The Journal of Organic Chemistry
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the reaction mixture was allowed to stir for 3 h. After addition of a satd
NH4Cl (aq), the product was extracted twice with Et2O. The
combined organic layers were washed with brine, dried over MgSO4,
and concentrated in vacuo. Purification through flash chromatography
(SiO2, pentane/EtOAc) gave the corresponding allylic alcohol in
approximately quantitative yields.
3-(4-Chlorophenyl)cyclohex-2-enol (1d). Experimental data were
in accordance with those reported in the previous literature.34 1H
NMR (CDCl3, 400 MHz): δ = 7.35−7.28 (m, 4H), 6.14−6.09 (m,
1H), 4.40 (s, 1H), 2.47−2.29 (m, 2H), 2.00−1.87 (m, 2H), 1.79−1.64
(m, 2H). No chiral separation found on GC or HPLC.
3-(4-Methoxyphenyl)cyclohex-2-enol (1e). Experimental data were
in accordance with those reported in the previous literature.29 1H
NMR (CDCl3, 400 MHz): δ = 7.35 (d, 2H, J = 8.9 Hz), 6.86 (d, 2H, J
= 8.9 Hz), 6.09−6.02 (m, 1H), 4.43−4.33 (m, 1H), 3.81 (s, 3H),
2.50−2.40 (m, 1H), 2.38−2.29 (m, 1H), 1.98−1.85 (m, 2H), 1.79−
1.63 (m, 2H). Chiral separation: GC: IVADEX-I, 100−1 °C/min−180
°C, tR1 = 79.8 min (S), tR2 = 80.3 min (R).
3-(Phenylsulfonyl)cyclohex-2-enol (1f). Experimental data were in
accordance with those reported in the previous literature.21b 1H NMR
(CDCl3, 400 MHz): δ = 7.44−7.39 (m, 2H), 7.36−7.28 (m, 3H),
5.74−5.71 (m, 1H), 4.28−4.21 (m, 1H), 2.20−2.03 (m, 2H), 1.90−
1.74 (m, 2H), 1.68−1.58 (m, 2H). Chiral separation: HPLC:
Chiralpak OJ column, 95:5 isohexane/i-PrOH, 0.5 mL·min−1, 30 °C,
211 nm, tR1 = 23 min (R), tR2 = 24.6 min (S).
3-Iodocyclohex-2-enol (1g). Experimental data were in accordance
with those previous reported.35 1H NMR (CDCl3, 400 MHz): δ =
6.46−6.42 (m, 1H), 4.19−4.13 (m, 1H), 2.60−2.41 (m, 2H), 1.95−
1.87 (m, 2H), 1.86−1.76 (m, 1H), 1.69−1.57 (m, 2H). Chiral
separation: GC: IVADEX-I, 70−1 °C/min−140 °C, tR1 = 57.1 min
(R), tR2 = 60.2 min (S).
3-Undecylcyclohex-2-enol (1h). Experimental data were in
accordance with those reported in the previous literature.32 1H
NMR (CDCl3, 400 MHz): δ = 5.52−5.48 (m, 1H), 4.21−4.17 (m,
1H), 2.05−1.89 (m, 4H), 1.86−1.70 (m, 2H), 1.64−1.55 (m, 2H),
1.47−1.36 (m, 2H), 1.34−1.24 (m, 16H), 0.92−0.89 (m, 3H). No
chiral separation found on GC or HPLC.
3-(Phenylsulfonyl)cyclopent-2-enol (1i). Experimental data were in
accordance with those reported in the previous literature.21b 1H NMR
(CDCl3, 400 MHz): δ = 7.96−7.91 (m, 2H), 7.72−7.65 (m, 1H),
7.61−7.55 (m, 2H), 6.69−6.65 (m, 1H), 5.05−4.97 (m, 1H), 2.73−
2..63 (m, 1H), 2.56−2.44 (m, 2H), 1.97−1.82 (m, 2H). HPLC:
Chiralpak IA column, 10% i-PrOH/isohexane, 0.5 mL·min−1, 30 °C,
211 nm, tR1 = 50 min (R), tR2 = 57 min (S).
