Mayer et al.
367
rac-erythro-8-Nonene-3,4-diol (rac-erythro-2)
Method C: To a vigorously stirred solution of the alkene
(40 mmol) in anhydrous CH2Cl2 (400 mL) was added
NaH2PO4 (ca. 2.6 equiv). After the mixture was stirred for
15 min at room temperature, it was cooled to 0°C and m-
CPBA (1.05 equiv) was added slowly. The reaction was allowed
to warm to room temperature and stirred for an additional
8 h. The white suspension was filtered and the resulting so-
lution was treated with 10% aq Na2S2O5 (100 mL) to de-
stroy the excess of peracid. The resulting two-phase system
was stirred for 30 min, the layers were separated and the or-
ganic phase was washed with sat. aq NaHCO3 (50 mL). The
organic phase was dried and evaporated. Kugelrohr distilla-
tion afforded pure oxiranes rac-cis-1 and rac-trans-1. De-
tails and spectroscopic data are given below.
Method D was employed using oxirane rac-trans-1 (0.3 g,
2.1 mmol). Flash chromatography (p.e.–EtOAc, 3:1) gave
pure erythro-8-nonene-3,4-diol rac-erythro-2 (0.21 g, 63%).
Rf (p.e.–EtOAc, 1:1) = 0.45 (detection I). Spectroscopic data
were in full agreement with those previously reported (16).
HRMS calcd. for C9H18O2: 158.1307 [M+]; found: 158.1303
[M+].
General procedure for preparative-scale biohydrolysis of
rac-cis-1 and rac-trans-1
Racemic epoxides rac-cis-1 (0.7 g, 5 mmol) and rac-trans-1
(0.3 g, 2.14 mmol) were hydrolyzed using rehydrated
lyophilized microbial cells (1 g Mycobacterium paraffinicum
NCIMB 10420 for rac-cis-1, 0.4 g of Rhodococcus ruber
DSM 44539 for rac-trans-1) in Tris-buffer (30 mL for rac-
cis-1, 15 mL for rac-trans-1, 0.05 M, pH 8.0) on an orbit
shaker (120 rpm) at 30°C. When the starting material was
consumed (after 6 h for rac-cis-1, 4 h for rac-trans-1, as
judged by TLC and GLC), the mixture was extracted contin-
uously with CH2Cl2 for 24 h. The organic layers were dried
and evaporated. The residue was flash chromatographed
(p.e.–EtOAc, 3:1) to give (3R,4R)-2 (0.66 g, 83%, ee 92%)
or (3R,4S)-2 (0.20 g, 58%, ee 72%). Spectroscopic data of
these products matched those of material obtained by acidic
hydrolysis of the corresponding rac-oxiranes. Elemental
analysis of (3R,4R)-2: Anal. calcd. for C9H18O2: C 68.30,
H 11.45; found: C 68.35, H 11.46. Elemental analysis of
(3R,4S)-2: Anal. calcd. for C9H18O2: C 68.30, H 11.45;
found: C 68.38, H 11.48.
cis-3,4-Epoxynon-8-ene (rac-cis-1)
Method C was employed using (Z)-6 (5 g, 40.3 mmol).
Kugelrohr distillation gave rac-cis-1 as a colorless liquid
(3.9 g, 69%). Rf (p.e.–EtOAc, 5:1) = 0.55 (detection I). bp20mbar
1
(Kugelrohr): 80–90°C. H NMR (360.13 MHz, CDCl3) δ:
1.01 (t, J = 7.0, 3H), 1.49–1.58 (m, 6H), 2.08–2.12 (m, 2H),
2.84–2.92 (m, 2H), 4.94–5.04 (m, 2H), 5.75–5.83 (m, 1H).
13C NMR (90.56 MHz, CDCl3) δ: 10.6, 21.2, 25.9, 27.2,
33.6, 57.1, 58.4, 114.9, 138.4. Anal. calcd. for C9H16O:
C 77.05, 11.50; found: C 77.12, H 11.51.
trans-3,4-Epoxynon-8-ene (rac-trans-1)
Method C was employed using (E)-6 (6 g, 48.4 mmol).
