The Journal of Organic Chemistry
NOTE
(m, 2H), 2.41 (s, 1H), 2.13ꢀ1.01 (m, 1H), 1.82ꢀ1.74 (m, 2H), 1.68 (s,
3H), 1.58ꢀ1.48 (m, 3H), 1.43ꢀ1.32 (m, 2H), 1.25ꢀ1.16 (m, 1H),
1.02ꢀ0.66 (m, 5H) ppm. 13C NMR (75 MHz, CDCl3; major isomer): δ
144.8 (s), 108.9 (t), 84.1 (s), 73.1 (d), 72.6 (s), 42.5 (t), 28.4 (d), 26.4
(t), 23.0 (d), 22.8 (t), 20.9 (q), 14.0 (q), 8.2 (t) ppm. HRMS (ESI): m/z
calcd for C13H20O (M þ H)þ 193.1592, found 193.1593.
Method B: General Experimental Procedure for the Pre-
paration of Compounds 6aꢀf. A 0.25 M Au(I) catalyst was
prepared as follows: in a flame-dried 50 mL flask, the Au catalyst (5
mmol) and Ag catalyst (5 mmol) or TfOH (as shown in Table 1) were
added to dry CH2ClCH2Cl (20 mL) under an argon atmosphere. To the
preprepared catalyst solution (10 mmol % or as specified in Table 1) was
added a solution of substrate 1 (2 mL, 0.34 M) in CH2ClCH2Cl. The
reaction mixture was stirred at room temperature or heated to 85 °C
(as specified in Table 1) until complete. The reaction was monitored
by GC-MS. After completion, the reaction mixture was loaded directly
onto a silica gel column and eluted with 100/1 hexanes/ethyl acetate
to afford the enol acetates 60, which were directly subjected to
methanolysis by adding a mixture of K2CO3 (2.0 equiv) and MeOH
(5 mL) at room temperature for 2 h. Dilute HCl (20 mL) was added,
and the mixture was extracted by MTBE (3 ꢁ 10 mL), dried (MgSO4),
and concentrated under reduced pressure. Ketones 6 and acetate 6f
were purified by flash chromatography or bulb-to-bulb distillation.
2,4-Dimethyl-4-vinylcyclohex-2-enone (6a). Colorless oil; 70%
Method A: General Procedure for the Synthesis of Cyclo-
propyl Propargyl Acetates 1aꢀe. A mixture consisting of cyclo-
propyl propargyl alcohol 14 (48.78 mmol), Ac2O (14.92 g, 146.3
mmol), Et3N (24.63 g, 243.9 mmol), and DMAP (0.30 g, 2.44 mmol)
was stirred overnight and quenched by the addition of H2O (100 mL).
The mixture was extracted with MTBE (3 ꢁ 50 mL). The combined
organic phases were washed with saturated aqueous NaHCO3, dried over
MgSO4, filtered, and concentrated under reduced pressure. The residue
was subjected to bulb-to-bulb distillation to furnish pure substrates 1aꢀd.
trans-2-[2-(1-Methylethenyl)cyclopropyl]but-3-yn-2-yl Acetate
(1a). Colorless oil; 90% yield. dr = 45:55. 1H NMR (300 MHz, CDCl3):
δ 4.85ꢀ4.62 (m, 2H), 2.52 (s, 1H), 2.04 (s, 3H), 1.84ꢀ1.66 (m, 6H),
1.63ꢀ1.55 (m, 1H), 1.46ꢀ1.38 (m, 1H), 1.12ꢀ0.76 (m, 2H) ppm. 13C
NMR (75 MHz, CDCl3; major isomer): δ 169.2 (s), 144.6 (s), 108.8 (t),
81.2 (s), 76.6 (s), 73.9 (d), 27.8 (d), 27.0 (q), 22.4 (d), 21.9 (q), 21.2
(q), 10.2 (t) ppm. HRMS (ESI): m/z calcd for C12H16O2 (M þ Na)þ
215.1048, found 215.1055.
1
yield. H NMR (300 MHz, CDCl3): δ 6.39 (s, 1H), 5.80 (dd, J =
10.5, 17.4 Hz, 1H), 5.10 (d, J = 10.5 Hz, 1H), 5.02 (d, J = 17.4 Hz, 1H),
2.49ꢀ2.34 (m, 2H), 1.93ꢀ1.89 (m, 2H), 1.80 (s, 3H), 1.22 (s, 3H) ppm.
13C NMR (75 MHz, CDCl3): δ 199.8 (s), 151.1 (d), 143.3 (d), 134.4
(s), 113.8 (t), 39.6 (s), 35.0 (t), 34.3 (t), 27.3 (q), 16.0 (q) ppm. HRMS
(ESI): m/z calcd for C10H14O (M þ Na)þ 173.0942, found 173.0936.
