2,2′-Bis(2-indenyl)biphenyl Derivatives
J . Org. Chem., Vol. 67, No. 1, 2002 175
ethanol/water 9:1 v/v, and treated with active carbon. Cooling
followed by slow partial evaporation gave a yellow-brown solid
powder (1.08 g, 58%). An analytical pure sample was obtained
by crystallization from acetone/ethanol 1:1 v/v by slow evapo-
To a solution of 41 (6.50 g; 24.9 mmol) in THF (65 mL) and
methanol (35 mL) was added sodium borohydride (1.03 g; 27.1
mmol) at 0 °C. A gas evolved, and the yellow color dissappeared
during this event. The ice bath was removed and stirred for 1
h at room temperature. A solution of hydrochloric acid in water
(5%, 100 mL) was added to the reaction mixture. The reaction
mixture was extracted with dichloromethane (2 × 150 mL).
The combined organic phases were dried over sodium sulfate
and filtered. The organic solvents were removed under reduced
pressure to give 6.54 g (100%) of white powder of 44. 1H NMR
(CDCl3): δ 8.14 (d, J ) 8.1 Hz, 1H), 7.76 (m, 2H), 7.43 (m,
2H), 7.26 (d, J ) 8.3 Hz, 1H), 5.38 (d, J ) 4.9 Hz, 1H), 4.77
(m, 1H), 3.43 (d, J ) 6.4 Hz, 2H) ppm.
1
ration in air, mp 158-159 °C. H NMR (CDCl3): δ 7.7 (d, J )
8.0 Hz, 1H), 7.68 (d, J ) 8.0 Hz, 1H), 7.59 (d, J ) 8.0 Hz, 1H),
6.8-7.5 (m, 13H), 6.47 (s, 1H), 5.03 (s, 1H), 3.72 (d, J ) 16
Hz, 1H), 3.46 (d, J ) 16 Hz, 1H), 2.70 (s, 2H) ppm. 13C NMR
(CDCl3): δ 150.0, 148.8, 147.0, 144.5, 144.2, 143.0, 142.5, 140.1,
139.6, 129.5, 128.4, 127.1, 127.0, 126.7, 126.0, 125.6, 124.9,
124.5, 124.1, 123.6, 123.5, 122.9, 122.1, 120.0, 119.5, 63.2, 57.3,
43.8, 40.7 ppm. Anal. Calcd for C30H22
Found: C, 94.05; H, 5.84.
: C, 94.20; H, 5.80.
2,2′-Bip h en yl Dibor on ic Acid (31). To a suspension of
2,2′-dilithiobiphenyl bis TMEDA adduct (16) (62.1 g; 156
mmol) in diethyl ether (1000 mL), kept at -40 °C (with a dry
ice/acetone bath), trimethoxyborane (80 mL; 73.2 g; 705 mmol)
was slowly added. The reaction mixture was allowed to warm
to room temperature and then stirred overnight. A sticky lump
had formed which was disolved by the addition of dry THF
(400 mL). The reaction mixture was stirred for an additional
1 h. To the resulting reaction mixture, water (200 mL) was
added, followed by hydrochloric acid (5%, 500 mL). The
reaction mixture was vigorously stirred for 4 h. The organic
solvents were removed under reduced pressure. The remaining
aqueous phase was extracted with dichloromethane (3 × 300
mL). The combined organic phases were dried over sodium
sulfate. The drying agent was filtered off, and the solvents
were removed under reduced pressure. Pure white microcrys-
talline 31 was obtained after crystallization from toluene/
ligroin (23.9 g, 63%), mp 140 °C (dec). 1H NMR (DMSO-d6): δ
9.15 (bs, 4H), 7.72 (d, J ) 8.0 Hz, 2H), 7.57 (m, 4H), 7.37 (dt,
J ) 8.0 Hz and J ) 1.6 Hz) ppm. 13C NMR (DMSO-d6): δ 145.2,
134.1, 133.7, 130.7, 129.4, 126.5 ppm. Anal. Calcd for
The crude indanol (44) was dissolved in toluene (150 mL),
and p-toluenesulfonic acid (0.82 g; 4.3 mmol) was added. The
mixture was heated to reflux for 2 h, and a Dean-Stark trap
removed the evolved water. The mixture was cooled to room
temperature and extracted subsequently with a saturated
sodium carbonate solution and water. The solvents were
removed under reduced pressure. Filtration of the residue over
silica (eluent: ligroin) gave 35 as a light yellow solid (3.23 g,
1
53%), mp 92.0-93.8 °C. H NMR (CDCl3): δ.8.0-7.1 (m, 7H),
3.83 and 3.68 (2 s, sum: 2H), mixture of two double bond
isomers. 13C NMR (CDCl3): δ 142.3, 141.1, 141.0, 139.9, 134.3,
133.3, 132.1, 131.5, 130.1, 129.6, 129.2, 128.3, 127.5, 127.3,
126.7, 126.0, 125.7, 125.6, 125.1, 124.3, 122.4, 120.2, 47.4, 45.3
ppm, mixture of two double bond isomers. Anal. Calcd for
C
13H9Br: C, 63.70; H, 3.70. Found: C, 63.55; H, 3.69.
