The Journal of Organic Chemistry
Note
−
1 1
−
78 °C was added n-BuLi (8.4 mL, 2.5 M in hexanes, 21.1 mmol)
(neat) 3430 cm ; H NMR (400 MHz, CDCl ) δ 7.29 (d, J = 8.2 Hz,
3
dropwise. The solution was allowed to stir for 20 min at −78 °C
followed by the slow addition of TIPSCl (4.9 mL, 21.1 mmol). After 2
h, the reaction was allowed to slowly warm to rt overnight and was
2H), 7.27 (d, J = 8.2 Hz, 2H), 5.93−5.79 (m, 2H), 5.32−5.26 (m,
3H), 5.12 (ddd, J = 10.5, 1.6, 1.6 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H),
4.47−4.37 (m, 1H), 4.30 (d, J = 11.2 Hz, 1H), 4.16−4.09 (m, 1H),
3.82 (s, 3H), 2.97 (m, 1H), 1.90 (ddd, J = 14.4, 8.4, 3.2 Hz, 1H), 1.73
quenched with saturated aqueous NH Cl (100 mL). The phases were
4
separated, and the aqueous layer was washed with EtOAc (3 × 100
mL). The combined organic layer was washed with water (100 mL)
and brine, dried (Na SO ), filtered, and concentrated. The crude
(ddd, J = 14.8, 8.0, 3.6 Hz, 1H). 13C NMR (101 MHz, CDCl ) δ
3
159.3, 140.8, 138.1, 130.2, 129.6, 117.3, 114.1, 113.9, 77.7, 70.2, 69.8,
+
55.4, 41.8; m/z (ESI+) found [M + NH ] 266.1760, C H O
2
4
4
15 20
3
requires 266.1756; [α]2 +139 (c 6.4, DCM).
3.6
D
extract was purified by silica gel chromatography (10% EtOAc/
hexanes) to afford the product as yellow oil (5.4 g, 96%): R = 0.73
General Procedure for the Synthesis of Compounds 6a−d. A
solution of starting diene (7a−7d) in DCM (0.02 M) was purged with
argon for 5 min, and Grubbs I catalyst (3 mol %) was added to it
under argon. The reaction mixture was stirred for 1 h at 50 °C and
quenched with DMSO (1 mL). The solution was stirred under air for
5 min and concentrated. The solvent was evaporated, and the crude
reaction mixture was purified by silica gel flash column chromatog-
raphy to obtain the product (6a−6d).
f
−1 1
(
20% EtOAc/hexanes); IR (neat) 3423 cm ; H NMR (400 MHz,
CDCl ) δ 5.94 (ddd, J = 17.1, 10.5, 5.9, 1H), 5.83 (ddd, J = 17.1, 10.4,
3
5
1
1
1
.6, 1H), 5.26 (ddd, J = 12.0, 1.5, 1.5 Hz, 1H), 5.22 (ddd, J = 11.8, 1.4,
.4 Hz, 1H), 5.14 (ddd, J = 10.5, 1.4, 1.4 Hz, 1H), 5.09 (ddd, J = 10.5,
.5, 1.5 Hz, 1H), 4.62−4.56 (m, 1H), 4.47−4.37 (m, 1H), 3.59 (bs,
H), 1.87 (ddd, J = 14.0, 9.6, 4.4 Hz, 1H), 1.68 (ddd, J = 14.4, 4.4, 2.8
13
Hz, 1H), 1.03−1.10 (m, 21H); C NMR (100.6 MHz, CDCl ) δ
3
1
40.9, 140.0, 114.9, 114.0, 73.2, 69.6, 43.2, 18.01, 17.99, 12.2; m/z
(1R,4R)-4-((Triisopropylsilyl)oxy)cyclopent-2-enol (6a). Following
the general procedure above, diene 7a (5.00 g, 17.6 mmol) provided
+
(
ESI+) found [M + H] 285.2253, C H O Si requires 285.2255;
16
32
24.0
2
2
3.6
[α] −5.4 (c 1.0, DCM); (3S,4S)-7a [α]D +5.7 (c 1.5, DCM).
cyclopentenol 6a (4.14 g, 92%) as a colorless oil: R = 0.41 (20%
D
f
−1 1
(
3R,5R)-5-((tert-Butyldimethylsilyl)oxy)hepta-1,6-dien-3-ol (7b).
