Synthesis of Biaryls
J . Org. Chem., Vol. 66, No. 18, 2001 6089
reflux gently, and the rate of addition was controlled to
maintain gentle reflux. At the end of the addition, refluxing
was continued for 4 h, and the mixture was then cooled to room
temperature and added over 1.5 h to a stirred and cooled (-78
°C) solution of chlorobis(diethylamino)phosphine34 (4.938 g,
23.5 mmol) in Et2O (50 mL). The mixture was stirred overnight
with the ice bath being left in place but not recharged. The
mixture was then refluxed for 30 min, cooled (ice bath), and
stirred while HCl was bubbled into it for ∼1 h. The cold bath
was removed, and the mixture was stirred for 2 h and then
filtered. The filtrate was concentrated (rotary evaporator,
water-pump, protection from moisture) and distilled under
reduced pressure (110°/0.2 mmHg) to give 2-naphthalenyl-
phosphonous dichloride [2-C10H7PCl2] as a yellow oil. A mix-
ture of dry MeOH (25 mL) and hexane (10 mL) was added
slowly (∼2 h) under N2 to a stirred and cooled (0 °C) solution
of the oil in hexane (30 mL) (N2 atmosphere). Stirring was
continued for 1 h, at which stage the ice bath was removed.
When the mixture had attained room temperature, it was
evaporated on a rotary evaporator (protection from moisture),
and the residual dimethyl 2-naphthalenylphosphonite [2--
C10H7P(OMe)2] was used in the next step without further
purification.
(s′), 132.3 (s′), 132.4 (d′), 133.7 (d′), 133.8 (d′), 141.6 (s′), 141.7
(s′). Exact mass m/z calcd for C19H1879BrO2P, 388.02277; found,
388.02250.
(2-Br om op h en yl)cya n om et h yl Dip h en ylp h osp in a t e
(33a ). The general procedure for acylation was followed, using
neat Ph2P(O)Cl23 (0.180 g, 0.15 mL, 0.76 mmol), R-hydroxy-
(2-bromobenzene)acetonitrile35 (0.161 g, 0.76 mmol), Et3N (1
mL), and DMAP (∼6 mg, 0.05 mmol) in CH2Cl2 (10 mL).
Evaporation of the solvent and flash chromatography of the
residue over silica gel (2.5 cm × 20 cm), using 1:2 EtOAc-
hexane, gave 33a (0.283 g, 90%) as a thick, yellow oil. FTIR
1
(CH2Cl2 cast): 3059, 1959, 1439, 1232 cm-1. H NMR (CDCl3,
360 MHz): δ 6.46 (d, J ) 10.0 Hz, 1H), 7.25 (dt, J ) 7.8, 1.8
Hz, 1H), 7.33-7.44 (m, 3H), 7.47-7.56 (m, 4H), 7.56-7.64 (m,
1H), 7.67-7.77 (m, 3H), 7.86-7.95 (m, 2H). 13C NMR (CDCl3,
75.5 MHz): δ 63.2 (d′), 63.3 (d′), 115.6 (s′), 115.7 (s′), 122.3
(s′), 128.3 (d′), 128.6 (d′), 128.8 (d′), 128.9 (d′), 129.1 (s′), 129.4
(d′), 130.5 (s′), 130.9 (s′), 131.5 (d′), 131.6 (d′), 131.76 (d′), 131.79
(d′), 131.9 (d′), 132.42 (s′), 132.48 (s′), 132.89 (d′), 132.92 (d′),
133.15 (d′), 133.19 (d′), 133.5 (d′). Exact mass m/z calcd for
C
20H15NO2P (M - Br), 332.08405; found, 332.08417.
1-(2-Br om oph en yl)eth en yl Diph en ylph osph in ate (34a).
A solution of LDA was prepared by dropwise addition of n-BuLi
(2.5 M in hexane, 1.44 mL) to a stirred and cooled (0 °C)
solution of i-Pr2NH (0.364 g, 0.50 mL, 3.60 mmol) in THF (10
mL). Stirring at 0 °C was continued for 20 min, and a solution
of 1-(2-bromophenyl)ethanone37 [(0.597 g, 3.00 mmol), made
from 2-bromo-R-methylbenzenemethanol23,24 by PCC oxidation]
in THF (20 mL) was added dropwise. Stirring at 0 °C was
continued for 1 h, and neat Ph2P(O)Cl23 (0.851 g, 0.69 mL, 3.6
mmol) was then injected. Stirring was continued for 30 min
at 0 °C, and the mixture was then quenched with water at 0
°C and extracted with Et2O. The combined organic extracts
were dried (MgSO4) and evaporated. Flash chromatography
of the residue over silica gel (3 cm × 25 cm), using 1:1 EtOAc-
hexane, gave 34a (0.958 g, 80%) as a colorless liquid. FTIR
(b) Meth yl Meth yl-2-n a p h th a len ylp h osp h in a te. The
crude phosphonite was added to stirred MeI (3 mL) under N2
at room temperature, and the mixture was refluxed overnight.
