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Synlett 2003(14): 2252-2254  
DOI: 10.1055/s-2003-42061
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Stereoselective 1,4-Addition of the Enolate Generated from 6-Deoxy-d-Glucopyranoside-Derived Propionyl Ester to Methyl Crotonate: Application to Total Synthesis of (-)-Lasiol

Shingo Asano, Tetsuo Tamai, Kiichiro Totani, Ken-ichi Takao, Kin-ichi Tadano*
Department of Applied Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Fax: +81(45)5661571; e-Mail: tadano@applc.keio.ac.jp;
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Publication History

Received 3 September 2003
Publication Date:
07 October 2003 (online)

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Abstract

1,4-Addition of the enolate generated from methyl 6-deoxy-2,3-di-O-(t-butyldimethylsilyl)-4-O-propionyl-α-d-gluco-pyranoside to methyl crotonate provided a single anti-adduct with exceptionally high stereoselectivity. From this adduct, (-)-lasiol, an acyclic monoterpene alcohol isolated from the males of Lasius meridionalis ants, was synthesized concisely.

Key words

asymmetric synthesis - 1,4-addition - d-glucose - chiral auxiliary - (-)-lasiol

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Synthesis of Methyl 6-deoxy-4-O-[(2S,3S)-4-methoxy-carbonyl-2,3-dimethylbutanoyl]-2,3-di-O-tert-butyl-dimethylsilyl-α-d-glucopyranoside (4). The following reaction was carried out under Ar. To a cooled (-78 °C) stirred solution of 2 (1.05 g, 2.27 mmol) in THF (21 mL) was added NaHMDS (1.0 M solution in THF, 3.40 mL, 3.40 mmol). The solution was stirred at -78 °C for 30 min and then methyl crotonate (0.359 mL, 3.40 mmol) was added. After being stirred at -78 °C for 30 min and at 0 °C for 1.5 h, the reaction mixture was quenched with sat. aq NH4Cl (2 mL). This was diluted with EtOAc (60 mL) and washed with sat. aq NH4Cl (30 mL × 3). The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc-hexane = 1:40-1:20) to provide 965 mg (75%) of 4 (anti/syn = >95:5, dr of anti = >95:5 based on 1H NMR analysis) as a colorless oil and 153 mg (15%) of 2 was recovered. Compound 4: TLC, Rf 0.52 (EtOAc-hexane = 1:5). IR (neat): 2930, 1740, 1470, 1385, 1360, 1250 cm-1. 1H NMR (270 MHz): δ = 0.03, 0.09, 0.10, 0.11 (each s, each 3 H), 0.83, 0.92 (each s, each 9 H),1.02 (d, J = 7.0 Hz, 3 H), 1.07 (d, J = 7.0 Hz, 3 H),1.14 (d, J = 6.3 Hz, 3 H), 2.15 (dd, J = 9.9, 15.9 Hz, 1 H), 2.36-2.46 (m, 1 H), 2.40 (dd, J = 3.8, 15.9 Hz, 1 H), 2.56 (dq, J = 3.0, 7.0 Hz, 1 H), 3.37 (s, 3 H), 3.65 (dd, J = 3.5, 9.1 Hz, 1 H), 3.67 (s, 3 H), 3.74 (dq, J = 6.3, 9.6 Hz, 1 H), 3.90 (t, J = 9.1 Hz, 1 H), 4.61 (d, J = 3.5 Hz, 1 H), 4.68 (dd, J = 9.1, 9.6 Hz, 1 H). 13C NMR (75 MHz): δ = 2 × -4.48, -3.34, -2.90, 11.50, 17.65, 17.81, 17.91, 18.41, 3 × 25.86, 3 × 26.15, 32.73, 37.29, 43.82, 51.57, 54.99, 65.40, 71.80, 74.40, 76.79, 100.01, 173.13, 174.25. HRMS: m/z [M+ - t-Bu] calcd for C23H45O8Si2: 505.2653, found: 505.2656.

