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Synlett 2011(17): 2537-2540  
DOI: 10.1055/s-0030-1260326
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Enantiospecific Approach to Irregular Ligusticum grayi Sesquiterpenes: Synthesis of cis-Preisothapsa-2,8(12)-diene

A. Srikrishna*, K. Mahesh
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Fax: +91(80)3600683; e-Mail: askiisc@gmail.com;
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Publication History

Received 11 July 2011
Publication Date:
22 September 2011 (online)

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Abstract

Enantiospecific syntheses of 1-epi- (or cis-)-preisothapsa-2,8(12)-diene and 1-epi- and 1,8-diepipreisothapsa-2-en-12-ols, starting from the readily available monoterpene (R)-carvone, have been accomplished.

Key words

thapsanes - preisothapsane - enantiospecific synthesis - irregular sesquiterpenes - carvone

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7

Yields refer to isolated and chromatographically pure compounds. All the compounds exhibited spectral data [IR, HRMS, ¹H (400 MHz) and ¹³C NMR (100 MHz) in 1:1 mixture of CDCl3 and CCl4] consistent with their structures.
Selected Spectral Data for (1 R ,2 S ,4 S ,6 S ,9 R )-4-Iso-propenyl-1,7,7-trimethyltricyclo[4.3.0.0 ²,9 ]nonan-8-one (26)
[α]D ²² -139.6 (c 1.4, CHCl3). IR (neat): νmax = 1721, 1376, 1199, 1154, 1091, 1012, 922, 887, 854 cm-¹. ¹H NMR: δ = 4.61 (1 H, s) and 4.54 (1 H, s, C=CH 2), 2.08 (1 H, d, J = 8.9 Hz), 2.10-1.90 (3 H, m), 1.86 (1 H, d, J = 9.6 Hz), 1.67 (3 H, s, olefinic CH3), 1.51 (1 H, q, J = 8.6 Hz), 1.29 (1 H, dd, J = 14.3, 9.2 Hz), 1.35 (3 H, s), 1.09 (3 H, s, tert-CH3), 0.78 (3 H, s, tert-CH3), 0.52 (1 H, td J = 13.8, 7.3 Hz). ¹³C NMR:
δ = 218.8 (C=O), 149.2 (C=CH), 108.5 (CH=C), 53.4 (C, C-7), 45.8 (CH), 38.3 (CH), 38.2 (CH), 31.6 (CH), 28.0 (CH3), 27.6 (C, C-1), 25.4 (CH2), 24.0 (CH2), 22.0 (CH3), 21.4 (CH3), 18.4 (CH3). HRMS: m/z calcd for C15H22O [M + H]: 219.1749; found: 219.1746.
(1 S ,6 R )-6,9,9-Trimethylbicyclo[4.3.0]non-4-en-3,8-dione (30)
[α]D ²³ -201.4 (c 1.6, CHCl3). IR (neat): νmax = 1737, 1681, 1388, 1244, 1120, 787 cm-¹. ¹H NMR: δ = 6.61 (1 H, d, J = 10.2 Hz, H-4), 5.92 (1 H, d, J = 10.2 Hz, H-5), 2.74 (1 H, dd, J = 17.9, 6.9 Hz), 2.57 (1 H, d, J = 18.8 Hz), 2.50 (1 H, d, J = 17.9 Hz), 2.39 (1 H, d, J = 18.8 Hz), 2.45-2.25 (1 H, m), 1.42 (3 H, s), 1.05 (3 H, s, tert-CH3), 0.88 (3 H, s, tert-CH3). ¹³C NMR: δ = 218.8 (C, C-8), 196.3 (C, C-3), 155.4 (CH, C-5), 128.6 (CH, C-4), 52.0 (CH), 50.4 (CH2), 49.3 (C), 37.6 (C), 33.9 (CH2), 28.0 (CH3), 25.9 (CH3), 20.8 (CH3). HRMS: m/z calcd for C12H16O2 [M + Na]: 215.1048; found: 215.1045.
(1 S ,2 S ,6 S )-2,6,9,9-Tetramethylbicyclo[4.3.0]nonan-spiro[8.2′]-1,3-dioxalan-3-one (33)
[α]D ²5 +47.5 (c 2.7, CHCl3). IR (neat): νmax = 1718, 1307, 1255, 1170, 1160, 1081, 1060, 1018, 1090, 951, 850 cm-¹. ¹H NMR: δ = 4.00-3.80 (4 H, m, OCH 2CH 2O), 2.70-2.50 (1 H, m), 2.45-2.05 (3 H, m), 1.78 (1 H, d, J = 13.2 Hz), 1.69 (1 H, dd, J = 13.4, 6.4 Hz), 1.57 (1 H, d, J = 13.2 Hz), 1.38 (1 H, d, J = 10.6 Hz), 1.05 (3 H, d, J = 8.7 Hz, CH3), 1.06
(3 H, s), 1.00 (3 H, s, tert-CH3), 0.95 (3 H, s, tert-CH3). ¹³C NMR: δ = 215.0 (C, C=O), 118.2 (C, C-8), 65.2 (CH2, OCH2CH2O), 64.3 (CH2, OCH2CH2O), 60.1 (CH, C-2), 48.3 (C), 46.7 (CH2, C-7), 42.9 (CH, C-1), 35.9 (C), 35.7 (CH2), 35.1 (CH2), 28.9 (CH3), 23.1 (CH3), 20.4 (CH3), 14.1 (CH3). HRMS: m/z calcd for C15H24O3Na [M + Na]: 275.1623; found: 275.1624.
(1 R ,6 S )-2,3,6,9,9-Pentamethylbicyclo[4.3.0]nonan-2-en-8-one (35)
[α]D ²¹ -62.3 (c 2.4, CHCl3). IR (neat): νmax = 1739, 1378, 1178, 1076 cm-¹. ¹H NMR: δ = 2.34 (1 H, d J = 17.0 Hz), 2.09 (1 H, d J = 17.0 Hz), 2.05 (1 H, br s), 1.89 (1 H, dd J = 16.9, 5.7 Hz), 1.69 (3 H, s, olefinic CH3), 1.66 (3 H, s, olefinic CH3), 1.40-1.20 (3 H, m), 1.21 (3 H, s), 1.07 (3 H, s, tert-CH3), 0.90 (3 H, s, tert-CH3). ¹³C NMR: δ = 222.8 (C, C=O), 126.2 (C, C-2), 123.5 (C, C-3), 59.6 (CH, C-1), 52.9 (CH2), 48.2 (C, C-9), 35.4 (C, C-6), 31.0 (CH2), 30.5 (CH3), 28.8 (CH2), 25.1 (CH3), 21.9 (CH3), 19.9 (CH3), 18.9 (CH3). HRMS: m/z calcd for C14H22ONa [M + Na]: 229.1568; found: 229.1566.
(1 R ,6 S )-2,3,6,9,9-Pentamethyl-8-methylenebicyclo-[4.3.0]non-2-ene [ cis -preisothapsa-2,8 (12)-diene (19)]
[α]D ²¹ +2.8 (c 2.8, CHCl3). IR (neat): νmax = 1654, 1458, 1374, 879 cm-¹. ¹H NMR: δ = 4.78 (1 H, s), 4.74 (1 H, s, C=CH2), 2.37 (1 H, d, J = 14.8 Hz), 2.05 (1 H, d, J = 14.8 Hz), 2.00-1.70 (3 H, m), 1.67 (3 H, s, olefinic CH3), 1.64 (3 H, s, olefinic CH3), 1.48 (1 H, td, J = 12.7, 6.2 Hz), 1.08-1.04 (1 H, m), 1.23 (3 H, s), 0.93 (6 H, s, tert-CH3). ¹³C NMR: δ = 162.8 (C, C-8), 125.5 (C), 124.6 (C), 104.2 (CH2), 62.6 (CH, C-1), 48.8 (CH2, C-7), 44.3 (C), 38.7 (C), 35.0 (CH3), 29.5 (CH2), 29.1 (CH2), 26.2 (CH3), 24.9 (CH3), 20.2 (CH3), 18.9 (CH3).