The mixture was cooled, and flash chromatography over silica
gel (3.5 cm × 25 cm), using 10:1 EtOAc-hexane, gave methyl
methyl-2-naphthalenylphosphinate as a colorless oil (1.057 g,
20% overall from 2-bromonaphthalene). FTIR (CH2Cl2 cast):
3453, 3054, 2986, 2946, 2917, 2843, 1223 cm-1 1H NMR
.
(CDCl3, 360 MHz): δ 1.72 (d, J ) 14.8 Hz, 3H), 3.62 (d, J )
11.5 Hz, 3H), 7.57 (ddq, J ) 7.5, 7.5, 2.0 Hz, 2H), 7.65-7.72
(m, 1H), 7.84-7.89 (m, 1H), 7.89-7.96 (m, 2H), 8.42 (d, J )
14.2 Hz, 1H). 13C NMR (CDCl3, 75.5 MHz): δ 14.6 (q′), 16.0
(q′), 50.8 (q′), 50.9 (q′), 125.5 (d′), 125.7 (d′), 126.79 (d′), 126.81
(d′), 126.82 (d′), 127.0 (s′), 127.62 (d′), 127.64 (d′), 127.65 (d′),
128.1 (d′), 128.4 (d′), 128.5 (d′), 128.70 (s′), 128.72 (d′), 132.2
(s′), 132.4 (s′), 133.5 (d′), 133.6 (d′), 134.74 (s′), 134.77 (s′). Exact
mass m/z for C12H13O2P, 220.06532; found, 220.06515.
(c)1-(2-Br om oph en yl)eth yl Meth yl-2-n aph th alen ylph os-
p h in a te (32a , 32a ′). Methyl-2-naphthalenylphosphinic chlo-
ride [2-C10H7P(O)(Me)Cl] was made from methyl methyl-2-
naphthalenylphosphinate (0.364 g, 1.65 mmol) by treatment
with PCl5, according to a procedure reported13 for the corre-
sponding phenylphosphinate, and the compound was used
directly, without characterization.
(CH2Cl2 cast): 3057, 1646, 1439, 1290, 1233 cm-1 1H NMR
.
(CDCl3, 360 MHz): δ 4.87-4.92 (m, 1H), 5.35-5.40 (m, 1H),
7.09-7.27 (m, 3H), 7.34-7.43 (m, 4H), 7.44-7.55 (m, 3H),
7.78-7.88 (m, 4H). 13C NMR (CDCl3, 75.5 MHz): δ 104.12 (t′),
104.19 (t′), 121.8 (s′), 127.1 (d′), 128.3 (d′), 128.5 (d′), 130.1
(s′), 130.2 (d′), 131.0 (d′), 131.7 (d′), 131.8 (d′), 132.0 (s′), 132.3
(d′), 133.1 (d′), 137.16 (s′), 137.23 (s′), 151.6 (s′), 151.7 (s′). Exact
mass m/z calcd for C20H1679BrO2P, 398.00714; found, 398.00693.
1-(2-Br om oph en yl)eth en yl Bis(4-m eth oxyph en yl)ph os-
p h in a te (35a ). A solution of LDA was prepared by dropwise
addition of n-BuLi (2.5 M in hexane, 0.66 mL) to a stirred and
cooled (0 °C) solution of i-Pr2NH (0.167 g, 0.23 mL, 1.65 mmol)
in THF. Stirring at 0 °C was continued for 10 min, and then
1-(2-bromophenyl)ethanone37 [(0.272 g, 1.37 mmol) made from
2-bromo-R-methylbenzenemethanol23,24 by PCC oxidation] in
THF (10 mL) was added. Stirring was continued at 0 °C for 1
h. Bis(4-methoxyphenyl)phosphinic chloride [made from bis-
(4-methoxyphenyl)phosphinic acid23 (0.419 g, 1.51 mmol) and
SOCl2 (3 mL), as described above (see preparation of 24a )] in
THF (5 mL) was then injected dropwise, and stirring was
continued for 30 min at 0 °C. The mixture was quenched with
water at 0 °C and extracted with Et2O. The combined organic
extracts were dried (MgSO4) and evaporated. Flash chroma-
tography of the residue over silica gel (2.5 cm × 20 cm), using
1:1 EtOAc-hexane, gave 35a (0.395 g, 63%) as a light brown
The general procedure for acylation was followed, using the
above methyl-2-naphthalenylphosphinic chloride, 2-bromo-R-
methylbenzenemethanol23,24 (0.362 g, 1.80 mmol), Et3N (1 mL),
and DMAP (∼6 mg, 0.05 mmol) in dry CH2Cl2 (20 mL).
