L. W. K. Moodie, D. S. Larsen
FULL PAPER
5-tert-Butyldimethylsilyloxy-5-methylocten-7-yn-3-ol (13):[14]
A
73.04, 67.22, 46.49, 38.31, 30.90, 25.84, 18.23, –2.04, –2.44 ppm.
solution of the aldehyde (418 mg, 1.7 mmol) in toluene (11.2 mL)
was stirred under argon at –78 °C and then treated with freshly
IR (ATR): ν = 3308, 2927, 2855, 2362, 1606, 1250, 1090, 1027, 990,
˜
832, 805 cm–1. HRMS (ESI): calcd. for C15H28NaO2Si [M + Na]+
prepared vinylmagnesium bromide in THF (7.2 mL, 4.2 mmol). 291.1751; found 291.1725. C15H28O2Si (268.47): calcd. C 67.11, H
The reaction was warmed to room temperature and then stirred for
2 h. After quenching with saturated NH4Cl (5 mL), the aqueous
layer was extracted with EtOAc (3ϫ 10 mL). The combined or-
ganic extracts were washed with brine (10 mL) and dried with
MgSO4. The solvent was removed in vacuo, and the compound was
purified by column chromatography (Et2O/petroleum ether, 1:9) to
provide the title compounds (442 mg, 95%, inseparable mixture of
10.51; found C 67.39, H 10.68.
Cycloadducts (–)-22 and (–)-21: A solution of N-phenylmaleimide
(9.2 mg, 0.053 mmol) and diene 9a (15 mg, 0.056 mg) in toluene
(250 μL) was stirred for 40 h under an inert atmosphere. The sol-
vent was removed in vacuo. The resulting residue was purified by
column chromatography (EtOAc/petroleum ether, 1:9–1:1) and
then recrystallized (CH2Cl2 and petroleum ether) to yield 22
(8.5 mg, 34%) as a white solid; m.p. 147.1 °C. The column was then
flushed with EtOAc, and the resulting eluent was removed under
reduced pressure to yield 21 (13.2 mg, 53%) as an opaque gum.
diastereomers, 1.2:1) as a colorless oil. IR (ATR): ν = 3474, 3312,
˜
2954, 2929, 2119, 1253, 1103, 990, 831, 772, 628 cm–1. HRMS
(ESI): calcd. for C15H28NaO2Si [M + Na]+ 291.1751; found
291.1741. C15H28O2Si (268.47): calcd. C 67.11, H 10.51; found C
67.21, H 10.58. Data for diastereomer 1: 1H NMR (500 MHz,
1
Data for 22: [α]2D2 = –129 (c = 0.22, CHCl3). H NMR (500 MHz,
3
CDCl3, 25 °C): δ = 7.45 (t, JH,H = 7.6 Hz, 1 H), 7.37–7.32 (m, 4
3
CDCl3, 25 °C): δ = 5.91–5.81 (m, 1 H), 5.28 (dt, JH,H = 17.1,
3
3
H), 5.75 (t, JH,H = 3.7 Hz, 1 H), 4.20 (dq, JH,H = 10.5, 2.9 Hz, 1
3
1.5 Hz, 1 H), 5.08 (ddt, JH,H = 10.4, 3.0, 1.5 Hz, 1 H), 4.52–4.44
3
3
H), 3.75 (d, JH,H = 10.6 Hz, 1 H), 3.36 (t, JH,H = 9.5 Hz, 1 H),
3
3
(m, 1 H), 3.48 (t, JH,H = 1.7 Hz, 1 H), 2.53 (dd, JH,H = 16.4,
3.19 (ddd, 3JH,H = 10.6, 9.5, 2.8 Hz, 1 H), 2.82 (d, 3JH,H = 19.1 Hz,
3
3
2.6 Hz, 1 H), 2.43 (dd, JH,H = 16.4, 2.7 Hz, 1 H), 2.04 (t, JH,H
=
3
3
1 H), 2.64 (d, JH,H = 9.3 Hz, 1 H), 2.48 (ddq, JH,H = 19.2, 10.6,
2.7 Hz, 1 H), 1.90 (dd, 3JH,H = 14.6, 10.1 Hz, 1 H), 1.76 (dd, 3JH,H
= 14.6, 2.1 Hz, 1 H), 1.46 (s, 3 H), 0.89 (s, 9 H), 0.17 (s, 6 H) ppm.
13C NMR (125 MHz, CDCl3, 25 °C): δ = 141.22, 114.01, 81.13,
76.74, 71.29, 69.96, 47.41, 34.33, 26.73, 25.95, 18.21, –1.86 ppm.