9

No attempt was made to confirm the stereochemistry of the secondary methyl group in 33 as the carbon would become a sp² centre subsequently.

10

Formation of a single isomer by employing bulky hydroborating agent assisted in assigning the stereochemistry of the alcohols 36a and 36b. Quite expectedly, the ¹H and ¹³C NMR spectra in C6D6 reported² for the natural preisothaps-2-en-12-ol(11), which was assigned to have the trans ring junction, did not match with signals due to either isomer of the mixture of the alcohols 36a,b recorded in C6D6. IR (neat): νmax = 3350, 2954, 2925, 2868, 1596, 1462, 1370, 1020, 1000 cm-¹. ¹H NMR (400 MHz, C6D6): δ [signals due to 1-epipreisothaps-2-en-12-ol (36a)] = 3.60 (1 H, dd, J = 10.3, 7.0 Hz), 3.42 (1 H, dd, J = 10.2, 7.0 Hz), 2.20-1.80 (4 H, m), 1.80 (1 H, br s), 1.74 (3 H, s, olefinic CH3), 1.71 (3 H, s, olefinic CH3), 1.57 (1 H, dd, J = 12.1, 6.2 Hz), 1.40-1.43 (3 H, m), 1.15 (3 H, s), 1.09 (3 H, s, tert-CH3), 1.03 (3 H, s, tert-CH3); δ [signals due to 1,12-diepipreisothaps-2-en-12-ol (36b)] = 3.63 (1 H, dd, J = 10.4, 5.4 Hz), 3.35 (1 H, dd J = 10.4, 8.2 Hz), 2.20-1.80 (4 H, m), 1.76 (3 H, s, olefinic CH3), 1.74 (3 H, s, olefinic CH3), 1.70-1.50 (1 H, m), 1.50-1.20 (4 H, m), 1.29 (3 H, s), 1.09 (3 H, s, tert-CH3), 0.72 (3 H, s, tert-CH3). ¹³C NMR (100 MHz, C6D6): δ [signals due to 1-epipreisothaps-2-en-12-ol (36a)] = 125.6 (C), 124.9 (C), 64.0 (CH2), 63.7 (CH3), 50.5 (CH), 43.8 (CH2), 41.8 (C), 39.2 (C), 30.0 (CH2), 29.4 (CH2), 28.2 (CH3), 27.9 (CH3), 25.7 (CH3), 19.9 (CH3), 17.9 (CH3); δ [signals due to 1,12-diepipreisothaps-2-en-12-ol (36b)] = 125.8 (C), 64.6 (CH), 63.7 (CH2), 50. 6 (CH), 44.6 (C), 43.3 (CH2), 38.0 (C), 36.5 (CH2), 31.4 (CH3), 30.3 (CH3), 29.4 (CH2), 19.9 (CH3), 19.6 (CH3), 17.9 (CH3). The signal due to one of the olefinic carbons is merged in the solvent signals. Spectrum recorded in CDCl3 exhibited the two olefinic carbon resonances at δ = 128.3 and 125.5 ppm. MS: m/z (%) = 222 (10) [M+], 123 (100), 107 (90), 91 (45).