7750 J . Org. Chem., Vol. 64, No. 21, 1999
Hamed et al.
and concentrated to yield an oil. Distillation under vacuum
provided 7.7 g (0.079 mol) of 3-hexyn-2-ol, 73% yield. Exami-
nation of the 1H NMR spectrum in the presence of Eu(hfc)3,
indicated an enantiomeric mixture containing 84% (R)
(68% ee).
stirring was continued for 48 h at room temperature, followed
by dilution with 100 mL of CH2Cl2 and washing with 30 mL
of water. The organic layer was dried over anhydrous MgSO4
and distilled to remove the solvent. Analysis of the residue by
GLC and NMR showed the presence of only one product that
was identified by NMR spectroscopy as 4-methoxy-(Z)-2-
pentene (3a ′).
The enantiomeric purity of 3a ′ was 68%. As described next
its absolute configuration was found to be R by converting pure
sample of 3a ′, obtained by preparative GLC, to 4-methoxy-2-
pentanone (5a ′).
P d (OAc)2-Ca t a lyzed Oxid a t ion of 4-Met h oxy-(Z)-2-
p en ten e (Z-3a ′). For procedure, see Pd(OAc)2-catalyzed oxida-
tion of 4-phenyl-(Z)-2-pentene. Comparison of the 1H NMR
spectrum of the 5a ′ product with that of an authentic sample,
both in the presence of Eu(hfc)3, showed that the absolute
configuration was R.
P r ep a r a tion of (R)-(-)-(Z)-3-Hexen -2-ol (3b). A low-
pressure hydrogenation apparatus was charged with 10 mL
of hexane, 3.5 mL (3.2 g, 0.032 mol) of (R)-(+)-3-hexyn-2-ol,
0.2 g of Pd on CaCO3 poisoned with lead (Lindlar’s catalyst),
and 20 drops of quinoline. The apparatus was evacuated, and
hydrogen was admitted to a pressure slightly above 1 atm.
The contents of the flask was shaken until absorption of
hydrogen stopped. The catalyst was removed by filtration,
hexane was distilled off, and the residue upon distillation
under vacuum produced 2.2 g (0.022 mol, 71% yield) of
colorless liquid which was found by GLC analysis to be a 98%
1
pure Z isomer. H NMR study of the product in the presence
of Eu(hfc)3 indicated the sample was 83% (R) (66% ee).
Li2P dCl4-Catalyzed P h en ylation of (R)-(+)-(Z)-3-P en ten -
2-ol. To a stirred solution of 0.1 M Li2PdCl4 in methanol (15.0
mL) was added 0.5 mL (3.7 mmol) of Et3N, 0.5 g (3.7 mmol) of
CuCl2, 1.1 g (3.5 mmol) of PhHgCl, and 0.35 mL (0.3 g, 3.5
mmol) of (R)-(Z)-3-penten-2-ol (ee ) 53%). After stirring for 2
h at room temperature, the reaction was diluted with water.
The precipitate was removed by filtration, and the filtrate and
the precipitate were extracted with ether (3 × 30 mL). The
ether layers were combined and dried over MgSO4, and solvent
was removed under vacuum. The residue was purified twice
by column chromatography (silica gel, 8/2 hexane/ether) to give
0.47 g (84% yield) of 4-phenyl-2-pentanone. Lanthanide shift
determination showed the presence of 65% R (30% ee).
P h en yla tion of (S)-(Z)-3-P en ten -2-ol (ee ) 74%) in th e
P r esen ce of High [LiCl]. A 100-mL two-necked round-
bottom flask, containing a magnetic stirring bar and LiCl (1.6
g, 37.7 mmol) fitted with a septum-cap, was evacuated on a
vacuum line at 100 °C for 2 h. To this were added PdCl2 (0.11
g, 0.6 mmol), CuCl2 (0.67 g, 5 mmol), and 15 mL of methanol.
After stirring the solution for 30 min, PhHgCl (0.70 g, 3.5
mmol) and (S)-(Z)-3-penten-2-ol (0.35 mL, 0.30 g, 3.5 mmol)
were added. The stirring was continued for 48 h at room
temperature, and then the reaction mixture was diluted with
100 mL of CH2Cl2 and washed with 30 mL of water. The
organic layer was dried over anhydrous MgSO4 and concen-
trated under reduced pressure. Analysis of the residue by GLC
and NMR showed the presence of 4-phenyl-(Z)-2-pentene (3a ′′),
phenylbenzene, and 4-phenyl-2-pentanone (5a ′′) in relative
yields of 70%, 25%, and 5%, respectively.
Oxid a tion of (R)-(-)-(Z)-3-Hexen -2-ol (3b). The reaction
solution (50.0 L), which was (0.1 M) in K2PdCl4, 0.1 M in HCl,
and 0.1 M in benzoquinone was put into an open, round-bottom
flask. (R)-(-)-(Z)-3b (0.65 mL; 0.11 M) was gradually added
over a period of 20 min. The solution was stirred for another
20 min, followed by addition of Zn powder. After another 10
min of stirring, the mixture was extracted with ether (3 × 50
mL). The combined extracts were combined and dried over
anhydrous MgSO4. Analysis of the product by GLC and 1H
NMR showed that the product is a mixture of two compounds
5b and 5c in relative yields of 57% and 43%, respectively.