3-Hydroxycyclopent-1-enecarbonitrile (1j). Experimental data
were in accordance with those reported in the previous literature.33
1H NMR (CDCl3, 400 MHz): δ = 6.63−6.60 (m, 1H), 5.04−4.96 (m,
1H), 2.81−2.71 (m, 1H), 2.60−2.49 (m, 1H), 2.46−2.36 (m, 1H),
1.88−1.78 (m, 2H). HPLC: Chiralpak IA column, 5% i-PrOH/
isohexane, 0.5 mL·min−1, 30 °C, 211 nm, tR1 = 30 min (R), tR2 = 33
min (S).
THF, 0.0125 mmol) was added to the reaction mixture. The reaction
turned orange. After approximately 5 min of stirring, racemic alcohol 1
(0.25 mmol) dissolved in dry toluene (0.5 mL) was added to the
reaction mixture. After an additional 5 min, isopropenyl acetate (110
μL, 2 mmol) was added. The reaction was heated to indicated
temperature. After 24 h, the reaction mixture was filtered and
concentrated.
(R)-3-Phenylcyclohex-2-enyl Acetate (2a). The reaction was
performed according to method A using the enzyme preparation
Amano PS-IM. Excess p-chlorophenyl acetate was hydrolyzed by
stirring the concentrated residue in a NaHCO3-saturated 4:1 mixture
of MeOH/H2O for 1 h. SiO2 chromatography (pentane/EtOAc 20:1)
was performed to obtain pure product in 87% yield (47 mg) and 97%
ee. Experimental data were in accordance with those reported in the
previous literature.36 1H NMR (CDCl3, 400 MHz): δ = 7.44−7.40 (m,
2H), 7.37−7.28 (m, 3H), 6.10−6.04 (m, 1H), 5.48 (s, 1H), 2.59−2.36
(m, 2H), 2.07 (s, 3H), 1.95−1.85 (m, 2H), 1.82−1.74 (m, 2H). Chiral
separation: GC: IVADEX-I, 100−1 °C/min−180 °C, tR1 = 55.5 min
(S), tR2 = 56.4 min (R), 97% ee.
The NMR data for side product 4a were in accordance with those
reported in the previous literature.37 Mixture of two diastereomers. 1H
NMR (CDCl3, 400 MHz): δ = 7.46−4.42 (m, 4H), 7.36−7.30 (m,
4H), 6.21−6.14 (m, 2H), 4.34−4.24 (m, 2H), 2.55−2.46 (m, 2H),
2.44−2.35 (m, 2H), 2.06−1.91 (m, 4H), 1.86−1.72 (m, 4H).
(R)-3-(4-Chlorophenyl)cyclohex-2-enyl Acetate (2d). The reaction
performed according to method A using the enzyme preparation
Amano PS-IM. Compound isolated after column chromatography
1
(SiO2, pentane/EtOAc 19:1) in 84% yield (53 mg) and 96% ee. H
NMR (CDCl3, 400 MHz): δ = 7.39−7.27 (m, 4H), 6.09−6.05 (m,
1H), 5.47−5.41 (m, 1H), 2.51−2.45 (m, 1H), 2.39−2.30 (m, 1H) 2.08
(s, 3H), 1.95−1.90 (m, 2H), 1.79−1.75 (m, 2H). 13C NMR (CDCl3,
100 MHz): δ = 171.0, 141.2, 139.6, 133.6, 128.6, 126.7, 122.3 69.0,
28.0, 27.4, 21.5, 19.5. HR-MS (ESI): calcd for C14H15ClO2+ 273.0652,
found 273.0653 [M + Na]+. Chiral separation: GC: IVADEX-I, 100−1
°C/min−180 °C, tR1 = 75.7 min (S), tR2 = 76.2 min (R), [α]22
+85.4 (c 0.80, CHCl3), 96% ee.
