K. J. Finn et al. / Tetrahedron 62 (2006) 7471–7476
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provide a crude white solid. The solid was purified by flash
column chromatography (4:1 chloroform/methanol) to give
conduritol E as a white crystalline solid (78 mg, 81%). Mp
194–195 ꢁC (lit.23b mp 193 ꢁC); [a]D20 ꢀ285 (c 1.0, H2O),
lit.23b: [a]D20 ꢀ294 (c 1.0, H2O); Rf 0.18 (chloroform/
3.2.3.7.
(1R,2S)-2-[(Hexyldimethylsilyl)oxy]cyclo-
hexan-1-ol (38). A flask containing a magnetic stirring bar
was charged with dibromide 37 (0.219 g, 0.53 mmol,
1 equiv), triethylamine (0.5 mL, 3.56 mmol, 7 equiv), plati-
num oxide (Adam’s catalyst, 24 mg, 0.11 mmol, 0.2 equiv),
and 0.5 mL MeOH. The reaction flask was evacuated,
flushed with hydrogen via a balloon (1 atm), and stirred until
total consumption of starting material as was observed by
TLC control (6 h). The crude mixture was filtered through
a short plug of Celite, and the solvent was removed under
reduced pressure. The crude residue was purified by flash
column chromatography (pentane/Et2O, 10:1) to give the
title compound as a clear and colorless oil (71 mg, 52%)
with spectral data matching that of previously reported
compound 38. [a]D23 +3.4 (c 1.0, CHCl3), lit.16: [a]D23 +3.3
(c 1.0, CHCl3).
methanol, 4:1); IR (film) n 3434, 1634 cmꢀ1 1H NMR
;
(300 MHz, MeOD) d 5.79 (d, J¼2.1 Hz, 2H), 4.27 (s, 2H),
3.93 (d, J¼0.9 Hz, 2H); 13C NMR (75 MHz, MeOD)
d 130.7, 70.9, 67.6; HRMS (EI) Calcd for C6H8O3
(M+ꢀH2O), 128.0473; Found, 128.0455.
3.2.3.5. (1S,2S)-3,4-Dibromo-cyclohexa-3-ene-1,2-diol
(36). Diol 27 (0.38 g, 1.47 mmol, 1 equiv) was dissolved
in 6 mL MeOH, and the round-bottomed flask containing the
solution was subsequently placed into an ice/NaCl bath.
Potassium azodicarboxylate (0.93 g, 4.27 mmol, 3 equiv)
was added in two portions to the methanolic solution. Acetic
acid (0.85 mL, 12.78 mmol, 9 equiv) in 2 mL MeOH was
added dropwise over 40 min. The reaction flask was allowed
to warm to room temperature overnight (15 h). The reaction
was quenched by adding 2 mL saturated Na2CO3 solution
and stirring for 20 min. Methanol was removed under
reduced pressure and the residue diluted with 10 mL EtOAc.
The layers were separated and the aqueous phase was ex-
tracted with 3ꢂ10 mL EtOAc. The combined organic layers
were washed with brine, dried over MgSO4, and treated with
activated charcoal. Filtration and concentration of the filtrate
under reduced pressure afforded 36 as a white crystalline
solid (0.367 g, 95%). Mp 175–176 ꢁC; [a]D21 ꢀ50.4
(c 0.75, MeOH); Rf 0.23 (Hex/EtOAc, 1:1); IR (KBr pellet)
n 3246, 1626 cmꢀ1; 1H NMR (300 MHz, acetone-d6) d 4.61
(d, J¼6 Hz, 1H), 4.26 (s, 1H), 3.96–3.84 (m, 2H), 2.79–2.51
(m, 2H), 2.05–1.92 (m, 1H), 1.85–1.73 (m, 1H); 13C NMR
(75 MHz, acetone-d6) d 127.1, 124.9, 73.5, 68.25, 35.2,
26.9; HRMS (EI) Calcd for C6H8Br2O2, 271.8872; Found,
271.8871; Anal. Calcd for C6H8Br2O2: C, 26.50; H, 2.97.
Found: C, 27.34; H, 3.16.