2-Ethyl-4-methyl-4-vinylcyclohex-2-enone (6b). Colorless oil. 1H
NMR (300 MHz, CDCl3): δ 6.33 (s, 1H), 5.81 (dd, J = 10.5, 17.4 Hz,
1H), 5.10 (d, J = 10.5 Hz, 1H), 5.02 (d, J = 17.4 Hz, 1H), 2.51ꢀ2.38 (m,
2H), 2.38ꢀ2.20 (m, 2H), 1.92ꢀ1.88 (m, 2H), 1.23 (s, 3H), 1.03 (t, J =
7.5 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3): δ 198.4 (s), 148.5 (d),
142.4 (d), 139.0 (s), 112.7 (t), 38.4 (s), 33.8 (t), 33.6 (t), 26.5 (q), 21.4
(t), 12.0 (q) ppm. HRMS (ESI): m/z calcd for C11H16O (M þ H)þ
165.1279, found 165.1286.
trans-3-[2-(1-Methylethenyl)cyclopropyl]pent-1-yn-3-yl Acetate
(1b). Colorless oil; 92% yield. dr = 24:76. 1H NMR (300 MHz, CDCl3):
δ 4.89ꢀ4.66 (m, 2H), 2.53 (s, 1H), 2.31ꢀ1.96 (m, 5H), 1.85ꢀ1.75 (m,
1H), 1.74ꢀ1.63 (m, 3H), 1.63ꢀ1.57 (m, 1H), 1.47ꢀ1.40 (m, 1H),
1.17ꢀ1.09 (m, 1H), 1.04 (t, J = 7.4 Hz, 3H), 0.90ꢀ0.78 (m, 1H) ppm.
13C NMR (75 MHz, CDCl3; major isomer): δ 169.2 (s), 144.6 (s),
109.2 (t), 81.3 (s), 79.9 (s), 75.1 (d), 33.1 (t), 25.1 (d), 23.1 (d), 21.9
(q), 20.7 (q), 10.1 (t), 8.5 (q) ppm. HRMS (ESI): m/z calcd for
C13H18O2 (M þ H)þ 207.1385, found 207.1366.
1
trans-3-[2-(1-Methylethenyl)cyclopropyl]hex-1-yn-3-yl Acetate
(1c). Colorless oil; 89% yield. dr = 35:65. 1H NMR (300 MHz, CDCl3):
δ 4.71 (s, 1H), 4.68 (s, 1H), 2.52 (s, 1H), 2.22ꢀ1.68 (m, 5H),
1.66ꢀ1.40 (m, 7H), 1.16ꢀ1.10 (m, 1H), 0.97 ꢀ0.77 (m, 4H) ppm.
13C NMR (75 MHz, CDCl3; major isomer): δ 169.2 (s), 144.6 (s),
109.2 (t), 80.8 (s), 80.1 (s), 75.0 (d), 42.1 (t), 25.5 (d), 23.1 (d), 22.0
(q), 20.7 (q), 17.5 (t), 14.0 (q), 10.2 (t) ppm. HRMS (ESI): m/z calcd
for C14H20O2 (M þ Na)þ 243.1361, found 243.1356.
4-Methyl-2-propyl-4-vinylcyclohex-2-enone (6c). Colorless oil. H
NMR (300 MHz, CDCl3): δ 6.33 (s, 1H), 5.84 (dd, J = 10.5, 17.4 Hz,
1H), 5.10 (dd, J = 0.9, 10.5 Hz, 1H), 5.02 (dd, J = 0.9, 17.4 Hz, 1H),
2.52ꢀ2.31 (m, 2H), 2.20ꢀ2.14 (m, 2H), 1.92ꢀ1.87 (m, 2H),
1.47ꢀ1.40 (q, J = 7.5 Hz, 2H), 1.22 (s, 3H), 0.90 (t, J = 7.3 Hz, 3H)
ppm. 13C NMR (75 MHz, CDCl3): δ 199.4 (s), 150.6 (d), 143.4 (d),
138.4 (s), 113.8 (t), 39.5 (s), 34.9 (t), 34.6 (t), 31.5(t), 27.5 (q), 21.8 (t),
13.8 (q) ppm. HRMS (ESI): m/z calcd for C12H18O (M þ Na)þ
201.1255, found 201.1254.
trans-3-[2-(1-Methylethenyl)cyclopropyl]hept-1-yn-3-yl Acetate
(1d). Colorless oil; 92% yield. dr = 32:68. 1H NMR (300 MHz, CDCl3):
δ 4.79ꢀ4.46 (m, 2H), 2.46 (s, 1H), 2.30ꢀ2.05 (m, 2H), 1.96ꢀ1.90 (m,
3H), 1.75ꢀ1.16 (m, 9H), 1.09ꢀ1.02 (m, 1H), 0.97ꢀ0.79 (m, 3H),
0.78ꢀ0.72 (m, 1H) ppm. 13C NMR (75 MHz, CDCl3; major isomer): δ
169.1 (s), 144.5 (s), 109.1 (t), 80.8 (s), 80.1 (s), 75.0 (d), 39.7 (t), 26.2
(t), 25.5 (d), 23.1 (d), 22.6 (t), 21.9 (q), 20.7 (q), 13.9 (q), 10.1 (t) ppm.