Evaporation of the solvent and flash chromatography of the
residue over silica gel (3 cm × 20 cm), using 1:1 EtOAc-
hexane, gave a mixture of the two diastereoisomers 32a and
32a ′ (0.365 g in all, 57%) as a colorless liquid. Small amounts
of the individual isomers were obtained by flash chromatog-
raphy. Compound 32a FTIR (CH2Cl2 cast): 3055, 2981, 2929,
1224 cm-1. 1H NMR (CDCl3, 360 MHz): δ 1.46 (d, J ) 6.5 Hz,
3H), 1.69 (d, J ) 14.5 Hz, 3H), 5.87 (dq, J ) 10.0, 6.5 Hz, 1H),
7.08-7.18 (m, 1H), 7.32-7.42 (m, 1H), 7.46-7.68 (m, 4H),
7.72-8.00 (m, 4H), 8.48 (d, J ) 13.0 Hz, 1H). 13C NMR (CDCl3,
75.5 MHz): δ 15.4 (q′), 16.7 (q′), 23.95 (q′), 24.00 (q′), 72.7 (d′),
72.8 (d′), 121.0 (s′), 125.6 (d′), 125.7 (d′), 127.0 (d′), 127.2 (d′),
127.86 (d′), 127.89 (d′), 128.3 (d′), 128.4 (d′), 128.6 (d′), 128.7
(s′), 129.0 (d′), 129.2 (d′), 130.4 (s′), 132.4 (s′), 132.6 (s′), 132.8
(d′), 133.2 (d′), 133.3 (d′), 134.9 (s′), 142.0 (s′), 142.1 (s′). Exact
mass m/z calcd for C19H1879BrO2P, 388.02277; found, 388.02228.
Compound 32a ′ FTIR (CH2Cl2 cast): 3055, 2981, 2928, 1223
oil. FTIR (CH2Cl2 cast): 1645, 1598, 1503 cm-1 1H NMR
.
(CDCl3, 360 MHz): δ 3.80 (s, 6H), 4.86-4.89 (m, 1H), 5.32-
5.36 (m, 1H), 6.85-6.92 (m, 4H), 7.09-7.25 (m, 3H), 7.52 (dd,
J ) 8.0, 1.5 Hz, 1H), 7.69-7.79 (m, 4H). 13C NMR (CDCl3, 75.5
MHz): δ 55.3 (q′), 103.76 (t′), 103.83 (t′), 113.8 (d′), 114.0 (d′),
1
cm-1. H NMR (CDCl3, 360 MHz): δ 1.63 (d, J ) 6.2 Hz, 3H),
(35) (a) van Almsick, A.; Buddrus, J .; Ho¨nicke-Schmidt, P.; Laumen,
K.; Schneider, M. P. J . Chem. Soc., Chem. Commun. 1989, 1391-1393.
(b) We prepared R-hydroxy(2-bromobenzene)acetonitrile from 2-bro-
mobenzaldehyde and KCN at pH 4.0, by the method given in ref 36.
(36) Sol´ıs, A.; Luna, H.; Pe´rez, H. I.; Manjarrez, N.; Sa´nchez, R.
Tetrahedron Lett. 1998, 39, 8759-8762.
1.79 (d, J ) 14.5 Hz, 3H), 5.67 (dq, J ) 10.0, 6.2 Hz, 1H), 6.98-
7.04 (m, 1H), 7.28-7.31 (m, 2H), 7.38-7.59 (m, 4H), 7.68-
7.84 (m, 3H), 8.28 (d, J ) 13.0 Hz, 1H). 13C NMR (CDCl3, 75.5
MHz): δ 15.5 (q′), 16.9 (q′), 24.43 (q′), 24.46 (q′), 73.0 (d′), 73.1
(d′), 121.0 (s′), 125.6 (d′), 125.8 (d′), 126.8 (d′), 127.5 (d′), 127.65
(d′), 127.71 (d′), 128.1 (d′), 128.3 (d′), 128.9 (d′), 129.0 (d′), 129.1
(37) Fleming, I.; Woolias, M. J . Chem. Soc., Perkin Trans. 1 1979,
829-837.