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Synthesis of (-)-Lasiol (3). The following reaction was carried out under Ar. To a cooled (-78 °C) stirred solution of 4 (681 mg, 1.21 mmol) in CH2Cl2 (13.5 mL) was added DIBAL-H (1.01 M solution in toluene, 1.44 mL, 1.45 mmol). The resulting solution was stirred at -78 °C for 1 h and then quenched with H2O (5 mL). The resulting precipitates were removed by filtration through a Celite-pad and washed well with EtOAc. The combined filtrate and washings were concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc-toluene = 1:60) to provide 556 mg (86%) of 5 as a colorless oil. Compound 5: TLC, Rf 0.46 (EtOAc-hexane = 1:3). IR (neat): 2935, 1740, 1475, 1360, 1250 cm-1. 1H NMR (270 MHz): δ = 0.03, 0.09, 0.10, 0.10 (each s, each 3 H), 0.83, 0.92 (each s, each 9 H), 1.03 (d, J = 6.5 Hz, 3 H), 1.08 (d,
J = 6.5 Hz, 3 H), 1.08 (d, J = 6.5 Hz, 3 H), 2.32 (ddd, J = 1.8, 10.3, 17.6 Hz, 1 H), 2.51-2.57 (m, 3 H), 3.37 (s, 3 H), 3.65 (dd, J = 3.4, 9.4 Hz, 1 H), 3.72 (dq, J = 6.5, 9.4 Hz, 1 H), 3.90 (t, J = 9.4 Hz, 1 H), 4.60 (d, J = 3.4 Hz, 1 H), 4.68 (t, J = 9.4 Hz, 1 H), 9.76 (d, J = 1.8 Hz, 1 H). 13C NMR (75 MHz): δ = -4.46, -4.41, -3.32, -2.91, 11.33, 17.81, 17.93, 18.11, 18.41, 3 × 25.86, 3 × 26.14, 29.89, 43.92, 46.77, 55.02, 65.30, 71.79, 74.38, 76.80, 100.03, 174.25, 201.24. HRMS: m/z [M+ - t-Bu] calcd for C22H43O7Si2: 475.2547, found: 475.2549.
The following reaction was carried out under Ar. To a cooled (0 °C) stirred solution of (isopropyl)triphenylphosphonium iodide (1.31 g, 3.03 mmol) in THF (20 mL) was added n-BuLi (2.66 M solution in hexane, 1.14 mL, 3.03 mmol). The solution was stirred at 0 °C for 4 min. The resulting deep red solution was cooled to -78 °C for 15 min, then a solution of 5 (534 mg, 1.01 mmol) in THF (10 mL) was added dropwise. After being stirred at -78 °C for 30 min then at 0 °C for 1 h, the reaction mixture was quenched with sat. aq NH4Cl (2 mL). The mixture was diluted with EtOAc (28 mL) and washed with sat. aq NH4Cl (14 mL × 3). The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc-hexane = 1:60) to provide 432 mg (76%) of 6 as a colorless oil. Compound 6: TLC, Rf 0.83 (EtOAc-hexane = 1:5). IR (neat): 2930, 1740, 1475, 1360, 1250 cm-1. 1H NMR (270 MHz): δ = 0.05, 0.09, 0.10, 0.11 (each s, each 3 H), 0.84, 0.92 (each s, each 9 H), 0.92-0.95 (m, 3 H), 1.08 (d, J = 7.0 Hz, 3 H), 1.14 (d, J = 6.2 Hz, 3 H), 1.58, 1.69 (each s, each 3 H), 1.79-2.02 (m, 3 H), 2.53 (dq, J = 2.9, 7.0 Hz, 1 H), 3.37 (s, 3 H), 3.66 (dd, J = 3.4, 9.0 Hz, 1 H), 3.72 (dq,
J = 6.2, 9.8 Hz, 1 H), 3.91 (t, J = 9.0 Hz, 1 H), 4.61 (d, J = 3.4 Hz, 1 H), 4.69 (dd, J = 9.0, 9.8 Hz, 1 H), 5.02-5.06 (m, 1 H). 13C NMR (75 MHz): δ = 2 × -4.49, -3.36, -2.91, 11.97, 17.22, 17.80, 17.86, 18.06, 18.37, 25.79, 3 × 25.87, 3 × 26.14, 31.15, 36.71, 44.07, 54.91, 65.55, 71.85, 74.38, 76.49, 100.00, 122.73, 132.62, 174.76. HRMS: m/z
[M+ - t-Bu] calcd for C25H49O6Si2: 501.3068, found: 501.3065. The following reaction was carried out under Ar. To a cooled (-78 °C) stirred solution of 6 (950 mg, 1.70 mmol) in CH2Cl2 (20 mL) was added DIBAL-H (1.01 M solution in toluene, 8.41 mL, 8.50 mmol). The solution was stirred at -78 °C for 15 min, then quenched with H2O (5 mL). The resulting precipitates were removed by filtration through a Celite-pad and washed well with EtOAc. The combined filtrate and washings were concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc-hexane = 1:15) to provide 244 mg (92%) of (-)-lasiol (3) (anti/syn = >95:5 based on 1H NMR analysis, >95% ee based on the corresponding (R)- and (S)-MTPA esters) as a colorless oil, and 642 mg (93%) of 1 was recovered. (-)-Lasiol (3): TLC, Rf 0.32 (EtOAc-hexane = 1:5); [α]D 23 -12.1 (c 0.995, n-hexane) {lit. (-)-lasiol [α]D 22
-12.9 (c 1.02, n-hexane)}. IR (neat): 3340 (br), 2920, 1455, 1375 cm-1. 1H NMR (270 MHz): δ = 0.87 (d, J = 7.0 Hz, 3 H), 0.93 (d, J = 7.0 Hz, 3 H), 1.47-1.68 (m, 2 H), 1.60, 1.70 (each s, each 3 H), 1.74-1.86 (m, 1 H), 1.99-2.08 (m, 1 H), 3.46 (dd, J = 7.0, 10.6 Hz, 1 H). 3.64 (dd, J = 5.1, 10.6 Hz,
1 H), 5.09-5.15 (m, 1 H). 13C NMR (75 MHz): δ = 13.78, 16.97, 17.80, 25.81, 31.40, 35.51, 40.25, 66.11, 123.55, 132.04. HRMS: m/z [M+] calcd for C10H20O: 156.1514, found: 156.1508.

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Kuwahara and Mori also confirmed the enantiomeric purities of their (+) and (-)-lasiols using the Mosher’s ester method, see refs. 6,7.

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We also conducted chrial HPLC analysis of racemic lasiol prepared separately. Unfortunately, we could not find reliable HPLC conditions for complete separation of the enantiomers.