3.3 Hz, 1 H), 2.42 (dd, 3JH,H = 13.0, 2.9 Hz, 1 H), 2.13 (d, JH,H
=
3
3
3
13.1 Hz, 1 H), 2.00 (dt, JH,H = 14.6, 3.0 Hz, 1 H), 1.59 (dd, JH,H
= 14.5, 3.1 Hz, 1 H), 1.32 (s, 3 H), 0.84 (s, 9 H), 0.16 (s, 3 H), 0.12
(s, 3 H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 178.91,
178.20, 132.72, 130.02, 129.17, 128.44, 127.09, 123.45, 77.47, 69.82,
50.34, 45.07, 40.98, 39.96, 36.54, 30.75, 26.11, 20.71, 18.19, –1.57,
1
Data for diastereomer 2: H NMR (500 MHz, CDCl3, 25 °C): δ =
3
5.91–5.81 (m, 1 H), 5.28 (dt, JH,H = 17.1, 1.5 Hz, 1 H), 5.08 (ddt,
3
3JH,H = 10.4, 3.0, 1.5 Hz, 1 H), 4.52–4.44 (m, 1 H), 3.70 (t, JH,H
–1.61 ppm. IR (ATR): ν = 2955, 2929, 1702, 1383, 1252, 1193,
˜
3
= 1.7 Hz, 1 H), 2.66 (dd, JH,H = 16.5, 2.6 Hz, 1 H), 2.49 (ddd,
1145, 1093 cm–1. HRMS (ESI): calcd. for C25H35NNaO4Si [M +
3
3JH,H = 16.5, 2.7, 1.1 Hz, 1 H), 2.02 (t, JH,H = 2.7 Hz, 1 H), 1.93
Na]+ 464.2228; found 464.2197. Data for 21: [α]2D2 = –48 (c = 0.5,
3
3
(dd, JH,H = 14.6, 2.2 Hz, 1 H), 1.69 (ddd, JH,H = 14.6, 10.4,
1.0 Hz, 1 H), 1.44 (s, 3 H), 0.88 (s, 9 H), 0.18 (s, 6 H) ppm. 13C
NMR (125 MHz, CDCl3, 25 °C): δ = 141.14, 114.01, 80.99, 77.28,
71.27, 70.07, 47.11, 31.50, 28.90, 25.95, 18.13, –1.86 ppm.
1
3
CHCl3). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.46 (t, JH,H
=
7.6 Hz, 2 H), 7.39 (t, 3JH,H = 7.4 Hz, 1 H), 7.21 (d, 3JH,H = 8.2 Hz,
2 H), 5.65 (s, 1 H), 4.22 (td, 3JH,H = 9.9, 5.6 Hz, 1 H), 3.65 (t, 3JH,H
3
= 8.3 Hz, 1 H), 3.24 (ddd, JH,H = 8.5, 7.0, 4.3 Hz, 1 H), 2.62 (dt,
3JH,H = 16.0, 4.9 Hz, 1 H), 2.50 (t, JH,H = 8.9 Hz, 1 H), 2.32 (d,
3
3-tert-Butyldimethylsilyloxy-5-ethenyl-3-methylcyclohex-5-en-1-ol
[(+)-9a and (+)-9b]: Grubbs first generation catalyst (35 mg
0.04 mmol) was added to a solution of enyne 13 (115 mg,
0.40 mmol) in CH2Cl2 (9.5 mL) under argon. After 24 h, the 1H
NMR spectrum of an aliquot from the reaction mixture revealed
complete conversion. DMSO (150 μL, 2.1 mmol) was added, and
the reaction mixture was stirred for an additional 16 h. The solvent
was removed under reduced pressure, and the residue was subjected
to column chromatography (EtOAc/petroleum ether, 1:15) to afford
9a (56 mg, 58%) and the slower eluting diastereomer 9b (35 mg,
30%). Data for 9a: [α]2D2 = +74.06 (c = 0.5, CHCl3). 1H NMR
3JH,H = 16.0 Hz, 1 H), 2.24 (d, JH,H = 14.4 Hz, 1 H), 2.21–2.13
3
3
(m, 2 H), 1.81 (dd, JH,H = 13.5, 10.1 Hz, 1 H), 1.26 (s, 3 H), 0.83
(s, 9 H), 0.10 (s, 3 H), 0.07 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 178.77, 178.49, 137.47, 131.80, 129.33, 128.90,
126.60, 120.91, 73.20, 67.94, 48.00, 46.06, 43.43, 41.32, 40.03,
30.11, 25.87, 24.76, 18.07, –1.84, –1.95 ppm. IR (ATR): ν = 2924,
˜
2853, 1699, 1499, 1378, 1252, 1183, 1139, 1037 cm–1. HRMS (ESI):
calcd. for C25H35NNaO4Si [M + Na]+ 464.2228; found 464.2198.
