Organic Synthes, Vol. 82, p. 120-125 (2005); Coll. Vol. 11, p. 1068-1073 (2009).
付三押一120 ASYMMETRIC ALCOHOLYSIS OF MESO-ANHYDRIDES
MEDIATED BY ALKALOIDS
(Bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid, 3-endo-
benzyloxycarbonyl, (2R ,3S )-)
2H 2Bn quinidine (1.1 eq.)BnOH (3.0 eq.)toluene, -55 °C, 96 hr
育成牛
Submitted by Carsten Bolm,1 Iuliana Atodirei and Ingo Schiffers. Checked by Motomu Kanai and Masakatsu Shibasaki.
1. Procedure
A flame-dried 250-mL single-necked, round-bottomed flask equipped with a magnetic stirring bar and charged with quinidine (7.14 g, 22 mmol) (Note 1) and endo -bicyclo [2.2.1]hept-5-ene-2,3-dicarboxylic anhydride (3.28 g, 20 mmol) (Note 2) is placed under vacuum for 2 h (Note 3). The evacuated flask is flushed with argon, charged with 100 mL of dry toluene (Note 4), equipped with a rubber ptum and the mixture is cooled to -55 °C (Note 5). Benzyl alcohol (6.2 mL, 6.49 g, 60 mmol) (Note 6) is added dropwi via syringe (over a period of 10 min) to the cooled suspension (Note 7), and the reaction mixture is stirred at the indicated temperature for 96 h (Note 8), during which the solid material gradually dissolves. The resulting clear solution is concentrated in vacuo to dryness, and the resulting residue is dissolved in diethyl ether (125 mL). The solution is washed with 2 N HCl (3 30 mL), and the aqueous layer is back-extracted with ether (5 50 mL). The combined organic layers are extracted with a saturated solution of sodium bicarbonate (5 75 mL), and the resulting aqueous pha is washed with diethyl ether (1 100 mL) in order to remove the traces of benzyl alcohol. The aqueous pha is acidified with 8 N HCl, extracted with CH 2Cl 2 (5 100 mL), and the combined organic layers are dried (MgSO 4), filtered and concentrated to provide 4.97-5.20 g (91-95%, 97-98% ee) of the benzyl hemiester as a white solid (Note 9). The enantiomeric excess o
f the half ester was analyzed by chiral HPLC analysis (Note 10). Alternatively, the enantiomeric excess of the benzyl ester 2 could be determined by GC analysis of the corresponding lactone,3 which was obtained by lective
reduction of the ester group with lithium triethylborohydride (LiBEt3H)
followed by acid-catalyzed lactonization (Note 11).4
U of quinine in the ring opening of endo-bicyclo[2.2.1]hept-5-ene-
怎么炖排骨2,3-dicarboxylic anhydride provides 5.13 g (94%) of the corresponding
enantiomeric benzyl hemiester as a white solid (Note 16).
2. Notes
1. Anhydrous quinidine (95%) and quinine (99%) were purchad
from Acros Organics and ud as supplied.
2. Endo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride (97%)
was purchad from Fluka and ud as received.
3. High vacuum is ud in order to remove traces of moisture.《命运交响曲》
4. Toluene (Merck, >99%), distilled from sodium benzophenone
ketyl radical under argon, was stored over 4 Å molecular sieves.
5. An RL 6 CP type cooling machine was ud in order to maintained
the low temperature.
6. Anhydrous benzyl alcohol (99.8%) was purchad from Sigma-
Aldrich and ud as supplied.
7. The mixture is stirred for at least 1 h at the indicated temperature
before the benzyl alcohol addition.
8. The reaction has been studied extensively on a 1-mmol scale, and
the best asymmetric induction was achieved when the reactions were
performed at low temperature. Slightly lower enantiolectivities have been
obrved when the desymmetrizations were carried out at room temperature.
