LETTER
Diversity-Oriented Synthesis of Biaryl Derivatives
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column chromatography using PE as eluent to afford 14 (110 mg,
74%) as a colorless liquid.
132.1, 133.5, 138.2, 147.5. HRMS(Q-ToF): m/z calcd for C15H19O
[M + H]+: 215.1436; found: 215.1433.
General Procedure for the Diels–Alder Reaction of Homoallyl
Butadiene Derivatives Followed by Aromatization
Compound 24
IR (neat): 1025, 1262, 1519, 1729, 2925 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.40 (dd, J1 = 8.8 Hz, J2 = 1.2 Hz, 2 H), 2.76 (t, J = 2.4
Hz, 2 H), 3.92 (s, 3 H), 3.94 (s, 3 H), 3.95 (s, 3 H), 3.97 (s, 3 H),
4.92–5.07 (m, 2 H), 5.81–5.89 (m, 1 H), 6.94 (d, J = 8.4 Hz, 1 H),
7.08 (d, J = 2.0 Hz, 1 H), 7.13–7.17 (m, 1 H), 7.58 (d, J = 2.0 Hz, 1
H), 8.02 (d, J = 1.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3):
d = 33.0, 35.4, 52.8, 56.14, 56.18, 56.2, 110.4, 111.6, 115.6, 119.8,
126.2. 128.9, 132.0, 132.4, 133.2, 137.5, 142.2, 149.5, 166.6, 169.8.
HRMS(Q-ToF): m/z calcd for C22H24O6 [M + Na]+: 407.1471;
found: 407.1482.
To a solution of the diene 14 (110 mg, 0.45 mmol) in toluene (5 mL)
was added dimethyl acetylene dicarboxylate (128 mg, 0.9 mmol),
and the reaction mixture was heated at 90 °C for 15 h. At the con-
clusion of the reaction (TLC monitoring) the solvent was removed
under reduced pressure, and the crude product was purified by a sil-
ica gel column chromatography (EtOAc–PE, 0.5:9.5) to afford the
adduct as a semisolid. Oxidation of the adduct was carried out with
MnO2 (116 mg, 13.05 mmol) in refluxing 1,4-dioxane (14 mL) for
30 h. The solvent was removed under reduced pressure, and the
crude product was purified by flash silica gel column chromatogra-
phy (EtOAc–PE, 0.5:9.5) to afford the aromatized product 24 (130
mg, 75%) as a semisolid.
Compound 26
IR (neat): 1013, 1266, 1435, 1640, 2952 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.40 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 2 H), 3.80 (t, J = 4.8
Hz, 2 H), 3.92 (s, 3 H), 3.96 (s, 3 H), 4.99–5.30 (m, 1 H), 5.81–5.89
(m, 1 H), 7.43 (d, J = 4.8 Hz, 1 H), 7.43 (d, J = 4.8 Hz, 1 H), 7.53
(d, J = 4.4 Hz, 1 H), 7.59 (d, J = 2.0 Hz, 2 H), 8.03 (d, J = 2.0 Hz, 2
H). 13C NMR (100 MHz, CDCl3): d = 32.9, 35.3, 52.7, 53.6, 115.7,
126.4, 128.5, 128.8, 129.2, 132.2, 134.0, 134.4, 137.3, 137.8, 140.3,
140.9, 166.3, 169.7. HRMS(Q-ToF): m/z calcd for C20H19O4Cl
[M + Na]+: 381.0882; found: 381.0870.
General Procedure for the Preparation of 1,3-Dienes and Diels–
Alder Reaction Followed by Aromatization
A solution of 13 (100 mg, 0.61 mmol) in toluene (10 mL) was de-
gassed with N2 for 10 min and then Grubbs second-generation cat-
alyst (26 mg, 5 mol%) was added. The reaction mixture was kept
under 1 atm pressure of ethylene (balloon pressure) and stirred at
90 °C for 24 h. At the conclusion of the reaction (TLC monitoring)
the solvent was concentrated, and the crude product was purified by
a flash silica gel column chromatography (EtOAc–PE, 0.5:9.5) to
afford 29 (85 mg, 73%) as a brownish liquid. Later, diene 29 (95
mg, 0.5 mmol) was dissolved in toluene (10 mL), dimethyl acety-
lene dicarboxylate (142 mg, 1.0 mmol) was added, and the mixture
was heated at 90 °C for 24 h. At the conclusion of the reaction (TLC
monitoring) the adduct was oxidized with DDQ (181 mg, 0.79
mmol) in refluxing toluene (10 mL) for 36 h. The solvent was re-
moved under reduced pressure, and the crude product obtained was
purified by flash silica gel column chromatography with 5%
EtOAc–PE to afford the aromatized product 34 (110 mg, 66%) as a
semisolid.
Compound 34
IR (neat): 738, 1025, 1266, 1731, 2954 cm–1. 1H NMR (400 MHz,
CDCl3): d = 3.92 (s, 3 H), 3.93 (s, 3 H), 3.95 (d, J = 7.2 Hz, 6 H),
6.96 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 1.2 Hz, 1 H), 7.18 (d, J1 = 5.2
Hz, 1 H), 7.69 (d, J = 2.0 Hz, 1 H), 7.83 (d, J = 1.2 Hz, 1 H). 13
C
NMR (100 MHz, CDCl3): d = 56.8, 52.9, 56.1, 56.2, 110.2, 110.3,
111.5, 119.9, 126.9, 129.1, 131.8, 133.9, 144.4, 149.5, 149.7, 167.6,
168.8. HRMS(Q-ToF): m/z calcd for C18H19O6 [M + H]+: 331.1182;
found: 331.1185.
