3720 J . Org. Chem., Vol. 64, No. 10, 1999
Hu et al.
Sch em e 3
Exp er im en ta l Section
Gen er a l Ch em ica l P r oced u r es. THF and diethyl ether
were distilled from sodium-benzophenone ketyl. Dicyclohexyl-
amine [(c-Hex)2NH] was freshly distilled from CaH2 prior to
use. Allyl chloride was freshly distilled over P2O5 prior to use.
Undecanyl aldehyde was distilled prior to use. The lIpc2BOMe
and 9-BBN were purchased from Aldrich and used without
purification. Moisture- and air-sensitive reactions were con-
ducted under argon in vacuum-dried glassware. A nitrogen
glovebag was used to weigh moisture-sensitive compounds.
Syringes and cannulas were used to transfer air-sensitive
reagents.13 Unless otherwise stated, standard workup refers
the combination of organic extracts, washing with ice-cold
brine, drying over anhydrous MgSO4, and concentration in
vacuo. 1H NMR and 13C NMR spectra were recorded at 400
and 100 MHz, respectively. GC analyses were conducted using
a 30-m × 0.25-mm i.d. fused silica column coated with DB-1
with FID detection.
cis-(3R,4R)-3,4-Ep oxy-1-tetr a d ecen e, 4. To a stirred and
l
cooled (-95 °C) mixture of Ipc2BOMe (11.5 mmol) and allyl
chloride (15 mmol) in anhydrous ether (50 mL) was added a
solution of LiN(c-Hex)2 (15 mmol) in THF (25 mL). After
stirring for 1 h, BF3‚OEt2 (30 mmol) and undecanyl aldehyde
(11.5 mmol) were added sequentially. The reaction was
continued at -95 °C for 4 h. Solvents were removed in vacuo
at room temperature, and the residue was triturated with
n-pentane (40 mL) and allowed to settle (12 h). The superna-
tant was transferred to another predried flask by cannula. The
residue was further treated with pentane (2 × 30 mL), and
the pentane extracts were combined. Removal of pentane in
vacuo furnished a semisolid.
Since the boron of dicyclohexylborane is more sterically
encumbered, it would not be expected to coordinate as
strongly with the epoxide oxygen lone pair electrons.
Therefore, ring opening should be a slower process.7b
Hydroboration using HB(c-Hex)2 followed by addition of
NaOH/H2O2 also failed to produce 3. The failure of
hydroboration of 4 in the foregoing reactions could be
because of complications during the oxidation due to the
sensitivity of the epoxide to strong base.8 Thus, we
reexamined hydroboration of 4 using dicyclohexylborane
in several solvents and determined that the reaction
proceeded well in THF but was much slower in Et2O,
pentane, or toluene. Oxidation with various reagents
gave 3. Surprisingly, NaOAc/H2O2, which is useful for
organoboranes with base-sensitive functional groups did
not give a good result. Sodium perborate9 is the reagent
of choice providing 3 in 67% yield (Scheme 3).10
Oxid a tion of Bor on In ter m ed ia te. The residue obtained
from chloroallylboration reaction was dissolved in THF (20 mL)
with stirring and cooled to 0 °C. Then, 3 M NaOH (12 mL)
and 30% H2O2 (12 mL) were sequentially added. The reaction
mixture was allowed to warm to room temperature (14 h).
Standard workup followed by flash chromatography yielded a
colorless liquid 4 (1.32 g, 63% yield). [R]23 +21.09 (c ) 8.81,
D
CH2Cl2); 13C NMR (CDCl3, ppm) 132.78, 120.13, 58.79, 57.17,
31.90, 29.58, 29.53, 29.42, 29.30, 27.75, 26.29, 22.66, 14.04.
