J. P. Simeone, J. R. Sowa / Tetrahedron 63 (2007) 12646–12654
12651
calculated by HPLC using calibrated curves of concentration
versus absorbance of the appropriate reference. Preparative
chromatography was either performed on a simple glass col-
umn packed with silica gel or on an Argonaut Flashmaster
Solo using Isolute silica gel columns. Palladium analyses
were performed by Schwarzkopf Microanalytical Labora-
tory. All isolated compounds were determined to be >97%
pure by HPLC at 220 and 254 nm.
(7.3 mg, 0.02 mmol). The product was purified on an Isolute
silica gel column using the Argonaut Flashmaster Solo (elut-
ing with 0–100% methylene chloride in hexanes, linear gra-
dient over 23 min) to provide the title compound as a white
solid (116 mg, 80%). H NMR (400 MHz, CDCl ) d: 10.07
1
3
(s, 1H), 8.19 (d, J¼8.3 Hz, 2H), 7.70 (d, J¼8.3 Hz, 2H), 7.65
1
3
(d, J¼7.4 Hz, 2H), 7.52–7.46 (m, 3H). C NMR (100 MHz,
CDCl ) d: 191.9, 147.2, 135.2, 130.3, 129.0, 128.4, 127.7,
3
127.3.
4
.2. General Suzuki–Miyuara cross-coupling procedure
0
26
4
.2.5. 2-Fluoro-4 -methylbiphenyl. The general proce-
A 10 mL recovery flask containing a magnetic stir bar was
charged with Pd/C (5 wt %, 50% water-wet, 85 mg,
dure was followed with 2-fluorophenylboronic acid (134 mg,
0.96 mmol), 4-chlorotoluene (95 mL, 0.8 mmol), and
MePhos (7.3 mg, 0.02 mmol). The product was purified on
an Isolute silica gel column using the Argonaut Flashmaster
Solo (eluting with 0–2% methylene chloride in hexanes, lin-
ear gradient over 20 min) to provide the title compound as
0
K CO (221 mg, 1.60 mmol), ligand (0.02 mmol), and
.02 mmol total Pd), aryl boronic acid (0.96 mmol),
2
3
2
and purged with nitrogen and the aryl chloride was added
0:1 v/v DMA:H O (5 mL). The mixture was degassed
2
ꢀ
1
(
0.8 mmol). The reaction was heated at 80 C for 24 h.
a colorless oil (105 mg, 71%). H NMR (400 MHz,
CDCl ) d: 7.47–7.44 (m, 2H), 7.42 (dd, J¼1.8, 7.8 Hz,
The reaction mixture was filtered over Celite and washed
with ethyl acetate. The ethyl acetate was then transferred
to a separatory funnel and washed with water and brine.
The organic layer was dried over sodium sulfate, filtered,
and concentrated in vacuo.
3
1H), 7.32–7.25 (m, 3H), 7.22–7.12 (m, 2H), 2.41 (s, 3H).
C NMR (100 MHz, CDCl ) d: 137.5, 130.7, 129.1,
128.9, 128.7, 128.6, 124.3, 116.1, 115.9, 21.2.
1
3
3
0
27
4
.2.6. 2,4 -Dimethylbiphenyl. The general procedure was
4
.2.1. 4-Methoxybiphenyl. The general procedure was fol-
lowed with phenylboronic acid (120 mg, 0.96 mmol), 4-
followed with o-tolylboronic acid (130 mg, 0.96 mmol),
4-chlorotoluene (95 mL, 0.8 mmol), and XPhos (9.5 mg,
0.02 mmol). The product was purified on silica gel (eluting
chloroanisole (97 mL, 0.8 mmol), and MePhos (7.3 mg,
0.02 mmol). The product was purified on silica gel (eluting
with 2% ethyl acetate in hexane) to provide the title com-
with hexanes) to provide the title compound as a colorless
oil (132 mg, 91%). H NMR (400 MHz, CDCl ) d: 7.26–
1
3
1
13
pound as a white powder (97 mg, 66%). H NMR
(
7.21 (m, 8H), 2.40 (s, 3H), 2.27 (s, 3H). C NMR
(100 MHz, CDCl ) d: 141.8, 139.0, 136.3, 135.4, 130.2,
129.8, 129.0, 128.7, 127.0, 125.7, 21.1, 20.4.
400 MHz, CDCl ) d: 7.56–7.51 (m, 4H), 7.43–7.40 (m,
3
3
2
H), 7.32–7.28 (m, 1H), 7.00–6.97 (m, 2H), 3.86 (s, 3H).
C NMR (100 MHz, CDCl ) d: 159.1, 140.8, 133.7,
28.7, 128.1, 126.7, 126.6, 114.2, 55.3.