Compound 38
IR (neat): 748, 819, 1735, 2853 cm–1. 1H NMR (400 MHz, CDCl3):
d = 3.93 (s, 3 H), 3.94 (s, 3 H), 7.26–7.36 (m, 2 H), 7.69–7.79 (m, 1
H), 7.78–7.86 (m, 4 H). 13C NMR (100 MHz, CDCl3): d = 52.8,
52.9, 94.7, 127.2, 129.1, 130.0, 133.3, 138.5, 138.6, 143.3, 167.6,
168.3. HRMS(Q-ToF): m/z calcd for C16H14O4I [M + H]+:
393.9937; found: 393.9933.
General Procedure for Cross-Coupling Reactions
A solution of 37 (74 mg, 0.21 mmol) in THF–toluene (1:1) mixture,
4-methoxy phenylboronic acid (63 mg, 0.48 mmol) and aq Na2CO3
(44 mg, 0.42 mmol) was degassed with N2 for 20 min, and
Pd(PPh3)4 (9.7 mg, 4 mol%) was added. The reaction mixture was
then heated for 6 h at 90 °C. At the conclusion of the reaction (TLC
monitoring) the reaction mixture was diluted with H2O and extract-
ed with CH2Cl2 (4 × 50 mL). The combined organic layers were
washed with H2O, brine, and dried over Na2SO4. The solvent was
evaporated, and the crude product was purified by silica gel column
chromatography EtOAc–PE, 0.5:9.5) to give the desired cross-
coupling product 39 (68 mg, 86%) as a white solid.
Compound 39
Mp 150–152 °C. IR (KBr): 743, 819, 1734, 2852 cm–1. H NMR
1
(400 MHz, CDCl3): d = 3.87 (s, 3 H), 3.93 (s, 3 H), 3.95 (s, 3 H),
7.01, (d, J = 4.0 Hz, 2 H), 7.58 (d, J = 4.8 Hz, 2 H), 7.67 (d, J = 2.0
Hz, 2 H), 7.80 (d, J = 1.6 Hz, 2 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.94
(d, J = 1.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): d = 26.7, 29.7,
55.4, 114.3, 126.7, 126.8, 127.3, 127.4, 127.8, 128.2, 128.8, 129.0,
129.1, 133.9, 140.9, 159.2. HRMS(Q-ToF): m/z calcd for C23H21O5
[M + H]+: 377.1398; found: 377.1389.
Compound 15
IR (neat): 790, 1220, 1590, 2985 cm–1. 1H NMR (400 MHz, CDCl3):
d = 3.92 (s, 3 H), 3.95 (s, 3 H), 6.95 (d, J = 4.4 Hz, 2 H), 7.11–7.16
(m, 1 H), 7.32 (t, J = 7.8 Hz, 1 H), 7.42 (t, J = 8.2 Hz, 2 H), 7.56 (d,
J = 4.4 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 53.5, 56, 110,
111, 119, 127, 128, 134, 141, 148, 149. HRMS(Q-ToF): m/z calcd
for C14H15O2 [M + H]+: 215.1078; found: 215.1072.
Compound 40
Mp 138–140 °C. IR (KBr): 743, 819, 1734, 2852 cm–1. H NMR
1
(400 MHz, CDCl3): d = 3.94 (s, 3 H), 3.96 (s, 3 H), 7.71–7.94 (m, 5
H), 7.81 (d, J = 2.0 Hz, 2 H), 7.87 (d, J1 = 8.4 Hz, 2 H), 7.95 (d,
J = 2.0 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 52.9,
55.5,114.4, 114.5, 119.0, 127.3, 127.6, 128.0, 128.7, 129.8, 132.9,
133.3, 137.3, 139.4, 141.1, 143.5, 153.6, 156.8. HRMS(Q-ToF):
m/z calcd for C23H17NO4 [M + Na]+: 394.1068; found: 394.1055.
Compound 20
1
IR (neat): 742, 811, 1263, 1514, 1601, 2929 cm–1. H NMR (400
MHz, CDCl3): d = 2.15–2.23 (m, 4 H), 3.81 (s, 3 H), 4.95–5.03 (m,
3 H), 5.12 (d, J = 1.6 Hz,1 H), 5.64–5.71 (m, 1 H), 5.78–5.85 (m, 1
H), 6.30 (d, J = 15.6 Hz, 1 H), 6.86 (d, J = 1.2 Hz, 2 H), 7.25 (d,
J = 0.9 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 21.1, 32.4, 33.6,
55.3, 60.5, 113.5, 114.1, 114.3, 115.0, 126.8, 128.2, 128.8, 129.4,
Compound 41
Mp 157–159 °C. IR (KBr): 740, 823, 1682, 1730, 2853 cm–1. H
1
NMR (400 MHz, CDCl3): d = 2.65 (s, 3 H), 3.94 (s, 3 H), 3.95 (s, 3
H), 7.73–7.74 (m, 7 H), 7.83 (dd, J1 = 2.8 Hz, J2 = 8.0 Hz, 1 H), 7.96
Synlett 2011, No. 16, 2329–2334 © Thieme Stuttgart · New York