PDF herunterladen
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;
Weitere Informationen

Publikationsverlauf

Received 3 September 2003
Publikationsdatum:
07. Oktober 2003 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

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

4

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.

10

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.

12

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

13

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.