Kugelrohr distillation gave rac-trans-1 as a colorless liquid
(5.1 g, 75%). Rf (p.e.–EtOAc, 5:1) = 0.65 (detection I). bp20mbar
1
General procedure for the synthesis of (+)-exo- and (–)-
endo-brevicomin [(+)-exo- and (–)-endo-3, respectively]
via Wacker-oxidation of diols (3R,4R)-2 and (3R,4S)-2,
respectively, following Method E
(Kugelrohr): 85–95°C. H NMR (360.13 MHz, CDCl3) δ:
0.98 (t, J = 7.0, 3H), 1.48–1.58 (m, 6H), 2.09 (d, J = 5.9,
2H), 2.62–2.67 (m, 2H), 4.94–5.03 (m, 2H), 5.76–5.84 (m,
1H). 13C NMR (90.56 MHz, CDCl3) δ: 9.94, 25.2, 25.4,
31.5, 33.5, 58.4, 60.0, 114.8, 138.4. Anal. calcd. for C9H16O:
C 77.05, 11.50; found: C 77.08, H 11.55.
Method E: Nonracemic diol (3R,4R)-2 or (3R,4S)-2
(3.2 mmol) was dissolved in anhydrous 1,2-dimethoxyethane
(10 mL). The solution was stirred at room temperature.
PdCl2 (0.10 g, 0.57 mmol) and CuCl2 (0.43 g, 3.2 mmol)
were added and stirring was continued for 10 h. The brown
solution was diluted with H2O and Et2O (10 mL each). After
phase separation, the aqueous layer was extracted with Et2O
(2 × 10 mL). The combined organic phases were dried
(Na2SO4) and concentrated. The residue was purified by flash
chromatography. Details and spectroscopic data are given
below.
General procedure for the synthesis of reference material
for racemic diols rac-threo-2 and rac-erythro-2
The rac-diols rac-threo-2 and rac-erythro-2 were obtained
by acid-catalysed hydrolysis of rac-cis-1 and rac-trans-1
following Method D.
Method D: Racemic diols rac-threo-2 and rac-erythro-2
were obtained by hydrolysis of the corresponding racemic
oxiranes of rac-cis-1 and rac-trans-1 (1.1 mmol) in a mix-
ture of water and THF (10 mL, 4:1) under acidic conditions
(6 M H2SO4, 10 drops). After the reaction reached completion
(2 h), the solution was extracted with EtOAc (2 × 10 mL).
The combined organic layers were dried and concentrated.
The residue was purified by flash chromatography. Details
and spectroscopic data are given below.
(+)-exo-Brevicomin ((+)-exo-3)
Method E was employed using (3R,4R)-2 (0.5 g, 3.2 mmol).
Flash chromatography (pentane–Et2O, 10:1) gave pure (+)-
exo-3 (0.37 g, 75%, ee 92%). Rf (p.e.–EtOAc, 5:1) = 0.54
1
(detection I). H NMR (360.13 MHz, CDCl3) δ: 0.92 (t, J =
7.4, 3H), 1.43 (s, 3H), 1.57–1.84 (m, 8H), 3.94 (t, J = 6.4,
1H), 4.15 (s, 1H,). 13C NMR (90.56 MHz, CDCl3) δ: 9.8,
17.2, 25.1, 28.0, 28.6, 35.0, 78.4, 81.2, 107.7. HRMS calcd.
for C9H16O2: 156.1150 [M+]; found: 156.1145 [M+].
rac-threo-8-Nonene-3,4-diol (rac-threo-2)
Method D was employed using oxirane rac-cis-1 (0.3 g,
2.1 mmol). Flash chromatography (p.e.–EtOAc, 3:1) gave pure
rac-threo-8-nonene-3,4-diol rac-threo-2 (0.25 g, 74%). Rf (p.e.–
EtOAc, 1:1) = 0.42 (detection I). Spectroscopic data were in
full agreement with those previously reported (16). HRMS
calcd. for C9H18O2: 158.1307 [M+]; found: 158.1314 [M+].
(–)-endo-Brevicomin ((–)-endo-3)
Method E was employed using (3R,4S)-2 (0.15 g,
0.95 mmol). Flash chromatography (pentane–Et2O, 10:1) gave
pure (–)-endo-3 (0.09 g, 61%, ee 72%). Rf (p.e.–EtOAc, 5:1) =
0.57 (detection I). 1H NMR (360.13 MHz, CDCl3) δ: 0.96 (t,
© 2002 NRC Canada