 (3 H, s, 5α-CH3), 0.83 (3 H, s, 5β-CH3). ¹³C NMR (100 MHz, CDCl3): δ = 96.4 (C-3′), 80.9 (C-6′), 77.2 (C-1), 46.3 (C-10), 43.4 (C-9), 41.7 (C-6), 36.5 (C-2), 33.8 (5α-CH3), 33.3 (C-5), 32.1 (C-4′), 31.9 (C-5′), 31.4 (C-2′′), 27.8 (C-8 and C-3), 25.4 (C-1′′), 22.1 (6′-CH3), 22.03 (5β-CH3), 21.7 (C-4), 18.7 (C-7), 16.5 (2-CH3), 16.3 (9-CH3). ESI-HRMS: m/z calcd for C21H38O4Na [M + Na]+ : 377.2662; found: 377.2666.

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Crystal Data for 23a
C21H38O4, M = 354.51, centered monoclinic, C2, a = 24.384 (3), b = 7.4398 (12), c = 11.0398 Å, V = 2000.5 (5) ų, Z = 4, D = 1.177 g cm-³, F(000) = 784. 2586. Independent reflections were collected on an Oxford Gemini S Ultra Image Plate System. The structures was solved by direct methods and refined on F2 using SHELXL97. Final R = 0.0487, weighted R = 0.1345. These data can be obtained free of charge from The Cambridge Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif quoting deposition no. CCDC 750510.