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Synlett 2010(4): 672-674  
DOI: 10.1055/s-0029-1219337
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Expedient Route to an Amine Precursor of Halichlorine and Pinnaic Acid from Nitrocyclopent-1-ene

Brett Stevenson, William Lewis, James Dowden*
School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
Fax: +44(115)9513564; e-Mail: james.dowden@nottingham.ac.uk;
Further Information

Publication History

Received 10 November 2009
Publication Date:
19 January 2010 (online)

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Abstract

Diastereoselective addition of n-propanal to nitrocyclopent-1-ene, aldehyde protection, 1,6-conjugate addition, and cross metathesis provides a facile route to key amine precursors of halichlorine and pinnaic acid.

Key words

nitroalkene - organocatalysis - conjugate addition - ­alkene metathesis

8

Cambridge Crystallographic Data Centre deposition numbers: 6a: 753693; 6b: 753694.

9

Schemes reflect the stereochemical orientation in the crystal structures for convenience of the reader. In fact, the opposite absolute stereochemistry is required for 1 and 2.

14

Data for Selected CompoundEthyl ( E )-5-{2-[1-(1,3-dioxan-2-yl)ethyl]-1-nitrocyclo-pentyl}pent-3-enoate (11)
(2E)-Ethyl-2,4-pentadienoate (0.50 g, 4.0 mmol) was added to of 2-[1-(2-nitrocyclopentyl)ethyl]-1,3-dioxane (5a, 0.83 g, 3.6 mmol), Cs2CO3 (1.33 g, 3.6 mmol), TBAI (0.06 g, 5 mol%) in xylene (70 mL) and CHCl3 (10 mL) and stirred at r.t. for 16 h. Water (100 mL) was added and the mixture extracted with EtOAc (3 × 60 mL). The organic layers were washed with brine (100 mL), dried (MgSO4), filtered, and concentrated. The crude material was purified by silica gel chromatography using PE-EtOAc (95:5) as eluent to give the ester 11 as a colourless oil (1.13 g, 88%). IR (CHCl3): ν = 2976, 1729, 1531, 1470, 1428, 1372, 1280, 1155 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 5.72 (1 H, dt, J = 15.4, 6.8 Hz CH=CHCH2CO2Et), 5.50 (1 H, ddd, J = 15.4, 7.6, 6.8 Hz, CH=CHCH2CO2Et), 4.38 (1 H, d, J = 4.0 Hz, CHO2), 4.15 (2 H, q, J = 7.2 Hz, CH 2CH3), 4.14-4.08 [2 H, m, (OCH a Hb)2], 3.79-3.70 [2 H, m, (OCHa H b)2], 3.12 (1 H, dd, J = 14.4, 6.8 Hz, CCH a HbCH=CH), 3.05 (2 H, d, J = 6.8 Hz, CH2CO2Et), 2.52-2.44 (1 H, m, CHCNO2), 2.38 (1 H, dd,
J = 14.4, 7.6 Hz, CCH a H b CH=CH), 2.32-2.65 [1 H, m, CCH aHbCH2)2], 2.10-1.58 [7 H, m, CHCH(CH 2)2CHa H bCNO2,
(OCH2)CH aHb], 1.36-1.31 [1 H, m, (OCH2)CHa H b], 1.27 (3 H, t, J = 7.2 Hz, CH2CH 3), 0.73 (3 H, d, J = 7.2 Hz, CHCH 3) ppm. (100 MHz, CDCl3): δ = 171.6, 128.0, 127.3, 104.3, 99.4, 66.9, 66.8, 60.7, 49.2, 40.0, 38.1, 35.9, 35.1, 26.6, 25.8, 22.2, 14.2, 10.8 ppm. HRMS: m/z calcd for C18H30NO6: 356.2068; found: 356.2062 [M + H]+. Anal. Calcd for C18H29NO6: C, 60.80; H, 8.17; N, 3.94. Found: C, 61.10; H, 8.28; N, 3.69.

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Data for Selected Compound tert -Butyl ( E )-4-{1-amino-2-[1-(1,3-dioxan-2-yl)ethyl]-cyclopentyl}but-2-enoate (14) Methyl (E)-4-{2-[1-(1,3-dioxan-2-yl)ethyl]-1-nitrocyclopentyl}but-2-enoate (12, 0.05 g, 0.14 mmol), Zn dust (0.18 g, 2.71 mmol), and HCl (1 M, 1.30 mL, 1.35 mmol) was stirred in i-PrOH (2 mL) overnight at r.t. 1 M KOH was added to the reaction until pH >11, then extracted with EtOAc (4 × 10 mL). The organic layers were dried (Na2SO4), filtered, and concentrated to yield amine 14 as a clear oil (0.04 g, 80%). IR (CHCl3): ν = 3010, 2976, 1704, 1449, 1392, 1369, 1240, 1154 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.96 [1 H, ddd, J = 15.6, 8.4, 7.2 Hz, CH=CHCO2(CH 3)3], 5.86 [1 H, dt, J = 15.6, 1.2 Hz, CH=CHCO2(CH 3)3], 4.43 (1 H, d, J = 3.6 Hz, CHO2), 4.16-4.11 [2 H, m, (OCH a Hb)2], 3.79-3.72 [2 H, m, (OCHa H b)2], 2.50 (1 H, ddd, J = 13.6, 8.4, 1.2 Hz, CH a HbCH=CH), 2.32 (1 H, ddd, J = 13.6, 7.2, 1.2 Hz, CHa H b CH=CH), 2.13-2.00 [1 H, m, (OCH2)CH aHb], 1.87-1.35 [18 H, m, CHCH(CH 2)3, (OCH2)CHa H b, CO2(CH 3)3], 0.99 (3 H, d, J = 7.2, CHCH 3) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 165.9, 144.9, 125.7, 105.3, 80.1, 67.0, 66.9, 62.0, 47.6, 44.9, 40.3, 37.0, 28.2, 27.8, 25.9, 22.5, 13.5 ppm. HRMS: m/z calcd for C19H34NO4: 340.2482; found: 340.2492 [M + H]+; m/z calcd for C19H34NO4Na: 362.2302; found: 362.2303 [M + Na]+.