3.3. General procedure for the formation of Mosher
ester derivative 39
Alcohol 38 (20 mg, 0.076 mmol, 1 equiv) was transferred
to a flame-dried round-bottomed flask containing magnetic
stirring bar under an argon atmosphere. Anhydrous triethyl-
amine (17 mL) was added followed by 4-dimethylaminopyr-
idine (4.8 mg, 0.038 mmol, 0.5 equiv). (R)-(ꢀ)-a-Methoxy-
a-trifluoromethyl-phenylacetic acid chloride (23 mL,
0.11 mmol, 1.5 equiv) was added dropwise. Within minutes
a white precipitate was observed. The reaction was stirred
overnight. The reaction mixture was then diluted with
5 mL methylene chloride, transferred to a separatory funnel,
and washed with 5 mL saturated solution of sodium bicar-
bonate. The layers were separated, the organic layer dried
(MgSO4), and the solvent evaporated to provide the ester as
a crude oil. The compound was purified by flash column
chromatography (pentane/Et2O, 10:1) to afford the ester as
a clear and colorless oil (20 mg, 57%). Physical and spectral
data matched that for the compound previously reported.16
3.2.3.6. (1S,2S)-1-[(Hexyldimethylsilyl)oxy]-3,4-dibro-
mocyclohexa-3-ene-2-ol (37). A 5-mL round-bottom flask
was charged with diol 36 (200 mg, 0.74 mmol, 1 equiv),
imidazole (65 mg, 0.96 mmol, 1.3 equiv), and 1 mL anhy-
drous dimethylformamide. The flask was cooled externally
to ꢀ30 ꢁC, then hexyldimethylsilyl chloride (0.15 mL,
0.78 mmol, 1.05 equiv) was added. The mixture was stirred
at ꢀ30 ꢁC for 1 h and then the reaction flask was placed in
a freezer (ꢀ18 ꢁC) for 21 h. The mixture was allowed to
warm to room temperature and diluted with 50 mL ether,
washed with 10ꢂ1 mL distilled H2O, brine, and dried over
MgSO4. After filtration, the filtrate was concentrated under
reduced pressure. The crude silyl ether was purified by flash
column chromatography (pentane/Et2O, 10:1) to give 37 as
a clear and colorless oil (0.26 g, 86%). [a]2D1 ꢀ41.1
(c 0.75, MeOH); Rf 0.23 (pentane/Et2O, 10:1); IR (film)
Rf 0.46 (pentane/Et2O, 10:1); IR (film) n 2948, 2867, 1745,
1
1463, 1450, 1379, 1263, 1169 cmꢀ1; H NMR (300 MHz,
CDCl3) d 7.60 (m, 2H), 7.40 (m, 3H), 5.12 (m, 1H), 3.80
(m, 1H), 3.55 (m, 3H), 1.75–1.55 (m, 7H), 1.5–1.2 (m,
2H), 0.88 (dd, J¼6.8, 5.2 Hz, 6H), 0.81 (d, J¼4.1 Hz, 6H),
0 (s, 3H), ꢀ0.10 (s, 3H); 19F NMR (188 MHz, CDCl3)
d ꢀ72.4 ppm. Lit.15: 19F NMR (188 MHz, CDCl3) d
ꢀ72.8 ppm.
Acknowledgements
We are indebted to the following agencies for generous
support of this work: National Science and Engineering
Research Council (NSERC); the Canadian Foundation for
Innovation; the Ontario Innovation Trust; Brock University;
the donors of the Peteroleum Research Fund, administered
by the American Chemical Society (PRF-38075-AC);
TDC Research Inc.; and TDC Research Foundation. We
thank Brock University for providing a graduate fellowship
for K.J.F. We are also grateful to Dr. Gregg Whited
(Genencor International, Inc.) and Dipl. Ing. Hannes Leisch
(Brock University) for their generous help and discussions
regarding whole-cell fermentations.
n 3547, 2958, 2868, 1628 cmꢀ1 1H NMR (300 MHz,
;
CDCl3) d 4.26–4.17 (m, 1H), 4.03–3.93 (m, 1H), 2.84 (d,
J¼4 Hz, 1H), 2.77–2.64 (m, 1H), 2.63–2.48 (m, 1H),
2.10–1.9 (m, 1H), 1.77–1.57 (m, 2H), 0.95–0.84 (m, 13H),
0.17 (s, 6H); 13C NMR (75 MHz, CDCl3) d 130.8,
127.8, 122.9, 74.1, 73.6, 69.6, 35.1, 34.1, 27.2, 24.8,
20.2, 20.0, 18.5, 18.4; HRMS (EI) Calcd for C14H26Br2O2Si,
328.9032; Found, 328.9026; Anal. Calcd for
C14H26Br2O2Si: C, 40.59; H, 6.33. Found: C, 40.96; H, 6.36.