Lactonization of (–)-22: para-Toluenesulfonic acid (approximately
1 mg) was added to a stirred solution of 22 (3.6 mg, 0.008 mmol)
in MeOH (1.0 mL). After 4 h, TLC indicated the consumption of
the starting material, and the solvent was removed under reduced
pressure. The product was purified by column chromatography
(EtOAc) to afford 24 (2.2 mg, 82%). 1H NMR (500 MHz, [D6]acet-
3
(500 MHz, CDCl3, 25 °C): δ = 6.41 (dd, JH,H = 17.6, 10.8 Hz, 1
3
3
H), 5.91 (d, JH,H = 3.5 Hz, 1 H), 5.17 (d, JH,H = 17.6 Hz, 1 H),
3
3
5.05 (d, JH,H = 10.8 Hz, 1 H), 4.18 (br. s, 1 H), 3.34 (d, JH,H
9.7 Hz, 1 H), 2.47 (d, JH,H = 18.1 Hz, 1 H), 2.10–2.05 (m, 1 H),
=
3
3
2.07–2.02 (m, 1 H), 1.73 (dd, JH,H = 13.9, 5.3 Hz, 1 H), 1.36 (s, 3
3
one, 25 °C): δ = 9.39 (s, 1 H), 7.65 (dd, JH,H = 8.7, 1.2 Hz, 2 H),
H), 0.83 (s, 9 H), 0.14 (s, 3 H), 0.04 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 139.47, 134.27, 130.11, 112.76,
73.37, 65.74, 44.24, 38.01, 30.29, 25.88, 18.06, –1.96, –2.34 ppm.
3
3
7.29 (dd, JH,H = 8.5, 7.5 Hz, 2 H), 7.04 (tt, JH,H = 7.6, 1.1 Hz, 1
3
3
H), 5.77 (dq, JH,H = 4.0, 2.0 Hz, 1 H), 4.83 (td, JH,H = 4.2,
1.9 Hz, 1 H), 3.78 (dd, 3JH,H = 6.0, 3.2 Hz, 1 H), 3.16 (s, 1 H), 2.93
IR (ATR): ν = 3379, 2927, 2364, 1606, 1253, 1125, 1096 cm–1
.
˜
(ddd, 3JH,H = 11.9, 6.1, 3.3 Hz, 1 H), 2.52 (dq, 3JH,H = 11.9, 2.6 Hz,
HRMS (ESI): calcd. for C15H28NaO2Si [M + Na]+ 291.1751; found
291.1745. C15H28O2Si (268.47): calcd. C 67.11, H 10.51; found C
3
1 H), 2.49–2.41 (m, 1 H), 2.30–2.25 (m, 1 H), 2.20 (dt, JH,H
=
3
15.8, 2.3 Hz, 1 H), 2.19 (dd, JH,H = 13.3, 2.5 Hz, 1 H), 1.91 (dd,
3JH,H = 16.2, 4.0 Hz, 1 H), 1.21 (s, 3 H) ppm. 13C NMR (125 MHz,
[D6]acetone, 25 °C): δ = 177.33, 171.18, 140.40, 131.52, 129.44,
127.40, 124.12, 120.45, 80.63, 70.59, 47.01, 44.41, 42.35, 40.93,
39.34, 30.55, 25.38 ppm. HRMS (ESI): calcd. for C19H21NNaO4
[M + Na]+ 350.1363; found 350.1364.
67.31, H 10.58. Data for 9b: [α]2D2 = +33.83 (c = 0.5, CHCl3). H
1
3
NMR (500 MHz, CDCl3, 25 °C): δ = 6.39 (dd, JH,H = 17.5,
10.8 Hz, 1 H), 5.76 (s, 1 H), 5.14 (d, JH,H = 17.6 Hz, 1 H), 5.02
3
3
3
(d, JH,H = 10.7 Hz, 1 H), 4.59–4.47 (m, 1 H), 2.30 (d, JH,H
=
17.3 Hz, 1 H), 2.18 (dddd, 3JH,H = 12.3, 6.0, 2.1, 1.2 Hz, 1 H), 2.10
3
(dt, JH,H = 17.3, 2.5 Hz, 1 H), 1.38–1.32 (m, 1 H), 1.36 (s, 3 H),
0.79 (s, 9 H), 0.08 (s, 3 H), –0.01 (s, 3 H) ppm. 13C NMR Lactone (–)-26: N-Phenylmaleimide (9.2 mg, 0.053 mmol) and (+)-
(125 MHz, CDCl3, 25 °C): δ = 139.25, 135.09, 131.28, 112.54, 9b (14.2 mg, 0.053 mg) were dissolved in toluene (300 μL), and the
1690
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1684–1694