9. The product has the following characteristics: mp 120 °C
(racemate), 88-90 °C (enantiomer); [ ]
rt = +6.6 (c = 1.90, CHCl3); ee = 97-
D
98% (GC-analysis of the lactone: Lipodex E, t1 = 89.3, t2 = 89.8 major); 1H
NMR (400 MHz,CDCl3) 1.33 (d, J = 8.6 Hz, 1H), 1.48 (dt, J = 8.6, 1.8
Hz, 1H), 3.18 (br s, 1H), 3.30 (br s, 1H), 3.31-3.35 (m, 2H), 4.91 (d, J = 12.6
Hz, 1H), 5.09 (d, J = 12.6 Hz, 1H), 6.22 (dd, J = 3.0, 5.7 Hz, 1H), 6.30 (dd,
J = 3.0, 5.7 Hz, 1H), 7.27-7.36 (m, 5H); 13C NMR (100 MHz, CDCl3)
46.1, 46.5, 48.1, 48.2, 48.7, 66.3, 128.0, 128.2, 128.4, 134.3, 135.5, 135.8,
172.2, 178.7; IR (K Br) 3065, 3032, 2979, 1740, 1707, 1172 cm 1; EI-MS
m/z = 272 (M+, 2), 254 (3), 226 (3), 181 (58), 163 (3), 137 (5), 119 (2), 91
(100), 66 (20). Anal. Calcd for C16H16O4 (272.30): C 70.57; H 5.92. Found:
C 70.55; H 6.01.
121
10. Conditions: Daicel CHIRALPAK AS-H, eluent = i PrOH/hexane = 1/1, flow = 0.5 mL/min, detection = 254 nm, retention time = 10 mi (minor isomer using quinidine) and 12 min (major isomer using quinidine).
11. General procedure for the lactone formation. A 25-mL flame-dried Schlenk-flask equipped with a magnetic stirring bar and rubber ptum is purged with argon and charged with (2R,3S)-3-endo-ben
zyloxycarbonyl bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid (80 mg, 0.29 mmol) in THF (2 mL) (Note 12). The reaction mixture is cooled to 0 °C with an ice-bath and 6 eq. of LiBEt3H (2 mL, 1 M solution in THF) (Note 13) are slowly added. After stirring for 1 h at room temperature 2 N HCl (5 mL) is slowly added and the mixture is stirred for additional 2 h. The aqueous pha is extracted with ethyl acetate (3 5 mL), and the combined organic phas are dried over MgSO4 and filtered. Evaporation of the solvent yields the corresponding lactone, which is analyzed by GC (Note 14).
In order to recover the alkaloid, the acidic aqueous pha, obtained after the first extraction, is neutralized with Na2CO3 and extracted with CH2Cl2 (5 100 mL). The combined organic phas are dried over MgSO4 and filtered. Evaporation of the solvent yields the alkaloid almost quantitatively (6.93 g, 21.36 mmol, 97%) (Note 15).
12. THF was distilled from sodium benzophenone ketyl radical under argon.
13. L iBEt3H was purchad from Acros Organics and ud as received.
14. Capillary gas chromatograms were obtained using the following column and temperature program: Lipodex E: 2,6-O-Dipentyl-3-O-butyryl- -CD. Column head pressure: 1.0 bar N2; 100 °C (50 min), heating rate 3.0 °C/min up to 180 °C (60 min). Injector temperature 200 °C, detector temp
erature 250 °C.
15. The spectral properties of the recovered alkaloid were in accordance with the data published in the literature.5
16. The reaction was performed in a 0.1 M solution (with respect to the anhydride) to give (2S,3R)-3-endo-benzyloxycarbonyl-bicyclo [2.2.1] hept-5-ene-2-endo-carboxylic acid with 96% ee (GC-analysis of the lactone: Lipodex E, t1 = 89.3, major, t2 = 89.8); [ ]rt D = 7.4 (c = 1.00, CHCl3).
122
初中生作文题目Safety and Waste Disposal Information
All hazardous materials should be handled and dispod of in
accordance with "P rudent P ractices in the Laboratory"; National Academy
Press; Washington, DC, 1995.第一次洗衣服作文
3. Discussion
The procedure described above is an improved version of previously
reported alkaloid-mediated asymmetric anhydride openings.2,3,6,7 Structurally
diver anhydrides have been converted into their corresponding benzyl
monoesters with very high enantiomeric excess and excellent yields.
(Table 1) Both enantiomers are available by using either quinidine or
quinine as directing additive. An advantage of the prent protocol using
benzyl alcohol as the nucleophile is that the reactions can be performed
using toluene as solvent, avoiding the u of the previously utilized carbon
tetrachloride. A simple aqueous work-up permits the isolation of the
products in analytically pure form. The synthetic ufulness of the method
was demonstrated by the preparation of optically active -amino acids2 and
unsymmetrical norbornane scaffolds as inducers for hydrogen bond
interactions in peptides.8 In the applications, the benzyl hemiesters were
converted into the corresponding N-Cbz-protected -amino acid benzyl
esters by Curtius degradation, which proceeded with neither racemization
nor epimerization. Subquent cleavage of both protecting groups by simple
hydrogenation yielded the corresponding free -amino acids in excellent
yields in a single step. Finally, the method is also highly lective for the
preparation of the corresponding methyl hemiesters, which have been
isolated with up to 99% yield and 99% ee (on a 1 mmol scale). The
ufulness of such products for the synthesis of optically active -amino
acids, 1,2-diamines, and polymeric materials has also already been
demonstrated.9
1.Institut für Organische Chemie der RWTH Aachen, Landoltweg 1, D-52056
Aachen, Germany.