HRMS (ESI): m/z calcd for C15H22O2 (M þ H)þ 235.1698, found
235.1679.
6-Butyl-4-methyl-4-vinylcyclohexa-1,5-dienyl Acetate (6d0). This
compound was prepared according to the general procedure without
1
applying the in situ methanolysis. Colorless oil; 90% yield. H NMR
(300 MHz, CDCl3): δ 5.87 (dd, J = 10.5, 17.4 Hz, 1H), 5.32ꢀ5.30 (m,
2H), 5.07 (dd, J = 1.3, 17.4 Hz, 1H), 4.97 (dd, J = 1.3, 10.5 Hz, 1H), 2.29
(dd, J = 5.0, 9.2 Hz, 2H), 2.16 (s, 3H), 1.96 (t, J = 6.4 Hz, 2H), 1.43ꢀ1.27
(m, 4H), 1.14 (s, 3H), 0.90 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (75 MHz,
CDCl3): δ 169.5 (s), 146.5 (s), 144.7 (d), 132.6 (s), 132.1 (d), 111.3
(d), 111.3 (t), 37.6 (s), 35.1 (t), 30.6 (t), 30.4 (t), 25.3 (q), 22.4 (t), 20.8
(q), 13.9 (q) ppm. HRMS (ESI): m/z calcd for C15H22O2 (M þ Na)þ
257.1518, found 257.1517.
trans-1-Deuterium-3-[2-(1-methylethenyl)cyclopropyl]hept-1-yn-
3-yl Acetate (1e). To a solution of 1d (150 mg, 0.64 mmol) in dry THF
(1 mL) at ꢀ78 °C was added dropwise a 1.6 mol/L solution of n-BuLi in
hexanes (0.5 mL, 0.72 mmol). The reaction mixture was stirred for 1 h at
the same temperature and quenched by the addition of D2O (5 mL).
The mixture was extracted with Et2O (3 ꢁ 2 mL). The organic phases
were dried over MgSO4 and concentrated under reduced pressure.
Product 1e was purified by bulb-to-bulb distillation. Colorless oil; 93%
yield. D incorporation: 68%. 1H NMR (300 MHz, CDCl3): δ 4.79ꢀ4.63
(m, 2H), 2.30ꢀ1.98 (m, 2H), 2.05ꢀ2.01 (m, 3H), 1.79ꢀ1.28 (m, 9H),
0.98ꢀ0.73 (m, 5H) ppm. 13C NMR (75 MHz, CDCl3; major isomer): δ
169.3 (s), 145.1 (s), 108.7 (t), 81.1 (s), 80.8 (s), 75.0 (d), 39.7 (t), 26.3
(t), 25.6 (d), 22.6 (d), 22.0 (t), 21.2 (q), 20.8 (q), 14.0 (q), 10.2 (t) ppm.
HRMS (ESI): m/z calcd for C15H21DO2 (M þ Na)þ 258.1580, found
258.1588.
2-Butyl-4-methyl-4-vinylcyclohex-2-enone (6d). Colorless oil. 1H
NMR (300 MHz, CDCl3): δ 6.33 (s, 1 H), 5.80 (dd, J = 10.5, 17.4 Hz,
1H), 5.10 (d, J = 10.5 Hz, 1H), 5.02 (d, J = 17.4 Hz, 1H), 2.57ꢀ2.31 (m,
2H), 2.29ꢀ2.12 (m, 2H), 2.02ꢀ1.83 (m, 2H), 1.58ꢀ1.14 (m, 7H),
1.07ꢀ0.76 (m, 3H) ppm. 13C NMR (75 MHz, CDCl3): δ 199.4 (s),
150.4 (d), 143.4 (d), 138.6 (s), 113.7 (t), 39.5 (s), 34.9 (t), 34.6 (t), 30.9
(t), 29.2 (t), 27.5 (q), 22.5 (t), 13.9 (q) ppm. HRMS (ESI): m/z calcd
for C13H20O (M þ Na)þ 215.1412, found 215.1412.
2-Butyl-6-deuterium-4-methyl-4-vinylcyclohex-2-enone (6e). Col-
orless oil. D incorporation: 68%. 1H NMR (300 MHz, CDCl3): δ 6.33
(s, 1H), 5.80 (dd, J = 10.5, 17.4 Hz, 1H), 5.06 (d, J = 10.5 Hz, 1H), 5.96
(d, J = 17.4 Hz, 1H), 2.45ꢀ2.32 (m, 1H), 2.25ꢀ2.16 (m, 2H),
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dx.doi.org/10.1021/jo200416d |J. Org. Chem. 2011, 76, 5825–5831