2.28–2.35 (2H, m, CH2CH2C O), 2.35 (1H, d,
J
18,
warmed to room temperature, stirred for a further 13 h, diluted
with EtOAc (40 mL) and washed with 5% HCl (10 mL). Drying
(MgSO4) and evaporation gave the crude product as a brown tar.
Purification by silica gel chromatography (EtOAc : pet. ether, 1 : 1
as eluent, cooled to 0 ◦C) gave the title compound 9 (28 mg, 44%)
as a light brown oil. nmax/cm-1 (film) 3296 (br), 2962, 1734, 1640,
1595, 1523, 1496 and 1240; dH (500 MHz, CDCl3) 1.23 (3H, s,
Me), 1.83–1.90 (1H, m, CHH), 1.96–2.04 (1H, m, CHH), 2.12
(1H, d, J 18, CHH), 2.28–2.32 (2H, m, CH2), 2.32 (1H, d, J 18,
CHH), 4.40 (1H, brs, NH), 4.50 (2H, d, J 5.6, CH2Ph), 5.63 (1H,
d, J 11, H1), 5.87 (1H, d, J 16, H8), 6.12 (1H, dd, J 16, 10, H7),
6.31 (1H, t, J 12, H4), 6.34 (1H, dd, J 16, 10, H6), 6.75 (1H,
dd, J 15, 12, H5), 6.94 (1H, t, J 12, H2), 7.24–7.32 (5H, m, aryl)
and 7.41 (1H, t, J 12, H3); dC (126 MHz, CDCl3) 26.0 (Me), 35.8
(CH2), 36.8 (CH2), 42.2 (CMe), 43.7 (CH2NH), 51.4 (CH2), 124.9,
126.4, 127.8, 127.7, 127.7, 128.1, 128.8, 128.9, 135.4, 135.9, 136.2,
MeCCHHC O), 3.72 (3H, s, OMe), 5.65 (1H, d, J 11,
CHCO2Me), 6.10 (1H, d, J 15.5, MeCCH ), 6.56 (1H, t, J 11,
CH CH–CO2Me) and 7.41 (1H, dd, J 15.5, 11, MeCCH CH);
dC (126 MHz, CDCl3) 25.5 (Me), 35.3 (CH2), 36.8 (CH2), 42.5
(CMe), 51.3 (OMe), 51.6 (CH2), 116.9 (alkene), 124.1 (alkene),
145.0 (alkene), 151.0 (alkene), 166.9 (CO2Me) and 218.1 (C O);
LRMS (ES+) m/z 278 (M + NH4 , 100%), 261 (M + H+),
+
229; HRMS (ES+) 226.1437 (C12H20NO3, M + NH4 , requires
+
226.1438).
(2Z,4Z,6E,8E)-9-(1-Methyl-3-oxo-cyclopentyl)-nona-2,4,6,8-
tetraenoic acid methyl ester 14
A solution of iodide 6 (210 mg, 0.80 mmol) and olefin 12 (200 mg,
1.6 mmol) in dry MeCN (4 mL) in a dry Schlenk tube under
argon was degassed using the freeze–pump–thaw method (1¥),
palladium(II) acetate (8 mg, 0.086 mmol) and silver(I) acetate
(170 mg, 1.02 mmol) were added, the mixture was further degassed
(2¥) and heated to 60 ◦C with vigorous stirring in the absence
of light. After 2.5 h the mixture was cooled, diluted with Et2O
(60 mL), passed through Celite and washed with sat. aq. NaHCO3
(10 mL) and brine (10 mL). Drying (MgSO4) and evaporation
gave the crude product as a brown oil. Purification by silica gel
chromatography (EtOAc : pet. ether, 1 : 9 then 1 : 4 cooled to 0 ◦C
as eluent) gave the title compound 14 (120 mg, 58%, 5 : 1 mixture
with minor Z,E,E,E-isomer 15) as a light red oil. nmax/cm-1 (film)
2951, 1736, 1707, 1593, 1446, 1209 and 1164; dH (700 MHz,
CDCl3) 1.20 (3H, s, CMe), 1.83 (1H, m, CHH), 1.98 (1H, m,
CHH), 2.09 (1H, d, J 18, CHH), 2.27 (2H, m, CH2), 2.30 (1H,
d, J 18, CHH), 3.73 (3H, s, OMe), 5.67 (1H, d, J 12, H1), 5.86
(1H, d, J 16, H8), 6.10 (1H, dd, J 16, 11, H7), 6.33 (1H, dd, J
15, 11, H6), 6.34 (1H, t, J 12, H4), 6.68 (1H, dd, J 15, 12, H5),
7.06 (1H, t, J 12, H2) and 7.25 (1H, t, J 12, H3); dC (176 MHz,
CDCl3) 26.0 (CMe), 35.8 (CH2), 36.8 (CH2), 42.3 (CMe), 51.4
(CH2), 51.5 (OMe), 117.4 (alkene), 124.6 (alkene), 126.2 (alkene),
127.6 (alkene), 137.1 (alkene), 137.3 (alkene), 138.7 (alkene), 144.4
(alkene), 167.0 (CO2Me) and 218.5 (ketone); LRMS (ES+) m/z 226
143.7, 166.2 and 218.8; LRMS (ES+) m/z 226 (M + NH4 , 100%),
+
209 (M + H+), 177; HRMS (ES+) 336.1960 (C22H26NO2 , M + H+
+
requires 336.1958).