2.Bolm, C.; Schiffers, I.; Atodirei, I.; Hackenberger, C. P. R. Tetrahedron:
Asymmetry2003, 14, 3455.
3.(a) Bolm, C.; Gerlach, A.; Dinter, C. L. Synlett1999, 195. (b) Bolm, C.; Schiffers,
I.; Dinter, C. L.; Gerlach, A. J. Org. Chem.2000, 65, 6984.
4.Jaeschke, G.; Seebach, D. J. Org. Chem.1998, 63, 1190.
123
5.Raheem, I. T.; Goodman, S. N.; Jacobn, E. N. J. Am. Chem. Soc., 2004, 126,
706.
6.(a) Hiratake, J.; Inagaki, M.; Yamamoto, Y.; Oda, J. J. Chem. Soc., Perkin Trans.
11987, 1053. (b) Hiratake, J.; Yamamoto, Y.; Oda, J. J. Chem. Soc., Chem.
Commun.1985, 1717. (c) Aitken, R. A.; Gopal, J. Tetrahedron: Asymmetry1990, 1, 517. (d) Aitken, R. A.; Gopal, J.; Hirst, J. A. J. Chem Soc., Chem. Commun.
1988, 632.
7.For recent reviews, e: (a) Chen, Y.; McDaid, P.; Deng, L. Chem. Rev.2003,
103, 2965. (b) Tian, S.-K.; Chen, Y.; Hang, J.; Tang, L.; McDaid, P.; Deng, L.
Acc. Chem. Res. 2004, 37, 621; (c) Atodirei, I.; Schiffers, I.; Bolm, C. Chem Rev., accepted for publication.
8.Hackenberger, C. P. R.; Schiffers, I.; Runsink, J.; Bolm, C. J. Org. Chem.2004,
69, 739.
9.(a) Bolm, C.; Schiffers, I.; Dinter, C. L.; Defrère, L.; Gerlach, A.; Raabe, G.
工资属于什么费用
Synthesis2001, 1719. (b) Bolm, C.; Dinter, C. L.; Schiffers, I.; Defrère, L. Synlett 2001, 1875. (c) Bolm, C.; Schiffers, I.; Atodirei, I.; Ozcubukcu, S.; Raabe, G.
New J. Chem.2003, 27, 14.
10.cis-1,2-Cyclobutanedicarboxylic anhydride was obtained by refluxing cis-
cyclobutane-1,2-dicarboxylic acid (Fluka, >97%) in trifluoroacetic anhydride (Acros Organics, 99+%) for 16 h.
11.cis-1,2-Cyclopentanedicarboxylic anhydride was prepared in a 3-step synthesis
according to a literature procedure. Padwa, A.; Hornbuckle, S. F.; Fryxell, G. E.;
Stull, P. D. J. Org. Chem.1989, 54, 817.
12.cis-1,2-Cyclohexanedicarboxylic anhydride (99%) was purchad from Acros
Organics and ud as received.
13.Exo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride was prepared according
to a literature procedure. Canonne, P.; Belanger, D.; Lemay, G. J. Org. Chem.
1982, 47, 3953. It is also available from Sigma-Aldrich (95%).
14.Exo-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride was prepared by
Diels-Alder reaction of maleic anhydride and furan. It is also available from different commercial suppliers (Fluka, Sigma-Aldrich, Acros Organics, Lancaster Synthesis).
Appendix
Chemical Abstracts Nomenclature; (Registry Number)
Quinidine: Cinchonan-9-ol, 6'-methoxy-, (9S)-; (56-54-2)
护肤品哪些好endo-Bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride: 4,7-Methanoisobenzofuran-1,3-dione, 3a,4,7,7a-tetrahydro-, (3aR,4S,7R,7aS)-rel-; (129-64-6)
Benzyl alcohol: Benzenemethanol; (100-51-6)
Lithium triethylborohydride: Borate(1-), triethylhydro-, lithium, (T-4)-; (22560-16-3) Quinine: Cinchona
n-9-ol, 6'-methoxy-, (8 ,9R)-; (130-95-0)
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