2-Br om oben z(5,6)in d en e (36). 2-Bromobenz(4,5)indanone
(42) was prepared in the same way as 41 from 39 with the
difference that the reaction mixture was extracted with
dichloromethane instead of diethyl ether. The solvents were
removed under reduced pressure, and the crude mixture of
the bromoindanone synthesis (9.78 g) was treated as described
in the synthesis for 44. After trituration with diethyl ether,
pure bromoindanol 45 was obtained (3.41 g, 36%). 1H NMR
(CDCl3): δ 7.75 (m, 3H), 7.61 (s, 1H), 7.30 (m, 2H), 5.05 (dd,
J ) 9.5 and 4.4 Hz, 1H), 4.91 (m, 1H), 3.48 (bs, 2H), 2.50 (d,
10.0 Hz) ppm. After dehydratation and crystallization from
ligroin, pure 36 (decomposes slowly at room temperature) was
obtained (1.72 g, 55%). 1H NMR (CDCl3): δ 7.73 (m, 3H), 7.60
(s, 1H), 7.37 (m, 2H), 6.96 (bs, 1H), 3.67 (tr, J ) 1.4 Hz, 2H)
ppm. 13C NMR (CDCl3): δ 142.6, 140.2, 133.1, 132.9, 131.6,
128.0, 127.9, 126.8, 125.6, 125.3, 121.7, 117.9, 44.8 ppm.
2,2′-Bis(2-in d en yl)bip h en yl (10) via th e Sta n d a r d Su -
zu k i P r oced u r e. To a solution of 21 (15.60 g; 80.0 mmol) in
degassed DME (800 mL) were added 31 (9.40 g; 38.8 mmol),
[Pd(PPh3)4] (3.23 g; 2.80 mmol), and a degassed solution of K2-
CO3 (16.72 g; 121 mmol) in water (400 mL). After stirring at
reflux overnight, the reaction mixture was poured in a solution
of hydrochloric acid in water (5%; 250 mL). The organic phase
was dried over sodium sulfate and filtered, and the solvents
were removed under reduced pressure. Crystallization of the
residue from ethanol gave analytically pure 10 (11.6 g, 79%),
mp 210-212 °C (lit. 211-213 °C).7
F ir st Gen er a tion Ar r a y HTE Ru n for th e Syn th esis of
10. The 48 reaction vessels were charged with 2-bromoindene
(50 mg; 0.256 mmol), 2,2′-biphenyl diboronic acid (31 mg; 0.128
mmol), and [Pd(PPh3)4] (3.0 mg; 2.60 µmol). To each vessel was
added the desired solvent (1 mL). Then, all bases were added
as aqueous stock solutions (2.0 M, except Bu4NF (1.0 M), 1.5
equiv per coupling). The reaction vessels were heated at 70
°C during 6 h. After cooling to room temperature, the reaction
mixtures were filtered, and the residues were extracted with
acetone. Combined filtrate and acetone extract were analyzed
by LC-MS.