1
3
3
2
6
1
4.2.7. 2-Methylbiphenyl. The general procedure was
followed with phenylboronic acid (120 mg, 0.96 mmol),
2-chlorotoluene (95 mL, 0.8 mmol), and XPhos (9.5 mg,
0.02 mmol). The product was purified on silica gel (eluting
0
23
4
.2.2. 4 -Methoxybiphenyl-4-carbaldehyde. The general
procedure was followed with 4-formylphenylboronic acid
144 mg, 0.96 mmol), 4-chloroanisole (97 mL, 0.8 mmol),
(
with hexanes) to provide the title compound as a colorless
oil (95 mg, 71%). H NMR (400 MHz, CDCl ) d: 7.43–7.38
1
and MePhos (7.3 mg, 0.02 mmol). The product was purified
on an Isolute silica gel column using the Argonaut Flashmas-
ter Solo (eluting with 0–100% methylene chloride in hex-
anes, linear gradient over 23 min) to provide the title
3
(m, 3H), 7.35–7.31 (m, 3H), 7.27–7.21 (m, 3H), 2.23 (s,
3H). C NMR (100 MHz, CDCl ) d: 141.9, 135.3, 130.3,
129.8, 129.2, 128.0, 127.2, 126.7, 125.7, 20.4.
1
3
3
1
compound as a white solid (50 mg, 30%). H NMR
400 MHz, CDCl ) d: 10.03 (s, 1H), 7.92 (dd, J¼1.7,
0
25
(
6
4.2.8. 2,2 -Dimethylbiphenyl. The general procedure was
followed with 2-methylphenylboronic acid (130 mg,
0.96 mmol), 2-chlorotoluene (95 mL, 0.8 mmol), and XPhos
(9.5 mg, 0.02 mmol). The product was purified on silica gel
3
.5 Hz, 2H), 7.71 (d, J¼8.2 Hz, 2H), 7.59 (dd, J¼1.9,
1
3
6 C
NMR (100 MHz, CDCl ) d: 191.9, 160.1, 146.8, 134.7,
.7 Hz, 2H), 7.00 (dd, J¼2, 6.7 Hz, 2H), 3.86 (s, 3H).
3
1
32.0, 130.3, 128.4, 127.0, 114.4, 55.4.
(eluting with hexanes) to provide the title compound as a col-
orless oil (116 mg, 80%). H NMR (400 MHz, CDCl )
1
3
13
2
4
4.2.3. 4-Methylbiphenyl. The general procedure was
followed with phenylboronic acid (120 mg, 0.96 mmol), 4-
chlorotoluene (95 mL, 0.8 mmol), and MePhos (7.3 mg,
d: 7.27–7.20 (m, 6H), 7.10 (d, J¼6.8 Hz), 2.06 (s, 6H).
C
NMR (100 MHz, CDCl ) d: 141.6, 135.8, 129.8, 129.3,
3
127.1, 125.5, 19.8.
0
with hexanes) to provide the title compound as a white solid
.02 mmol). The product was purified on silica gel (eluting
0
13
4.2.9. 2-Methoxy-2 -methylbiphenyl. The general proce-
dure was followed with o-tolylboronic acid (130 mg,
0.96 mmol), 2-chloroanisole (102 mL, 0.8 mmol), and XPhos
(9.5 mg, 0.02 mmol). The product was purified on an Isolute
silica gel column using the Argonaut Flashmaster Solo (elut-
ing with 0–3% methylene chloride in hexanes, linear
1
(
82 mg, 61%). H NMR (400 MHz, CDCl ) d: 7.61–7.55
3
(
1
(
1
m, 2H), 7.51–7.47 (m, 2H), 7.44–7.39 (m, 2H), 7.31 (m,
H), 7.24 (d, J¼7.9 Hz, 2H), 2.39 (s, 3H). C NMR
3
1
3
100 MHz, CDCl ) d: 141.1, 138.3, 137.0, 129.5, 128.7,
27.2, 127.0, 21.1.
gradient over 20 min) to provide the title compound as a col-
orless oil (48 mg, 30%). H NMR (400 MHz, CDCl ) d:
2
5
1
4
.2.4. 4-Formylbiphenyl. The general procedure was
3
followed with 4-formylphenylboronic acid (144 mg,
.96 mmol), chlorobenzene (95 mL, 0.8 mmol), and MePhos
7.36–7.31 (m, 1H), 7.26–7.12 (m, 5H), 7.03–6.94 (m, 2H),
3.68 (s, 3H), 2.15 (s, 3H). C NMR (100 MHz, CDCl ) d:
3
1
3
0