J. E. D. Martins et al. / Tetrahedron: Asymmetry 14 (2003) 683–688
687
sulfate, filtered and the solvents were evaporated to
4.9. Racemization process of (+)-10
afford ( )-10 (0.54 g, 80%) as a white solid. Mp:
190–192°C (lit.12 190–192°C) 1H NMR (200 MHz,
CDCl3) l (ppm): 4.2 (s, 1H, H10 a-OH). 13C NMR (300
MHz, CDCl3) l (ppm): 36.9 (CH2), 37.0 (CH2), 43.0
(CH), 43.1 (CH), 43.4 (CH), 45.0 (CH), 49.3 (CH), 50.0
(CH), 50.9 (CH), 52.8 (CH), 75.0 (CH), 215.5 (C).
FTIR (CHCl3): w (cm−1): 3410 (OH), 1731 (CꢁO).
Into a 10 cm×1cm (internal diameter) glass ampoule
was added (+)-10 (0.03 g, 0.15 mmol, ee=85%, [h]2D0=
+34.0). The ampoule was closed under vacuum and
heated in an oven for 1 h at 215°C. After cooling, 0.025
g of white crystals were removed from the ampoule.
Analysis of the crystals (specific rotation measurement)
showed the formation of ( )-10.
4.6. (−)-10-exo-Acetoxy-pentacyclo[6.2.1.13,6.02,7.05,9]-
dodeca-4-one, (−)-11 and (+)-10-exo-hydroxy-penta-
cyclo[6.2.1.13,6.02,7.05,9]dodeca-4-one, (+)-10
4.10. Molecular orbital calculations
MO calculations using the 6-31G* ab initio method
were performed using the Spartan Program18 package
on an AMD DURON 800 MHz PC computer with 128
Mb of RAM. The best conformation of the alcohol
(+)-10 was obtained from rotational analysis of the
C(10)−O bond by a change of 30° in the initial point of
calculations.
Lipase (50% w/w of substrate) was added to a solution
of 0.3 g of ( )-10 (1.6 mmol) in vinyl acetate (10 mL),
and the suspension was shaken at 250 rpm at 25°C.
When 46% degree of conversion was achieved (7 h), the
enzyme was filtered and the excess of vinyl acetate was
evaporated. The products were separated by flash
column chromatography (cyclohexane:ethyl acetate
9:1), giving (+)-10 (0.148 g, 0.77 mmol, 46%) [h]2D0=
+30.4 (c 1.0, ethyl acetate) ee=85%, mp 190–192°C.
HRMS: calcd for C12H14O2, 190.24418 [M+]; found:
190.09938 and (−)-11 (0.170 g, 0.73 mmol, 44%), [h]2D0=
−31.0 (c 1.0 ethyl acetate) ee >95%, mp 88–90°C.
HRMS: calcd for C14H16O3, 232.28182 [M+]; found:
232.10903.
Acknowledgements
The authors thank for financial support from Conselho
Nacional de Pesquisa Cient´ıfica e Tecnologica (CNPq),
Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Ensino
Superior (CAPES) and Fundac¸a˜o de Amparo a`
Pesquisa do Estado do Rio Grande do Sul
(FAPERGS). The authors are also indebted to Amano
Enzyme USA co. Ltd. for kindly providing the lipase
AY ‘Amano’ 30 (Candida rugosa). Help from Dr. J.
Spencer (James Black Foundation, England) in proof
reading the manuscript was greatly appreciated.
4.7. (+)-10-exo-Acetoxy-pentacyclo[6.2.1.13,6.02,7.05,9]-
dodeca-4-one, (+)-11
To a stirred solution of (+)-10 (0.1 g, 0.53 mmol) in
CH2Cl2 (15 mL) were added acetic anhydride (0.12
mL), triethylamine (0.12 mL) and catalytic 4-dimethyl-
aminopyridine (DMAP). The solution was stirred for
24 h at rt and then a 5% HCl solution was added and
the crude reaction mixture was stirred for 1 h. The
aqueous layer was extracted with ethyl ether (3×15 mL)
and the ethereal extracts were washed with water (3×20
mL), dried over magnesium sulfate, filtered and the
solvents were evaporated to afford (+)-11 as a white
solid (0.1 g, 82%) ([h]2D0=+26.0, c 1.0, ethyl acetate,
References
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1
ee=85%), mp 88–90°C, H NMR (200 MHz, CDCl3) l
(ppm): 1.9 (s, 3H, CH3), 5.0 (s, 1H, H a-OAc). 13C
NMR (300 MHz, CDCl3) l (ppm): 21.0 (CH3), 36.9
(CH2), 37.5 (CH2), 41.4 (CH), 42.7 (CH), 43.2 (CH),
45.3 (CH), 47.3 (CH), 49.1 (CH), 50.9 (CH), 52.9 (CH),
78.5 (CH), 169.7 (C), 215.2 (C). FTIR (CHCl3): w
(cm−1): 1746 (CꢁO overlapping of the ester and ketone
bands).
1
4.8. Enantiomeric excess analysis by H NMR spectro-
scopy using a chiral chemical shift reagent
A high resolution of the signals has been achieved for
the enantiomeric proton H(10) (a-OAc) of ( )-11.
Sequential addition of the chiral chemical shift reagent
tris [3-(heptafluoropropylhydroxymethylene)-(+)-cam-
phorato] europium(III)9 Eu(hfc)3 (5 mg) to a CDCl3
solution of ( )-11 (10 mg) in a 5 mm NMR tube,
achieved the best result with 25 mg of Eu(hfc)3. The
difference in chemical shift (DDl) of the enantiomeric
hydrogens H(10) (a-Oac) was 0.16 ppm.
6. (a) Costa, V. E. U.; Alifantes, J.; Axt, M.; Mollmann, M.
E. S.; Seidl, P. R. J. Braz. Chem. Soc. 1999, 10, 341; (b)