메뉴 건너뛰기
Synlett
Volumn , Issue 3, 2007, Pages 485-487
Synthesis of enantiomerically pure cyclopentene building blocks
Author keywords

Benzyloxymethyl cuprate; Claisen Ireland rearrangement; Cyclopentenes; Enzymes; Spinosyns
Indexed keywords

BENZYL DERIVATIVE; BENZYLOXYMETHYL CUPRIC ACID; CYCLOPENTADIENE DERIVATIVE; CYCLOPENTENE DERIVATIVE; UNCLASSIFIED DRUG;
EID: 33847353774     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-967937     Document Type: Article
Times cited : (31)
References (20)
  • 5
    • 33847364854 scopus 로고    scopus 로고
    • Angew. Chem. 2006, 118, 5137.
    • (2006) Chem , vol.118 , pp. 5137
    • Angew1
  • 12
    • 33847360956 scopus 로고    scopus 로고
    • For the preparation of 7 the following modified procedure was used. A mixture of diol 4 (8.0 g, 80 mmol, Et3N (7.7 mL, 56 mmol, vinyl acetate (11 mL, 0.12 mol) and pancreatin (30 g) in THF (150 mL) was stirred at r.t. until complete consumption of 4 (TLC, The mixture was filtered, the filter pad of the residue washed with EtOAc (3 x 50 mL) and the solvent evaporated under reduced pressure. Purification of the residue by column chromatography (n-pentane-EtOAc, 3:1) afforded acetate 7 as white crystals (8.2 g, 58 mmol, 72, 99% ee, The diacetate 5 was isolated as by-product in 22% yield; [α]D20 -69.0 (c 1.00, CHCl3, Rf, 0.4 (n-pentane-EtOAc, 1:1, IR (KBr, 3387, 2922, 1726, 1359, 1253, 1087, 1020, 968, 910, 880, 841, 794, 606 cm-1. 1H NMR (300 MHz, CDCl3, δ, 1.66 dt, J, 14.7, 3.8 Hz, 1 H, H B-2
    • +].
  • 15
    • 33847357719 scopus 로고    scopus 로고
    • Synthesis of ent-7. Novo sp 435 lipase (2.0 g) was added to a suspension of diacetate 5 (15.0 g, 81.5 mmol) in a buffer (pH 8, 400 mL) and the mixture was stirred for 18 h at r.t. After that, the reaction was filtered and washed with H2O (100 mL) and EtOAc (2 x 200 mL, The aqueous layer was extracted with EtOAc (3 x 200 mL) and the combined organic fractions were dried (Na2SO4, filtered and concentrated under reduced pressure to afford monoacetate ent-7 as white crystals (11.1 g, 78.1 mmol, 96, 99% ee, α]D20 +66 (c 1.00, CHCl 3, IR (film, 3387, 2922, 1726, 1359, 1253, 1087, 1062, 1020, 968, 910, 880, 841, 794, 606 cm-1. 1H NMR (200 MHz, CDCl 3, δ, 1.66 (dt, J, 14.7, 3.8 Hz, 1 H, 2-H B, 2.06 (s, 3 H, 2′-H, 2.85 (quint, J, 7.3 Hz, 1 H, 2-HA, 4.70-4.75 m, 1
    • +].
  • 16
    • 33847348010 scopus 로고    scopus 로고
    • Synthesis of 8. Magnesia turnings (575 mg, 23.6 mmol) were dried in vacuo at r.t. for 12 h. After activation with bromine and HgCl2 a solution of benzyl chloromethyl ether (0.5 mL, 0.55 g, 3.5 mmol) in THF (2 mL) was added, whereupon the reaction started. The reaction mixture was then cooled immediately to -5°C and more benzyl chloromethyl ether (1.5 mL, 1.65 g, 10.5 mmol) was added carefully as a solution in THF (20 mL, After additional stirring for 2.5 h at -5°C the mixture was transferred into a suspension of CuCN (35 mg, 10 mol, in THF (20 mL) at -20°C and stirred for 5 min. Monoacetate 7 (550 mg, 3.90 mmol) was added and the reaction stirred for further 15 min. After addition of sat. NH4Cl (20 mL) and aq NH 3 (20 mL) the aqueous layer was separated and extracted with EtOAc (3 x 70 mL, The combined organic layers were dried (Na2SO4) and the solvent removed under reduced pressure. Purification of the
    • 2: 204.2649; found: 204.2649.
  • 17
    • 33847414973 scopus 로고    scopus 로고
