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Synlett 2010(4): 517-520  
DOI: 10.1055/s-0029-1219526
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Formal Total Synthesis of (±)-Conduramine E Utilising the Bryce-Smith-Gilbert Photoamination Reaction

David Chappell, Michael G. B. Drew, Shane Gibson, Laurence M. Harwood, Andrew T. Russell*
Department of Chemistry, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK
Fax: +44(118)3786331; e-Mail: a.t.russell@reading.ac.uk;
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Publication History

Received 17 December 2009
Publication Date:
11 February 2010 (online)

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Abstract

Utilising a Bryce-Smith-Gilbert photoamination of benzene as a key step, a synthesis of ()-conduramine E was carried out. A highly regioselective dihydroxylation of a cyclic diene was effected utilising Sharpless AD-mix-b.

Key words

Bryce-Smith-Gilbert photoamination - (±)-condur­amine E - diastereocontrolled synthesis

    References and Notes

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  • 1b

    Synthesis of 1
    A solution of N-tert-butylcyclohexa-2,5-dienylamine contaminated with N-tert-butylcyclohexa-2,4-dienylamine (2.5 g, 16.5 mmol)²b and Et3N (4.65 mL, 33.4 mmol, 2 equiv) in dry Et2O (375 mL) was stirred under argon at 0 ˚C before formic acetic anhydride (1.75 mL, 19.8 mmol, 1.2 equiv) was added slowly, and the resulting yellow solution left stirring for 4 h whilst allowing to warm to r.t. The reaction was quenched with H2O and the layers separated. The aqueous layer was extracted with Et2O (3 × 150 mL), the combined organic extracts dried over MgSO4, and the solvent removed in vacuo. The resultant amber oil was purified via flash column chromatography (Florisil®, gradient; hexane-EtOAc = 19:1 to 2:1) to give N-tert-butyl-N-cyclohexa-2,5-dienylformamide (1) as a colourless crystalline solid (1.83g, ca. 62%); mp 44-47 ˚C; R f = 0.11 (SiO2, hexane-EtOAc = 7:3). IR (thin film): νmax = 3030, 2972, 2814, 1668 (C=O stretch), 1220. ¹H NMR (250 MHz, CDCl3): δ = 1.42 [9 H, s, C(CH3)3, rotamer A], 1.48 [9 H, s, C(CH3)3, rot. B], 2.64-2.69 [2 H, m, H(4), rot. A and B], 4.56-4.63 [1 H, m, H(1), rot. A], 4.80-4.95 [1 H, m, H(1), rot. B], 5.57-5.91 [4 H, m, 2 × CH=CH, rot. A and B], 8.16 [1 H, s, C(O)H, rot. B], 8.51 [1 H, s, C(O)H, rot. A], [rot. A/rot. B = 2:1]. ¹³C NMR (63 MHz, CDCl3): δ = 25.95, 26.39 [CH2, C(4), rots. A and B], 29.33 [CH3, C(CH3)3, rot. B], 29.71 [CH3, C(CH3)3, rot. A], 48.07, 49.02 [CH, C(1), rot. A and B], 56.96, 57.24 [C, C(CH3)3, rot. A and B], 126.28, 126.41, 126.93, 127.86 [CH, C(2,3,5,6), rot. A and B], 162.72 [C, C(O)H, rot. A], 165.89 [C, C(O)H, rot. B]. HRMS (CI): m/z calcd for C11H17NO [M+]: 179.1310; found: 179.1310. Anal. Calcd (%) for (CHN): C, 73.70; H, 9.56; N, 7.81. Found: C, 73.46; H, 9.68; N, 7.67.

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4

Amberlite® IRA-900 Br3 - form, purchased from Fluka.

5

Crystal Data
C11H20BrNO3, M = 294.19, monoclinic, Z = 4, spacegroup P21/a, a = 11.297 (14) Å, b = 9.511 (11) Å, c = 13.553 (14) Å, β = 106.50 (1)˚, U = 1396 (3) ų. 2765 data were collected with MoKα radiation at 150 K using the Oxford Diffraction X-Calibur CCD System. The crystal was positioned at 50 mm from the CCD. 321 frames were measured with a counting time of 10 s. Data analysis was carried out with the CrysAlis program.¹5 The structure was solved using direct methods with the Shelxs97 program.¹6 The nonhydrogen atoms were refined with anisotropic thermal parameters. The hydrogen atoms bonded to carbon were included in geometric positions and given thermal parameters equivalent to 1.2 times those of the atom to which they were attached. An absorption correction was applied using ABSPACK.¹7 The structure was refined on F² using Shelxl97 [2] to R1 = 0.0903, wR2 = 0.1744 for 872 reflections with I > 2σ(I). Details of the structure have been deposited at the Cambridge Crystallographic Data Centre as CCDC 752251.

10

Procedure
AD-mix-β [K3Fe(CN)6 (0.35 g, 1.08 mmol, 3 equiv), K2CO3 (0.16 g, 1.08 mmol, 3 equiv), (DHQD)2PHAL (2.5 mol%) and K2OsO4˙2H2O (2.5 mol%)] were dissolved in t-BuOH-H2O (1:1; 20 mL) and stirred for 5 min before addition of MeSO2NH2 (29 mg, 0.36 mmol, 1 equiv). The solution was cooled to 0 ˚C before addition of (±)-(3aS,7aR)-3-(tert-butyl)-3,3a,7a-trihydrobenzoxazol-2-one (8, 70 mg, 0.36 mmol) in t-BuOH (1 mL). The reaction was left stirring for 5 h between 0 ˚C and -5 ˚C. The reaction was diluted with MeOH and evaporated to dryness in vacuo. The residue was dissolved in CHCl3-MeOH (9:1) and filtered through a plug of Celite® upon silica gel. The filtrate was concentrated in vacuo to give the crude diol which was purified by flash chromatography (SiO2, CHCl3-MeOH = 9:1) to yield (±)-(3aS,6S,7S,7aS)-3-(tert-butyl)-6,7-dihydroxy-3,6,7,3a,7a-pentahydrobenzoxazol-2-one (9) as a colourless oil that solidified on standing (63 mg, 76%); mp 63-65 ˚C; R f = 0.17 (SiO2, CHCl3-MeOH = 19:1). IR (CHCl3): νmax 3441 (OH stretch), 1728 (C=O stretch) cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 1.37 [9 H, s, -C(CH 3)3], 3.10 (1 H, br s, OH), 3.54 (1 H, d, J = 7 Hz, OH), 4.24-4.27 [2 H, m, H(3a,7)], 4.37-4.40 [1 H, m, H(6)], 4.56-4.61 [1 H, m H(7a)], 5.75 [2 H, br s, H(4,5)]. ¹³C NMR (63 MHz, CDCl3): δ = 28.79 [-C(CH3)3], 52.52 [CH, C(3a)], 54.37 [C, C(CH3)3], 64.25 [CH, C(6)], 67.51 [CH, C(7)], 73.47 [CH, C(7a)], 124.87 [CH, C(4)], 131.60 [CH, C(5)], 156.43 (C, C=O). MS (CI): m/z (%) = 228 (37) [MH+]. HRMS: m/z calcd for C11H18NO4: 228.1236; found: 228.1242.

14

The structure of 11 was confirmed by X-ray crystallography.