C
12H12B2O4‚H2O: C, 64.39; H, 4.50. Found: C, 64.00; H, 4.56.
Bis-p in a col Ester of 2,2′-Bip h en yl Dibor on ic Acid (33).
A suspension of 2,2′-biphenyl diboronic acid (31) (1.00 g; 4.12
mmol) and pinacol (0.98 g; 8.24 mmol) in toluene (25 mL) was
heated under reflux with Dean-Stark trap for 16 h. During
the first hour, water separated. The solution was cooled, and
the resultant hazy solution was filtered and evaporated to
dryness to afford crude product. Analytical sample was
prepared by dissolving in ligroin (50 mL), filtering, and slowly
evaporating in air (to approximately 10 mL) to afford large
1
colorless platelike crystals (1.05 g, 63%), mp 109-110 °C. H
NMR (CDCl3): δ 7.6 (d, J ) 7.2 Hz, 2H), 7.2-7.4 (m, 6H), 1.0
(s, 24H) ppm. 13C NMR (CDCl3): δ 149.9, 134.0, 129.5, 129.4,
126.1, 83.5, 25.0 ppm. Anal. Calcd for C24H32B2O4: C, 70.98;
H, 7.94. Found: C, 71.18; H, 8.00.
2-Br om oben z(6,7)in d en e (35). Bromine (4.70 g; 29.6
mmol) was added to a suspension of phenyltrimethylammo-
nium bromide (6.39 g; 29.6 mmol) in THF (50 mL) at 0 °C.
The resulting red solution was brought to room temperature,
and this solution was added to a cold (0 °C) solution of benz-
(6,7)indanone (38) (5.39 g; 29.6 mmol) in THF (50 mL). The
ice bath was removed, and the resulting reaction mixture was
stirred overnight. The color had changed from yellow to
colorless, and a white precipitate had formed. Water (100 mL)
was added, and the mixture was extracted with diethyl ether
(2 × 200 mL). The organic phase was separated from the
aqueous phase. The organic phase was extracted with water
(3 × 75 mL), dried over sodium sulfate, and filtered. The
solvents were removed under reduced pressure, resulting in
a yellow oil containing some solid material. The 2-bromobenz-
(6,7)indanone (41) was precipitated from ethanol at -20 °C,
filtered, and washed with cold (-20 °C) ethanol twice, resulting
in 3.50 g (45%) of a yellow powder. A second fraction of a yellow
powder (1.36 g; 18%) was obtained after precipitation from the
concentrated mother liquor at -20 °C. 1H NMR (CDCl3): δ
9.0 (d, J ) 8.2 Hz, 1H), 8.0 (d, J ) 8.4 Hz, 1H), 7.82 (d, J )
8.0 Hz, 1H), 7.57 (m, 2H), 7.38 (d, J ) 8.4 Hz, 1H), 4.67 (dd,
J ) 7.2 and 2.8 Hz, 1H), 3.83 (dd, J ) 18.6 and 7.2 Hz, 1H),
3.42 (dd, J ) 18.6 and 2.8 Hz, 1H) ppm. 13C NMR (CDCl3): δ
198.8, 153.4, 136.3, 131.9, 128.5, 127.3, 126.9, 126.2, 123.0,
122.3, 51.5, 43.6, 37.2 ppm.
Secon d Gen er a tion Ar r a y HTE Ru n for th e Syn th esis
of 10. The 48 reaction vessels were charged with 2-bromoin-
dene (50 mg; 0.256 mmol) and 2,2′-biphenyl diboronic acid (31
mg; 0.128 mmol). Then, the 48 minireactors were divided in 4
blocks of 12 vessels, and those were charged with catalyst [Pd-
(PPh3)4] (8.9 mg; 7.71 µmol); [PdCl2(dppf)] (5.6 mg; 7.71 µmol);
Pd(OAc)2 (1.7 mg; 7.71 µmol) and Pd/C (5%, 10 mg). These 4
blocks of 12 mini reactors were each divided in blocks of 4 mini
reactors and each block of 4 reactors was charged with the