2,2¢-Iodoformyl biphenyl 18
A stirred solution of 1,2-diiodobenzene (0.99 g, 3.0 mmol), cae-
sium(I) fluoride (1.8 g, 12 mmol), 2-formylphenylboronic acid 17
(0.90 g, 2.0 mmol) and triphenylphosphine (16 mmol, 0.06 mmol)
in IPA (20 ml) and water (2 mL) was degassed by bubbling argon
through the suspension for 30 min. After further degassing using
freeze–pump–thaw (2 ¥ cycles), palladium(II) acetate (6.7 mg,
0.03 mmol) was added, and the solution evacuated and filled with
argon (3 ¥ cycles). After stirring under argon, at 35 ◦C for 4 h, the
reaction was cooled to room temperature, filtered through celite,
diluted with diethyl ether (150 mL) and washed with 5% HCl (2 ¥
50 mL), water (75 mL) and brine (75 mL). Drying (MgSO4) and
evaporation gave the crude product as a brown oil. Purification
by silica gel chromatography (pet. ether : EtOAc, 15 : 1 as eluent)
gave the title compound 18 as white needles (0.44 g, 48%). M.p. 89–
90.5 ◦C; dH (400 MHz, CDCl3) 7.04 (1H, dt, J 1.6, 7.7, meta ArH),
7.19 (1H, d, J 8.0, ortho ArH), 7.24 (1H, dd, J 1.6, 7.6, ortho ArH),
7.37 (1H, dt, J 1.2, 7.6, meta ArH), 9.69 (1H, d, J 0.8, CO2H);
dC (400 MHz, CDCl3) 99.0 (IC) 126.4, 127.1, 127.6, 128.7, 129.5,
129.7, 132.4, 132.6, 138.1, 141.9, 146.7, 190.4. All spectroscopic
and analytical data were identical to those stated in the literature.13
Also identified was an and oxidative biproduct [1,1¢-biphenyl]-
2,2¢¢dicarbaldehyde 20 as a yellow oil; dH (400 MHz, CDCl3) 7.35
(2H, dd, J 1.2, 7.6, ortho ArH), 7.59 (2H, t, J 7.6, meta ArH), 7.67
(2H, dt, J 1.6, 7.6, meta ArH), 8.05 (1H, dd, J 1.6, 7.6, ortho ArH),
9.83 (1H, d, J 0.6, COH); dC 128.7, 129.0, 131.9, 133(COH). All
spectroscopic and analytical data were identical to those stated in
the literature.14
(M + NH4 , 100%), 209 (M + H+), 177; HRMS (ES+) 278.1751
+
+
+
(M + NH4 , C16H24NO3 requires 278.1751).
(2Z,4Z,6E,8E)-9-(1-Methyl-3-oxo-cyclopentyl)-nona-2,4,6,8-
tetraenoic acid benzylamide 9
To a stirred solution of methyl ester 14 (50 mg, 0.19 mmol) in THF
◦
(3 mL) at 0 C under argon was added a solution of LiOH.H2O
(80 mg, 1.9 mmol) in water (3 mL) dropwise, the reaction was
stirred for 19 h, diluted with Et2O (40 mL), acidified with 5% HCl
(5 mL) and separated. Drying (MgSO4) and evaporation gave the
crude acid (62 mg) as a brown oil. dH (400 MHz, CDCl3) 1.24
(3H, s, Me), 1.82–1.87 (2H, m, CH2), 1.96–2.07 (1H, m, CHH),
2.13 (1H, d, J 18, CHH), 2.26–2.32 (1H, m, CHH), 2.34 (1H, d, J
18, CHH), 5.72 (1H, d, J 10, H1), 5.91 (1H, d, J 16, H8), 6.14 (1H,
dd, J 16, 11, H7), 6.38 (1H, dd, J 15, 11, H6), 6.40 (1H, t, J 10, H4),
6.72 (1H, dd, J 15, 10, H5), 7.18 (1H, t, J 10, H2) and 7.23 (1H,
t, J 10, H2). To a stirred solution of the crude acid in dry DCM
(3 mL) at 0 ◦C under argon was added CDI (30 mg, 0.19 mmol),
the mixture was stirred for 15 min and benzylamine (0.040 mL,
0.32 mmol) was added dropwise. The reaction was stirred for 9 h,
Methyl 2¢-iodobiphenyl-2-carboxylate 19
To a solution of biaryl aldehyde 18 (0.10 g, 0.33 mmol) in methanol
(2 mL), heated to 45 ◦C was added OxoneTM (0.20 g, 0.36 mmol)
portion-wise. After stirring for 40 h the mixture was cooled to room
temperature, diluted with EtOAc (50 mL), acidified with 5% HCl
(10 ml) and extracted with EtOAc (3 ¥ 20 ml). The organic extracts
were then washed with water (2 ¥ 40 mL) and brine (40 mL).
Drying (MgSO4) and evaporation gave the crude product and
1882 | Org. Biomol. Chem., 2011, 9, 1876–1886
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The Royal Society of Chemistry 2011
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