1H NMR (CDCl3, ppm) 5.69 (ddd, J ) 17.2, 10.4, 7.2 Hz, 1H),
5.46 (ddd, J ) 17.2, 1, 1 Hz, 1H), 5.34 (ddd, J ) 10.2, 1, 1 Hz,
1H), 3.39 (dd, J ) 7.2, 4.3 Hz, 1H), 3.06 (m, 1H), 1.58-1.26
(m, 18H), 0.87 (t, J ) 6.8 Hz, 3H); CIMS m/z (isobutane, rel
intensity) 211 (M+ + 1, 18), 169 (100). Anal. Calcd for
Two recrystallizations from 1% ether in hexane solu-
tion yielded 3 (mp: 38.5-39.5 °C) in enantiopure form.11
C. Syn th esis of (+)-Disp a r lu r e. Tosylation of cis-3,4-
epoxy alcohol 3 with tosyl chloride in pyridine for 2 days
gave a low yield of 2 (50% yield). However, reaction of 3
with tosyl chloride and powdered potassium hydroxide
in ethyl ether gave a good yield of 2 (86%). Cuprate-
mediated alkylation of 2 furnished with (+)-1 in 76%
yield (Scheme 3). Enantiomeric purity of (+)-1 was
determined to be g99.5% by Oliver’s method.12
C
14H26O: C, 79.94; H, 12.46. Found: C, 79.80; H, 12.55.
Enantiomeric purity was determined to be 94% by 1HNMR
analysis using chiral shift reagent Eu(hfc)3.
cis-(3R,4R)-3,4-E p oxyt et r a d eca n -1-ol, 3. Dicyclohexyl-
borane is prepared from freshly distilled cyclohexene and BH3‚
SMe2. Further purification by sublimation is performed. A
solution of epoxide 4 (420 mg, 2 mmol) in THF (1 mL) was
added to 2 mmol of dicyclohexylborane-THF solution (2 mL)
via syringe while stirring. Stirring was continued for 4 h at
room temperature. The reaction was quenched by addition of
910 mg of NaBO3‚H2O and 0.5 mL of H2O. The mixture was
stirred overnight, and then 4 g of anhydrous K2CO3 was added.
After 2 h, the mixture was diluted with 15 mL of anhydrous
Et2O. Solid was removed by filtration and washed with Et2O.
Concentration of the filtrate in vacuo, followed by flash
chromatography using hexane:Et2O, 7:3, as eluant yielded 291
mg of 3 (67% yield), mp 33-37.5 °C. Two cycles of recrystal-
Con clu sion s
cis-Vinyl epoxide 4 (94% ee) was generated by chloro-
allylboration of undecanaldehyde using (Z)-γ-chloroal-
lylborane, 5. Subsequent hydroboration using dicyclo-
hexylborane in THF followed by sodium perborate
oxidation gave cis-epoxy alcohol 3 which was converted
to (+)-1 in overall yield of 27% and g99.5% ee.
lization from 1% Et2O in hexane gave mp 37.7-38.5 °C. [R]23
D
-8.34 (c ) 6.32, Et2O); 13C NMR (CDCl3, ppm) 60.81, 56.68,
54.94, 31.88, 30.68, 29.66, 29.56, 29.53, 29.49, 29.28, 27.96,
(8) Matteson, D. S. Stereodirected Synthesis with Organoboranes;
Springer-Verlag: New York, 1995.
(9) Kabalka, G. W.; Shoup, T. M.; Goudgaon, N. M. J . Org. Chem.
1989, 54, 5930.
1
26.46, 22.63, 14.01. H NMR (CDCl3, ppm) 3.86 (m, 2H), 3.09
(dt, J ) 8.0, 4.4 Hz, 1H), 2.93 (td, J ) 5.6, 4.4 Hz, 1H), 1.92-
1.26 (m, 21H), 0.87 (t, J ) 6.8 Hz, 3H). IR (film) 3308, 2917,
2850, 1417, 1068, 1047, 843 cm-1. CIMS m/z (isobutane, rel
intensity) 229 (M+ + 1, 100), 211 [(M+ - 18) + 1, 95]. Anal.
Calcd for C14H28O2: C, 73.63; H, 12.36. Found: C, 73.80; H,
(10) For
a preliminary account of hydroboration of some vinyl
epoxides, see: Hu, S.; J ayaraman, S.; Oehlschlager, A. C. Tetrahedron
Lett. 1998, 39, 8059.
(11) As the enantiomeric purity of (+)-1 is g99.5% based on the
method of Oliver (see ref 12), it is reasonable to assume 3 possessing
enantiomeric purity of g99.5%.
(13) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
(12) Oliver, J . E.; Waters, R. M. J . Chem. Ecol. 1995, 21, 199.
Organic Synthesis via Boranes; Wiley-Interscience: New York, 1975.