EtOAc/hexanes); IR (neat) 3322 cm ; H NMR (400 MHz, CDCl )
3
To a stirred solution of (R,R)-4 (150 mg, 1.17 mmol) and tert-
butyldimethylsilyltrifluoromethane sulfonate (1.17 mmol, 0.269 mL)
in THF (20 mL) at −78 °C was added 2,6-lutidine (1.36 mL, 11.7
mmol) dropwise via syringe. The solution was allowed to stir for 2 h at
δ 6.04−5.80 (m, 2H), 5.24−5.06 (m, 1H), 4.98 (d, J = 1.9 Hz, 1H),
13
2.24−1.96 (m, 3H), 1.17−0.91 (m, 22H); C NMR (101 MHz,
CDCl ) δ 138.5, 135.5, 76.6, 76.2, 44.8, 18.1, 18.0, 12.2; m/z (APCI+)
3
+
23.4
D
found [M + H] 243.1780, C H O Si requires 243.1783; [α]
13
26
3.7
2
2
−
78 °C. The reaction was quenched with saturated aqueous NH Cl
+108 (c 2.2, DCM); (1S,4S)-6a [α]D −103.5 (c 3.0, DCM).
(1R,4R)-4-((tert-Butyldimethylsilyl)oxy)cyclopent-2-enol (6b). Fol-
lowing the general procedure above, diene 7b (200 mg, 17.6 mmol)
4
(
20 mL) and extracted with ethyl acetate (3 × 30 mL). The combined
organic phase was washed with brine, dried (Na SO ), filtered, and
2
4
concentrated. The crude product was purified by silica gel
chromatography (10% EtOAc/hexanes) to afford the desired product
provided cyclopentenol 6b (156 mg, 88%) as a colorless oil: R = 0.44
f
1
(20% EtOAc/hexanes); IR (neat) 3327; H NMR (400 MHz, CDCl )
3
as colorless oil (260 mg, 92%): R = 0.62 (20% EtOAc/hexanes); IR
δ 5.95−5.90 (m, 2H), 5.08−5.05 (m, 1H), 5.03−4.97 (m, 1H), 2.08−
f
−1
1
13
(
2
neat) 3419 cm ; H NMR (400 MHz, CDCl ) δ 5.91−5.81 (m,
H), 5.26 (dt, J = 4.0, 1.6 Hz, 1H), 5.22 (dt, J = 3.6 Hz, 1H), 5.09
1.97 (m, 2H), 1.74 (s, 1H), 0.88 (s, 9H), 0.07 (s, 6H). C NMR (101
3
MHz, CDCl ) δ 138.5, 135.6, 76.7, 76.3, 44.6, 26.0, 18.3, −4.5; m/z
3
+
(
ddt, J = 20.0, 10.4, 1.6 Hz, 2H), 4.51−4.47 (m, 1H), 4.41−4.36 (m,
(APCI+) found [M + H] 243.1780, C H O Si requires 243.1783;
13
26
2
[α]2 +89 (c 5.4, MeOH) [lit [α]D +81 (c 0.059, MeOH)].
3.6
D
5
20
1
(
H), 3.26 (d, J = 2.8 Hz, 1H), 1.77−1.65 (m, 2H), 0.91 (s, 9H), 0.08
d, J = 12.0 Hz, 6H). 13C NMR (101 MHz, CDCl ) δ 141.0, 140.2,
(1R,4R)-4-Hydroxycyclopent-2-en-1-yl Acetate (6c). Following the
general procedure above, diene 7c (200 mg, 1.17 mmol) provided
cyclopentenol 6c (147 mg, 88%) as a colorless oil: IR (neat) 3374,
3
+
1
2
14.7, 114.0, 72.4, 69.7, 43.3, 25.9, 18.2; m/z (ESI+) found [M + H]
43.1780, C H O Si requires 243.1783; [α] −11 (c 8.9, DCM).
2
3.4
13
26
2
D
−
1 1
(3R,5R)-5-Hydroxyhepta-1,6-dien-3-yl acetate (7c). To a stirred
1723 cm ; H NMR (400 MHz, CDCl ) δ 6.12−6.06 (m, 1H), 6.01−
3
solution of (R,R)-4 (200 mg, 1.56 mmol) in acetonitrile (15 mL) were
added triethyl orthoacetate (0.43 mL, 2.34 mmol) and p-toluene-
sulfonic acid (20 mg). The reaction mixture was stirred at rt for 1 h,
and a mixture of hydrochloric acid in methanol (0.2 mL of HCl in 1
mL of MeOH) was added to it. The stirring was continued for another
5.95 (m, 1H), 5.81−5.74 (m, 1H), 5.04−4.97 (m, 1H), 2.49 (br s,
1H), 2.17 (ddd, J = 14.8, 6.8, 2.8 Hz, 1H), 2.06 (ddd, J = 14.8, 7.2, 3.6
Hz, 1H), 2.00 (s, 3H). 13C NMR (101 MHz, CDCl ) δ 171.2, 139.9,
3
+
132.8, 79.1, 75.8, 40.6, 21.2; m/z (APCI+) found [M + H] 243.1780,
2
3.2
5
20
C H O Si requires 243.1783; [α] +227 (c 4.9, MeOH) [lit [α]D
13
26
2
D
3
h at rt. The reaction was quenched with saturated aqueous NaHCO3
+229 (c 0.027, MeOH)].
solution (10 mL) and was extracted with ethyl acetate (20 mL × 3).
