12
K.S. Madden et al. / Tetrahedron 75 (2019) 130657
EtOAc in petroleum ether. Pure fractions were evaporated to yield
desired product as a bright yellow oil (0.470 g, 62%). 1H NMR
2-methoxybenzene (0.506 g, 1.30 mmol) was dissolved in dry,
degassed MeCN (7.8 mL) and added to a dry, argon-purged flask
containing Pd(OAc)2 (15 mg, 0.067 mmol), P(o-tol)3 (39 mg,
0.13 mmol) and AgOAc (0.232 g, 1.39 mmol). 4,4,6-Trimethyl-2-
vinyl-1,3,2-dioxaborinane (0.25 mL, 1.5 mmol) was then added
and the reaction mixture heated to 30 ꢀC for 18.5 h. The reaction
mixture was allowed to cool to room temperature, then diluted
with Et2O containing ~3 ppm BHT (19 mL) and passed through a
short Celite/silica plug. The solvent was evaporated to give 0.704 g
of crude product as a dark red viscous oil. The crude product was
purified by silica gel chromatography, elution gradient 0e10%
EtOAc in petroleum ether. Pure fractions were evaporated to give
desired product as a bright orange gum (0.289 g, 53%). 1H NMR
(600 MHz, CDCl3):
d 1.14e1.9 (1H, m), 1.46e1.55 (1H, m), 1.80 (1H,
dd, J ¼ 13.9, 2.9 Hz), 3.92 (3H, s), 4.24 (1H, dqd, J ¼ 12.3, 6.2, 3.0 Hz),
5.58 (1H, d, J ¼ 17.4 Hz), 6.39e6.55 (3H, m), 6.82 (1H, dd, J ¼ 15.5,
10.0 Hz), 6.82e6.92 (2H, m), 7.00 (1H, dd, J ¼ 17.3, 9.9 Hz), 7.45 (1H,
d, J ¼ 8.1 Hz); 11B NMR (128 MHz, CDCl3):
d
25.49; 13C NMR
d 23.3, 28.3, 31.4, 46.2, 56.3 (OMe), 65.0, 71.0,
(151 MHz, CDCl3):
109.5, 111.0, 120.3, 130.0, 132.7, 133.5, 134.8, 136.2, 138.2, 146.5,
10
156.1; LRMS (ASAP) [MþH] ¼ 391.1; HRMS (ASAP) [C
H BO3Br]
19 24
calculated 389.1038, found 389.1023.
Method 2: 1-Bromo-4-[(1E,3E)-4-iodobuta-1,3-dien-1-yl]-2-
methoxybenzene (1.0 g, 2.8 mmol) was dissolved in dry, degassed
MeCN (16 mL) and added to a dry, argon-purged flask containing
Pd(OAc)2 (31 mg, 0.14 mmol), P(o-tol)3 (83 mg, 0.27 mmol) and
(600 MHz, CDCl3):
d 1.24e1.6 (9H, m), 1.46e1.54 (1H, m), 1.79 (1H,
dd, J ¼ 13.8, 3.0 Hz), 3.92 (3H, s), 4.24 (1H, ddqd, J ¼ 12.3, 9.1, 6.0,
2.9 Hz), 5.55 (1H, d, J ¼ 17.3 Hz), 6.03e6.18 (1H, m), 6.39e6.44 (3H,
m), 6.48e6.52 (1H, m), 6.84e6.94 (3H, m), 6.95e7.04 (1H, m), 7.45
AgOAc
(0.491 g,
2.93 mmol).
4,4,6-Trimethyl-2-vinyl-1,3,2-
dioxaborinane (0.53 mL, 3.1 mmol) was then added and the reac-
tion mixture heated to 30 ꢀC for 18 h. The reaction mixture was
allowed to cool to room temperature then diluted with Et2O con-
taining ~3 ppm BHT (41 mL) and passed through a short Celite/silica
plug. The solvent was evaporated to give 1.10 g of crude product as a
viscous orange oil. The crude product was purified by silica gel
chromatography, elution gradient 0e10% EtOAc in petroleum ether.