=
D
(R)-3-(4-Methoxyphenyl)cyclohex-2-enyl Acetate (2e). The reac-
tion was performed according to method A using the enzyme
preparation Amano PS-IM. After 24 h, the reaction mixture consisted
of 41% 2e, 31% of the ketone adduct, and 28% of ether dimer. No
enantiomeric excess was obtained. The compound was not isolated. 1H
NMR (CDCl3, 400 MHz): δ = 7.38−7.33 (m, 2H), 6.88−6.83 (m,
2H), 6.03−6.00 (m. 1H), 5.47−5.42 (m, 1H), 3.81 (s, 3H), 2.54−2.46
(m, 1H), 2.39−2.30 (m, 1H), 2.07 (s, 3H), 1.94−1.87 (m, 2H), 1.82−
1.75 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ = 171.0, 159.4, 141.6,
133.6, 126.6, 120.7, 113.8, 69.2, 55.4, 28.1, 27.5, 21.6, 19.5. HR-MS
(CI): calcd for C15H18O3 246.1256, found 246.1255 [M]+. Chiral
separation: GC: IVADEX-I, 100−1 °C/min−200 °C, tR1 = 81.1 min
(S), tR2 = 82.5 min (R), 0% ee.
(R)-3-(Phenylsulfonyl)cyclohex-2-enyl Acetate (2f). The reaction
was performed according to method A using the enzyme preparation
Amano PS-IM. The compound was isolated after column chromatog-
General Procedure for Kinetic Resolution. Substrate (0.2
mmol), isopropenyl acetate (2 equiv), lipase (25 mg/mmol), and
Na2CO3 (1 equiv) was dissolved in dry toluene (0.8 mL) and stirred at
room temperature. Aliquots (50 μL) were taken by syringe at the
indicated time and filtered with EtOAc through a Celite plug. After
evaporation of the solvent, the enantiomeric excess and conversion
were check by HPLC and NMR spectroscopy, respectively.
General Procedure Dynamic Kinetic Resolution. Method A.
Shvo’s complex (A) (13.6 mg, 0.0125 mmol), lipase (12.5 mg, 50 mg/
mmol substrate), and the racemic alcohol 1 (0.25 mmol) were added
to a dry Schlenk tube under argon atmosphere. Dry toluene (1 mL)
and then p-chlorophenyl acetate (0.875 mmol) were added. The
reaction was heated to 60 °C. After 24 h, the mixture was filtered
through cotton and concentrated under vacuum.
1
raphy (SiO2, pentane/EtOAc 4:1) in 82% yield (27 mg), 94% ee. H
NMR (CDCl3, 400 MHz): δ = 7.90−7.84 (m, 2H), 7.67−7.61 (m,
1H), 7.58−7.51 (m, 2H) 6.93−6.88 (m, 1H), 5.46−5.40 (m, 1H),
2.32−2.22 (m, 1H), 2.19−2.11 (m, 1H), 2.08 (s, 3H), 1.93−1.59 (m,
4H). 13C NMR (CDCl3, 100 MHz): δ = 170.4, 144.5, 138.7, 134.7,
133.7, 129.4, 128.4, 67.4, 27.2, 23.0, 21.2, 19.2. HR-MS (ESI): calcd
for C14H16NaO4S+ 303.0671, found 303.0662 [M + Na]+. Chiral
separation: HPLC: Chiralpak OJ column, 97:3 isohexane/i-PrOH, 0.5
mL·min−1, 30 °C, 211 nm, tR1 = 22 min (R), tR2 = 23 min (S). [α]20
+95.0 (c 0.92, CHCl3), 94% ee.
=
D
(R)-3-Iodocyclohex-2-enyl Acetate (2g). The reaction was
performed at 30 °C according to method B using the enzyme
preparation Amano PS-IM. Compound isolated after column
chromatography (SiO2, pentane/EtOAc 20:1) in 90% yield (58 mg).
>99% ee. Experimental data were in accordance with those previous
reported.35 1H NMR (CDCl3, 400 MHz): δ = 6.46−6.42 (m, 1H),
4.19−4.13 (m, 1H), 2.60−2.41 (m, 2H), 1.95−1.87 (m, 2H), 1.86−
1.76 (m, 1H), 1.69−1.57 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ =
Method B. Ruthenium complex B (η5C5Ph5)Ru(CO)2Cl (8 mg,
0.0125 mmol), lipase (6.25 mg, 25 mg/mmol substrate), and Na2CO3
(26.5 mg, 0.25 mmol) were added to a dry Schlenk tube under argon
atmosphere. Dry toluene (0.5 mL) was added, and the resulting yellow
solution was stirred. A THF solution of t-BuOK (25 μL, 0.5 M in dry
12118
dx.doi.org/10.1021/jo402086z | J. Org. Chem. 2013, 78, 12114−12120