Closser et al.
2.43 (s, 3H), 2.25 (m, 2H), 1.78 (m, 4H), 1.25 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 199.9, 143.7, 137.8, 136.8, 129.9, 127.2,
115.6, 98.4, 97.6, 81.1, 58.8, 43.0, 37.1, 31.8, 31.0, 30.3, 21.6.
2-But-3-enyl-1-(toluene-4-sulfonyl)-3-azepyne Dicobalt Hexa-
carbonyl Complex (40). A 25-mL flask containing cobalt-complexed
alkyne 39 (135 mg, 0.22 mmol, 1.0 equiv) was equipped with a
rubber septum and gas inlet needle. Dichloromethane (14 mL) was
added, the reaction flask was cooled at 0 °C, and boron trifluoride
diethyl etherate (27 µL, 0.22 mmol, 1.0 equiv) was added. The
reaction was stirred at 0 °C for 1.5 h then quenched by addition of
20 mL of saturated sodium bicarbonate. The organic layer was
removed and the aqueous layer was extracted twice with dichlo-
romethane. The combined organic layers were dried with magne-
sium sulfate and added to a sintered glass funnel filled with silica
gel and eluted with 5-20% diethyl ether in petroleum ether until
the solution ran clear and concentration afforded 93 mg (73%) of
rubber septum and gas inlet needle. Dimethylformamide (7 mL)
was added followed by Oxone (363 mg, 0.59 mmol, 1.0 equiv)
and the reaction was stirred at room temperature for 2 h. The
reaction mixture was added to a separatory funnel containing ethyl
acetate (30 mL) and 1.0 M hydrochloric acid (30 mL). The aqueous
layer was removed and extracted with 50 mL of ethyl acetate, and
the combined organic layers were washed with 1.0 M hydrochloric
acid (5 × 50 mL) and brine (50 mL), dried with magnesium sulfate,
filtered, and concentrated to yield 143 mg (108%) of the desired
carboxylic acid as a yellow oil that was used without further
purification: IR (neat) 3077, 2937, 2867, 2650, 2230, 1711, 1648,
cm-1; 1H NMR (400 MHz, CDCl3) δ 5.81 (ddt, J ) 17.2, 10.2, 6.6
Hz, 1H), 5.04 (dq, J ) 17.0, 1.8 Hz, 1H), 4.97 (dm, J ) 11.0 Hz,
1H), 3.92 (tt, J ) 6.6, 1.8 Hz, 1H), 3.38 (s, 3H), 2.94 (d, J ) 30.4
Hz, 3H), 2.38 (t, J ) 7.5 Hz, 2H), 2.26 (td, J ) 7.0, 1.9 Hz, 2H),
2.20 (m, 2H), 1.76 (m, 4H), 1.57 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 179.1, 137.9, 115.1, 85.9, 79.1, 70.8, 56.2, 35.0, 33.6,
29.5, 28.1, 23.9, 18.5; HRMS-FAB m/z [M - H]+ calcd for
C13H19O3 223.1334, found 223.1351.
8-Methoxydodec-11-en-6-ynoic Acid Dicobalt Hexacarbon-
yl Complex (61). According to the general procedure, combination
of the carboxylic acid resulting from oxidation of alcohol 24 (52
mg, 0.23 mmol, 1.0 equiv), dichloromethane (1 mL), and dicobalt
octacarbonyl (95 mg, 0.28 mmol, 1.2 equiv, then 31 mg, 0.09 mmol,
0.4 equiv) followed by direct addition to a 12 g silica gel column
and eluting with 15-100% diethyl ether in petroleum ether yielded
62 mg (52%) of 61 as a dark red oil: 1H NMR (400 MHz, CDCl3)
δ 10.8 (br s, 1H), 5.85 (m, 1H), 5.05 (m, 2H), 4.27 (m, 1H), 3.48
(s, 3H), 2.86 (br s, 2H), 2.26 (m, 2H), 1.79 (m, 6H), 1.28 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 200.1, 137.8, 115.5, 98.3, 81.1,
67.0, 58.8, 37.1, 33.7, 30.4, 22.4, 15.3, 14.2.
9,18-Dibut-3-enyl-1,10-dioxacyclooctadeca-7,16-diyne-2,11-di-
one Dicobalt Hexacarbonyl Complex (62). According to the
general procedure, combination of cobalt-complexed alkyne 61 (62
mg, 0.12 mmol, 1.0 equiv), dichloromethane (6 mL), and tetrafluo-
roboric acid (54% in diethyl ether, 17 µL, 0.12 mmol, 1.0 equiv)
at 0 °C for 1 h followed by aqueous workup and addition to a
sintered glass funnel filled with silica gel and eluting with 10%
diethyl ether in petroleum ether until the solution ran clear and
concentration afforded 10 mg (9%) of 62 as a dark red oil: 1H NMR
(400 MHz, CDCl3) δ 6.03 (m, 2H), 5.84 (m, 2H), 5.03 (m, 4H),
2.80 (m, 4H), 2.55-2.19 (m, 6H), 2.01-1.54 (m, 14H); 13C NMR
(100 MHz, CDCl3) δ 199.7, 172.5, 137.1, 125.6, 115.7, 99.3, 72.8,
35.8, 34.3, 33.3, 31.5, 30.2, 25.2.
1
40 as a dark red oil: H NMR (400 MHz, CDCl3) δ 7.71 (d, J )
8.4 Hz, 2H), 7.29 (d, J ) 8.1 Hz, 2H), 5.58 (m, 1H), 5.19 (t, J )
7.3 Hz, 1H), 4.91 (m, 2H), 4.05 (m, 1H), 3.71 (m, 1H), 3.26 (m,
1H), 2.97 (m, 1H), 2.79 (m, 1H), 2.41 (s, 3H), 2.04 (m, 2H), 1.90
(m, 1H), 1.78 (m, 1H), 1.64 (m, 1H), 1.34 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 199.9, 143.3, 138.8, 136.8, 129.7, 126.9, 115.7,
110.0, 98.6, 59.8, 45.3, 34.8, 34.3, 31.3, 30.1, 21.6.