Pure fractions were evaporated to yield desired product as a viscous
yellow oil (0.600 g, 56%).
(1H, d, J ¼ 8.1 Hz); 11B NMR (128 MHz, CDCl3):
d
25.37; 13C NMR
d 23.3, 28.3, 31.4, 46.2, 56.3, 64.9, 71.0, 109.6,
(151 MHz, CDCl3):
110.9, 120.2, 129.7, 130.0, 132.0, 133.5, 134.1, 134.2, 135.1, 135.8,
138.3, 146.7, 156.1; IR (nmax, cmꢁ1) 1568.7 (m), 1587.0 (m), 1607.7
(m), 2911.1 (m), 2938.7 (m), 2971.6 (m) inter alia; LRMS (ASAP)
10
[MþH] ¼ 417.1; HRMS (ESI) [C
H
BO3Br] calculated 415.1195,
21 26
found 415.1213.
4.2.12. 1-Bromo-4-[(1E,3E,5E)-6-iodohexa-1,3,5-trien-1-yl]-2-
methoxybenzene 20
4.2.14. Methyl (2E,4E,6E,8E,10E)-11-(4-bromo-3-methoxyphenyl)
The crude mixture containing 2-[(1E,3E,5E)-6-(4-bromo-3-
methoxyphenyl)hexa-1,3,5-trien-1-yl]-4,4,6-trimethyl-1,3,2-
dioxaborinane (0.60 g, 1.5 mmol) was dissolved in dry THF (5.7 mL)
and cooled to ꢁ78 ꢀC under argon. NaOMe (3.7 mL, 1.9 mmol,
0.50 M in MeOH) was added dropwise and then reaction mixture
stirred at ꢁ78 ꢀC for 40 min. Iodine monochloride (0.296 g,
1.59 mmol) in dry DCM (1.2 mL) was then added dropwise at this
temperature and the reaction mixture stirred at ꢁ78 ꢀC for a further
2 h. The reaction mixture was allowed to warm to room tempera-
ture and diluted with Et2O (47 mL), then washed with 5% Na2S2O3
(2 ꢂ 19 mL), H2O (19 mL) and brine (19 mL). The organics were
dried over MgSO4 under argon, filtered and evaporated to give a
bright yellow solid containing the desired product (1.26 mmol, 84%)
as determined by 1H NMR spectroscopy, which was found to
undeca-2,4,6,8,10-pentaenoate 4
Method
1:
2-[(E)-2-(4-Bromo-3-methoxyphenyl)ethenyl]-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (26 mg, 0.076 mmol),
methyl (2E, 4E, 6E,8E)-9-iodonona-2,4,6,8-tetraenoate (18 mg,
0.061 mmol), Pd(PPh3)4 (7.0 mg, 0.0061 mmol) and Ag2O (17 mg,
0.076 mmol) were added to a dry flask and the flask purged with
argon. Dry, degassed DME (0.46 mL) was then added and the re-
action stirred at 40 ꢀC for 17 h. The reaction mixture was then
diluted with EtOAc containing ~ 3 ppm BHT (6.0 mL) and passed
through a short plug of Celite/silica. The solvent was evaporated to
give 55 mg of a green residue. The crude product was purified by
silica gel chromatography at 0 ꢀC, eluent benzene, to give desired
product as a bright yellow solid (10 mg, 34%), mp 207.3e208.9 ꢀC.