(1R,4R)-4-((4-Methoxybenzyl)oxy)cyclopent-2-enol (6d). Follow-
ing the general procedure above, diene 7d (200 mg, 0.81 mmol)
The combined organic layer was washed with brine, dried (Na SO ),
2
4
and concentrated. Purification via flash column chromatography
provided cyclopentenol 6d (159 mg, 89%) as a colorless oil: R = 0.40
(30% EtOAc/hexanes); IR (neat) 3364 cm ; H NMR (400 MHz,
f
−1 1
provided the desired product as colorless oil (213 mg, 82%): R =
f
−1
1
0
.52 (20% EtOAc/hexanes); IR (neat) 3426 cm ; H NMR (400
CDCl ) δ 7.31−7.26 (m, 2H), 6.93−6.87 (m, 2H), 6.12−6.03 (m,
3
MHz, CDCl ) δ 5.87−5.75 (m, 2H), 5.48−5.42 (m, 1H), 5.23 (d, J =
2H), 5.08−5.00 (m, 1H), 4.85−4.78 (m, 1H), 4.50 (d, J = 11.2 Hz,
3
1
1
7.2 Hz, 2H), 5.10 (dd, J = 23.2, 10.4 Hz, 2H), 4.08 (bs, 1H), 2.73 (s,
H), 2.06 (s, 3H), 1.85−1.64 (m, 2H); C NMR (101 MHz, CDCl3)
1H), 4.45 (d, J = 11.2 Hz, 1H), 3.82 (s, 3H), 2.22 (ddd, J = 14.4, 6.8,
13
13
3.2 Hz, 1H), 2.00 (ddd, J = 14.4, 6.8, 2.8 Hz, 1H), 1.85 (bs, 1H);
C
δ 171.1, 140.2, 136.3, 116.6, 114.8, 71.8, 68.7, 42.0, 21.2; m/z (ESI+)
found [M + H] 171.1017, C H O requires 171.1021; [α] +16 (c
NMR (101 MHz, CDCl ) δ 159.3, 137.9, 135.1, 130.6, 129.5, 113.9,
3
+
23.6
D
+
82.9, 70.9, 55.4, 41.1; m/z (APCI+) found [M + H] 243.1780,
C H O Si requires 243.1783; [α] +139 (c 6.4, DCM).
13 26 2 D
9
14
3
23.4
1
2.6, DCM).
3R,5R)-5-((4-Methoxybenzyl)oxy)hepta-1,6-dien-3-ol (7d). To a
00 mL round-bottom flask containing sodium hydride (83 mg of 50%
(
General Procedure for the Synthesis of Compounds 1a−d.
1
To a stirred solution of starting cyclopentenol (6a−6d) in DCM (0.1
M) was added pyridinium chlorochromate (1.5 equiv) at 0 °C. The
reaction mixture was stirred at rt for 6 h followed by filtration over
Celite. The Celite bed was washed with diethyl ether. The combined
filtrate was concentrated and purified by silica gel flash column
chromatography to afford the desired enone (1a−1d).
dispersion, 1.72 mmol, prewashed with hexane) under argon was
transferred a solution of (3R,5R)-hepta-1,6-diene-3,5-diol (200 mg,
1.56 mmol) in THF (20 mL) via syringe at 0 °C. The solution was
stirred for 30 min at rt and again cooled to 0 °C by keeping in an ice−
water bath. A solution of 4-methoxybenzyl chloride (366 mg in 2 mL
of THF, 2.34 mmol) was added via syringe, and the reaction mixture
was stirred at rt for overnight. The reaction was quenched with
saturated aqueous ammonium chloride solution (10 mL) and was
extracted with EtOAc (20 mL × 3). The combined organic layer was
washed with brine, dried (Na SO ), and concentrated. Purification via
(R)-4-((Triisopropylsilyl)oxy)cyclopent-2-enone (1a). Following
above general procedure, cyclopentenol 6a (2.00 g, 7.81 mmol)
provided cyclopentenone 1a (1.86 g, 94%) as a colorless oil: R = 0.30
f
−1 1
(10% EtOAc/hexanes); IR (neat) 1725 cm ; H NMR (400 MHz,
CDCl ) δ 7.49 (dd, J = 5.7, 2.3 Hz, 1H), 6.16 (dd, J = 5.7, 1.2 Hz, 1H),
2
4
3
flash column chromatography provided the desired product as
2.73 (dd, J = 18.1, 5.9 Hz, 1 H), 2.28 (dd, J = 18.1, 2.2 Hz, 1H), 1.21−
colorless oil (236 mg, 66%): R = 0.55 (20% EtOAc/hexanes); IR
0.98 (m, 3H), 1.06 (d, J = 5.4 Hz, 18H); 13C NMR (101 MHz,
f
D
dx.doi.org/10.1021/jo402539p | J. Org. Chem. XXXX, XXX, XXX−XXX