1-Tosyl-1,2,3,4,6a,7,8,8a-octahydropentaleno[1,6-bc]azepin-
17
5(6H)-one (42). Cyclohexylamine: A 20-mL round-bottomed
flask containing Nicholas product 40 (93 mg, 0.16 mmol, 1.0 equiv)
was equipped with a rubber septum and gas inlet needle. 1,2-
Dimethoxyethane (5.5 mL) was added followed by cyclohexylamine
(27 µL, 0.24 mmol, 1.5 equiv). The rubber septum was replaced
with a reflux condenser and gas inlet adapter and the reaction was
heated at 60 °C for 3 h. The heat was removed and the reaction
was allowed to stir overnight. The reaction mixture was added to
a sintered glass funnel filled with Celite and washed with ethyl
acetate (50 mL) to yield 59 mg (113%) of a yellow oil. The crude
product was applied directly to a 6 g silica gel column and eluted
with 30% diethyl ether in petroleum ether to yield 51 mg (98%) of
1
42 as a colorless viscous oil: H NMR (400 MHz, CDCl3) δ 7.71
(d, J ) 8.4 Hz, 2H), 7.28 (d, J ) 8.1 Hz, 2H), 5.17 (t, J ) 8.4 Hz,
1H), 3.70 (dt, J ) 15.4, 3.7 Hz, 1H), 2.91 (m, 1H), 2.81 (m, 1H),
2.65 (dd, J ) 18.3, 6.6 Hz, 1H), 2.40 (s, 3H), 2.35-2.17 (m, 4H),
2.06 (dd, J ) 18.7, 2.2 Hz, 1H), 1.88 (m, 1H), 1.71 (m, 2H), 1.26
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 209.1, 178.7, 143.5, 137.8,
135.7, 129.9, 127.1, 57.9, 43.7, 42.6, 38.9, 31.6, 29.9, 26.6, 21.6,
18.8; HRMS-FAB m/z [M - H]+ calcd for C18H20NO3S 330.1164,
found 330.1153.
8-Methoxydodec-11-en-6-ynoic Acid.27,28 A 25-mL two-necked
flask equipped with a rubber septum and gas inlet adapter was
charged with Dess-Martin periodinane (520 mg, 1.23 mmol, 1.2
equiv) and dichloromethane (4.5 mL). A separate 25-mL pear flask
containing alcohol 24 (215 mg, 1.02 mmol, 1.0 equiv) in 1.0 mL
of dichloromethane was cannulated into the reaction flask followed
by a dichloromethane (0.5 mL) rinse. The reaction mixture was
stirred at room temperature for 1 h, diluted with 15 mL of diethyl
ether, transferred to an Erlenmeyer flask containing 15 mL of a
saturated sodium bicarbonate solution and 3 g of sodium thiosulfate,
and stirred for 5 min. The organic layer was washed with 50 mL
of saturated sodium bicarbonate and 50 mL of water, dried with
magnesium sulfate, filtered, and concentrated to yield 176 mg (83%)
of the desired aldehyde as a yellow oil: IR (neat) 3076, 2937, 2863,
2821, 2721, 2227, 1725, 1641 cm-1; 1H NMR (400 MHz, CDCl3)
9.77 (m, 1H), 5.81 (ddt, J ) 17.0, 10.4, 6.6 Hz, 1H), 5.03 (dd, J )
17.2, 1.5 Hz, 1H), 4.95 (dd, J ) 10.2, 1.1 Hz, 1H), 3.92 (tt, J )
6.6, 1.8 Hz, 1H), 3.38 (s, 3H), 2.46 (td, J ) 7.3, 1.6 Hz, 2H), 2.26
(td, J ) 7.0, 1.5 Hz, 2H), 2.18 (q, J ) 7.3 Hz, 2H), 1.76 (m, 4H),
1.56 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 202.3, 137.8, 115.0,
85.7, 79.2, 70.8, 56.2, 43.3, 35.0, 29.5, 28.1, 21.2, 18.5; HRMS-
FAB m/z [M - H]+ calcd for C13H19O2 207.1385, found 207.1404.
A 50-mL round-bottomed flask containing the previous prepared
aldehyde (123 mg, 0.59 mmol, 1.0 equiv) was equipped with a
Acknowledgment. We thank Research Corporation and Smith
College for generous financial support. M.M.Q. would like to thank
Pfizer for a summer undergraduate research fellowship. We thank
Amanda Freeman and Kate Whitesell for investigating the use of
chiral amine promoters in the Pauson-Khand reaction. We thank
the reviewers for helpful suggestions to improve the clarity and
overall quality of this manuscript. We thank Dr. Charles Amass
(Smith College) for assistance with NMR experiments, Dr. Mohini
Kulp (Smith College) and the Center for Proteomics for assistance
with MS experiments, and Dr. Stephen J. Eyles (University of
Massachusetts, Amherst) and the University of Massachusetts Mass
Spectrometry Facility, which is supported, in part, by the National
Science Foundation for assistance with HRMS experiments.
Supporting Information Available: General experimental
details, materials, references to compounds previously reported
in the literature, experimental procedures for all new compounds,
1
1D H NMR spectra for compounds 20-33, 39-47, 51, 61,
and 62, and difference NOE and COSY spectra for 27, 28, and
42. This material is available free of charge via the Internet at
JO8027592
3688 J. Org. Chem. Vol. 74, No. 10, 2009