Preparative GLC yielded pure samples of 5b and 5c. The ee
of 5b and 5c were 42% and 38%, respectively.
P r ep a r a tion of (R)-(-)-MTP A Der iva tive of 4-Hyd r oxy-
2-h exa n on e (5b). The reagents were injected by a syringe into
a 1 mL conical vial fitted with a rubber septum in the following
order: dry pyridine (300 µL), carbon tetrachloride (300 µL),
(+)-MTPA-Cl (37 µL, 0.15 mmol), and 5b (11.5 mg, 0.15 mmol).
The reaction mixture was stirred at room temperature for
about 48 h. Excess 3-(dimethylethylamino)-2-propylamine (24
µL, 20 mg, 0.2 mmol) was added, and the mixture was stirred
for another 10 min. It was then diluted with ether and washed
with cold dilute HCl, cold saturated Na2CO3, and saturated
NaCl. After drying over MgSO4, the ether was removed under
vacuum. The 1H NMR spectrum of the residue was taken in
the presence of Eu(hfc)3.
P r ep a r a tion of (R)-(+)-MTP A Der iva tive of 5-Hyd r oxy-
3-h exa n on e (5c). See preparation of (R)-(+)-MTPA derivative
of 4-hydroxy-2-hexanone.
Isom er iza tion of (R)-(-)-(Z)-4-Hexen -3-ol (3c). The reac-
tion solution (25.0 mL) was 0.05 M in Li2PdCl4, 0.2 M in
benzoquinone, 2.0 M in LiCl, and 0.06 M in (R)-(-)-(Z)-(3c).
The reaction mixture was stirred for 30 min at room temper-
ature, and CH2Cl2 was used to extract the product (3 × 30
mL). The extracts were combined, dried over MgSO4, and
evaporated. A pure sample of the product was collected by
preparative gas chromatography. The product was identified
The enantiomeric purity of 3a ′′ and its absolute configura-
tion were determined by converting pure sample of 3a ′′
obtained by preparative GLC to 4-phenyl-2-pentanone (5a ′′)
as described below.
P d (OAc)2-Ca ta lyzed Oxid a tion of 4-P h en yl-(Z)-2-p en -
ten e. A 2 mL conical vial fitted with a magnetic stirring bar
and a reflux condenser was charged with acetonitrile (0.9 mL),
H2O (0.1 mL), benzoquinone (20 mg, 0.19 mmol), HClO4 (10
µL), 4 -phenyl-Z-2-pentene (3a ′′) (0.015 g, 0.1 mmol), and Pd-
(OAc)2 (0.0011 g, 0.005 mmol). The resulting solution was
stirred at 50 °C for 6 h. Then it was diluted with CH2Cl2 (5
mL), washed with water (5 mL), and dried over MgSO4. CH2-
Cl2 was removed under reduced pressure. Analysis of the
residue by 1H NMR showed the presence of one product,
4-phenyl-2-pentanone (5a ′′). Its ee was 56%, and comparison
1
by H and 13C NMR as a mixture of equal amounts of (R)-(-)-
1
(Z)-(3c) and (S)-(-)-(Z)-(3b). The ee’s were determined by H
NMR in the presence of the chiral shift reagent Eu(hfc)3.
Ack n ow led gm en t is made to the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for their support. C.M.T. thanks
the National Institutes of Health (grant no. ES04434)
for their support. The authors also thank Loyola Uni-
versity for the purchase of the VXR-300 NMR used in
this work.
1
of its H NMR spectrum with that of an authentic sample, both
in the presence of Eu(hfc)3, showed that its absolute configu-
ration was S.
Meth oxyla tion of (S)-(Z)-3-P en ten -2-ol ((S)-(Z)-3a ) (ee
) 74%) in th e P r esen ce of High [LiCl]. A 100-mL two-
necked round-bottom flask, containing a magnetic stirring bar
and LiCl (1.6 g, 37.7 mmol, 2.5 M) fitted with a septum-cap,
was evacuated on a vacuum line at 100 °C for 2 h. To this
were added PdCl2 (0.11 g, 0.6 mmol), CuCl2 or benzoquinone
(5 mmol), and 15 mL of methanol. After stirring for 30 min,
(S)-Z-3-penten-2-ol (0.35 mL, 0.30 g, 3.5 mmol) was added. The
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
and IR spectra data, as well as optical rotations, of (S)-(+)-3-
pentyn-2-ol, (R)-3-hexyn-2-ol, 3a , 3a ′, 3a ′′, 3b, 5a ′, 5a ′′, 5b,
5c (3 pages). This material is available free of charge via the
Internet at http://pubs.acs.org.
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