1H NMR (700 MHz, CDCl3):
d 3.75 (3H, s, 3.92 (3H, s), 5.89 (1H, d,
rapidly decompose. 1H NMR (400 MHz, CDCl3):
d
3.93 (3H, s), 6.34
J ¼ 15.2 Hz), 6.37 (2H, ddd, J ¼ 15.1, 11.2, 4.3 Hz), 6.41e6.52 (3H, m),
6.55 (1H, d, J ¼ 15.5 Hz), 6.62 (1H, dd, J ¼ 14.7, 11.2 Hz), 6.80e6.85
(1H, m), 6.87e6.93 (2H, m), 7.29e7.35 (1H, m), 7.47 (1H, d,
(1H, dd, J ¼ 7.4, 1.2 MHz), 6.56e6.63 (2H, m), 6.81 (1H, dd, J ¼ 9.9,
7.6 Hz), 6.86e6.94 (3H, m), 7.11 (1H, dd, J ¼ 14.3, 10.6 Hz), 7.45e7.49
(1H, m). The compound was taken on to the next stage without any
further purification or characterisation.
J ¼ 8.1 Hz); 13C NMR (176 MHz, CDCl3):
d 51.7, 56.3, 109.6, 111.3,
120.3, 120.5, 129.7, 130.5, 132.6, 133.1, 133.5, 133.7, 135.4, 137.2,
138.0, 140.8, 144.7, 156.2, 167.7; IR (nmax, cmꢁ1) inter alia 1703.9 (m),
2912.8 (w), 2924.4 (w), 2938.4 (w), 2952.3 (w); LRMS (ASAP)
M ¼ 374.1; HRMS (ASAP) [C19H19O3Br] calculated 374.0499, found
4.2.13. 2-[(1E,3E,5E,7E)-8-(4-Bromo-3-methoxyphenyl)octa-
1,3,5,7-tetraen-1-yl]-4,4,6-trimethyl-1,3,2-dioxaborinane 21
Method 1: 1-Bromo-4-[(1E,3E,5E)-6-iodohexa-1,3,5-trien-1-yl]-
2-methoxybenzene (0.233 g, 0.60 mmol) was dissolved in dry,
degassed MeCN (3.7 mL) and added to a dry, argon-purged flask
containing Pd(OAc)2 (7.0 mg, 0.031 mmol), P(o-tol)3 (18 mg,
0.060 mmol) and AgOAc (0.109 g, 0.645 mmol). 4,4,6-Trimethyl-2-
vinyl-1,3,2-dioxaborinane (0.12 mL, 0.69 mmol) was then added
and the reaction mixture heated to 50 ꢀC for 20 h. The reaction
mixture was allowed to cool to room temperature, then diluted
with Et2O containing ~3 ppm BHT (25 mL) and passed through a
short Celite/silica plug. The solvent was evaporated to give 0.296 g
of crude product as a dark red viscous oil. The crude product was
purified by silica gel chromatography, elution gradient 0e10%
EtOAc in petroleum ether. Pure fractions were evaporated to give
desired product as a bright orange gum (0.146 g, 58%).
374.050. UV (CHCl3 5 mM, nm) 397 (ε 67 000), 417 (ε 56 000).
Fluorescence (CHCl3 100 nM, nm) 498, 527, 566, 594.
Method 2: 2-[(E)-2-(4-Bromo-3-methoxyphenyl)ethenyl]-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (26 mg, 0.076 mmol),
methyl (2E, 4E, 6E,8E)-9-iodonona-2,4,6,8-tetraenoate (18 mg,
0.061 mmol), Pd(OAc)2 (1.0 mg, 0.0061 mmol), PPh3 (5.0 mg,
0.018 mmol) and Ag2CO3 (34 mg, 0.12 mmol) were added to a dry
flask and the flask purged with argon. Dry, degassed MeCN
(0.46 mL) was then added and the reaction stirred at room tem-
perature for 17 h. The reaction mixture was then diluted with EtOAc
containing ~ 3 ppm BHT (6.0 mL) and passed through a short plug of
Celite/silica. The solvent was evaporated to give 82 mg of a green
residue. The crude product was purified by silica gel chromatog-
raphy at 0 ꢀC, eluent benzene, to give desired product as a bright
yellow solid (19 mg, 81%).
Method 2: 1-Bromo-4-[(1E,3E,5E)-6-iodohexa-1,3,5-trien-1-yl]-