    • Synthesis of 9. DIAD (3.94 g, 19.5 mmol) was added dropwise to a stirred solution of benzyl ether 8 (1.98 g, 9.74 mmol, Ph3P (5.12 g, 19.5 mmol) and AcOH (2.23 mL, 2.34 g, 39.0 mmol) in Et2O (60 mL) at 0°C. After stirring for 30 min at 0°C the reaction was filtered and the filtrate was washed with cold pentane (4 x 100 mL, The combined extracts were washed with sat. NaHCO3 (100 mL) and the aqueous layer was separated and extracted with pentane (2 x 100 mL, The combined extracts were dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by column chromatography (PE-EtOAc, 20:1) gave acetate 9 as a colorless oil (4.56 g, 18.5 mmol, 95, α] D20 -1.10 (c 1.00, CHCl3, Rf, 0.24 (n-pentane-EtOAc, 15:1, UV/Vis (MeOH, λmax (lg ε, 204.5 (3.926, 251.0 (2.324, 257.0 2.304, 263.0
    • 2: 269.11482; found: 269.11473.
  • 18
    • 33847341596 scopus 로고    scopus 로고
    • Synthesis of 10. n-BuLi (2.5 M in hexane, 12.0 mL, 29.9 mmol) was added dropwise to a stirred solution of DIPA (4.33 mL, 3.10 g, 31.0 mmol) in THF (20 mL) at 0°C. After 5 min HMPA (5 mL) was added and the reaction was cooled to -78°C and stirred for further 10 min whereupon a solution of acetate 9 (5.08 g, 20.7 mmol) in THF (35 mL) was added dropwise. The reaction was maintained at -78°C for additional 20 min. A solution of TBSCl (4.07 g, 27.0 mmol) in THF (5 mL) was added and the reaction was stirred at -78°C for 5 min before warming to r.t. Then pentane (150 mL) and aq NaOH (0.1 M, 150 mL) were added. The aqueous layer was separated and extracted with pentane (2 x 150 ml, The combined pentane extracts were washed with aq NaOH (0.1 M, 2 x 100 mL, H2O (100 mL, dried (Na 2SO4) and the solvent evaporated to give the title compound as a yellow oil 7.45 g, 20.7 mmol, quant, which was used without further purificatio
    • +].
  • 19
    • 33847396451 scopus 로고    scopus 로고
    • Synthesis of 11. A solution of crude silyl ketene acetal 10 (7.45 g, 20.7 mmol) in dry xylene (50 mL) was heated in a sealed tube to 180°C for 18 h. After cooling to ambient temperature the solvent was removed under reduced pressure and the residue dissolved in THF (60 mL, Then, aq NaOH (2 M, 60 mL) was added and the reaction stirred vigorously for 2 h. Pentane was then added (100 mL) and the mixture extracted with aq NaOH (2 M, 3 x 150 mL, The combined aqueous layers were acidified to pH 1 with HCl (6 M) and extracted with EtOAc (3 x 200 mL, The combined organic layers were dried over Na 2SO4 and the solvent evaporated under reduced pressure. Purification of the residue by column chromatography (pentane-EtOAc, 6:1, 0.5% AcOH) gave acid 11 as apale yellow oil (4.43 g, 18.0 mmol, 87, α]D20 +76.1 (c 1.00, CHCl 3, Rf, 0.34 n-pentane-EtOAc, 5:1, 6% AcOH
    • 3: 269.11482; found: 269.11487.
  • 20
    • 33847400953 scopus 로고    scopus 로고
    • Synthesis of 2. BCl3 (ca. 1 M in CH2Cl 2, 2.0 mL, 2.0 mmol) was added dropwise to a solution of acid 11 (246 mg, 1.00 mmol) in CH2Cl2 (10 mL) at -40°C. The reaction was allowed to warm to 0°C while being continuously stirred for 2 h. After being stirred for a further 15 min at 0°C sat. NH4Cl (5 mL) was added, the aqueous layer was separated and extracted with CH2Cl2 (3 x 50 mL, The combined organic extracts were dried (Na2SO4, filtered and evaporated under reduced pressure. After purification of the residue by column chromatography (n-pentane-Et2O, 1:1) 2 was obtained as a white solid (124 mg, 890 μmol, 89, α]D20 +51.0 (c 0.30, CH2Cl2, Rf, 0.22 (n-pentane-Et2O, 1:1, IR KBr, 3444, 3052, 2994, 2900, 2854, 1742, 1484
    • 2: 138.0681; found: 138.0681.

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.