Rotationally Restricted and Modular Biphenyl Building Blocks
4
4
25 °C): δ = 130.0, 131.4, 132.0, 133.2, 141.7, 167.4 ppm. MS (EI):
m/z (%) = 310.0 (30) [M]+, 292.0 (21) [M – H2O]+, 292.0 (21), 265.0
(100) [M – CO2]+, 248 (68), 186.0 (42), 150.1 (31).
8.2, JH,H = 2.2 Hz, 2 H), 7.54 (d, JH,H = 2.2 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 30.6, 128.8, 130.8, 131.5,
134.7, 136.6, 137.9 ppm. MS (EI): m/z (%) = 405.9, 407.9, 409.9,
411.9 [M]+. C14H10Br2Cl2 (408.94): calcd. C 41.12, H 2.46; found
C 40.98, H 2.48.
4,4Ј-Dibromobiphenyl-2,2Ј-dicarboxylic Acid (11): By applying the
same conditions as described above for the synthesis of 10, target
compound 11 was obtained from 2-amino-5-bromobenzoic acid as
4,4Ј-Dibromo-2,2Ј-bis(bromomethyl)biphenyl (15): By applying the
a deep-red powder (70%). M.p. 246–250 °C. TLC: Rf = 0.06 (ethyl same procedure as used for the synthesis of the dichloro compound
acetate). 1H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 7.05–7.20
14 described above, 4,4Ј-dibromobiphenyl-2,2Ј-dimethanol (13) was
(m, 2 H), 7.67–7.50 (m, 2 H), 7.94 (br. s, 2 H), 13.1 (br. s, 2 H) converted into 4,4Ј-dibromo-2,2Ј-bis(bromomethyl)biphenyl (15;
ppm. 13C NMR (100 MHz, CD3OD, 25 °C): δ = 121.4, 133.5, 63%). M.p. 147 °C. TLC: Rf = 0.27 (hexane/t-BME, 1:1). 1H NMR
2
134.7 ppm. MS (EI): m/z (%) = 397.9, 399.9, 401.9 [M]+.
(400 MHz, CDCl3, 25 °C): δ = 4.09 (d, JH,H = 10.3 Hz, 2 H), 4.26
2
3
(d, JH,H = 10.3 Hz, 2 H), 7.12 (d, JH,H = 8.2 Hz, 2 H), 7.50 (dd,
4,4Ј-Dichlorobiphenyl-2,2Ј-dimethanol (12): Under an inert gas,
3JH,H = 8.2, JH,H = 2.0 Hz, 2 H), 7.69 (4JH,H = 2.0 Hz, 2 H) ppm.
4
4,4Ј-dichlorobiphenyl-2,2Ј-dicarboxylic
acid
(10;
17.10 g,
13C NMR (100 MHz, CDCl3, 25 °C): δ = 30.7, 123.1, 131.98,
132.00, 134.0, 137.5, 138.4 ppm. MS (EI): m/z (%) = 493.7, 495.7,
497.7, 499.7 [M]+. C14H10Br4 (497.85): calcd. C 33.78, H 2.02;
found C 33.67, H 2.01.
54.96 mmol) was dissolved in dry THF (200 mL). NaBH4 (6.24 g,
0.165 mol, 3.0 equiv.) was added in portions keeping the tempera-
ture below 30 °C. After stirring at room temperature for 1 h,
BF3·Et2O (31.1 mL, 0.253 mol, 4.6 equiv.) was added dropwise to
the reaction mixture keeping the temperature between 10 and
25 °C. The mixture was stirred overnight and quenched with HCl
(5%), diluted with ethyl acetate (450 mL), and filtered through a
Celite pad. The brown solution was washed with satd. Na2CO3 and
then brine and dried with MgSO4. After evaporation of the sol-
vents, 4,4Ј-dichlorobiphenyl-2,2Ј-dimethanol (12) was obtained as
a brown oily solid (16.40 g), which was used without further purifi-
cation in the next step. For analytical purposes a sample was puri-
fied by flash chromatography (silica gel; hexane/ethyl acetate, 7:3).
2,2Ј-Diallyl-4,4Ј-dichlorobiphenyl (18): Under argon 2,2Ј-bis(bromo-
methyl)-4,4Ј-dichlorobiphenyl (14) (673 mg, 1.65 mmol) was dis-
solved in CH2Cl2 (15 mL). CuI (313 mg, 1.64 mmol, 1.0 equiv.) was
added at once, and the reaction mixture was cooled to –70 °C. In
the absence of light, vinylmagnesium bromide (9.4 mL, 6.58 mmol,
4.0 equiv., 0.7 ) in dry THF was slowly added dropwise to the
reaction mixture, and stirring was continued at –70 °C for 1 h. Af-
ter stirring overnight (0–25 °C), the reaction was quenched with
satd. NH4Cl (50 mL) and brine (50 mL). The mixture was extracted
with t-BME (3ϫ50 mL), separated, and the combined organic
phases were dried with MgSO4. The crude product was purified by
flash chromatography to afford 2,2Ј-diallyl-4,4Ј-dichlorobiphenyl
1
M.p. 121 °C. TLC: Rf = 0.15 (hexane/ethyl acetate, 7:3). H NMR
2
3
(250 MHz, [D6]DMSO, 25 °C): δ = 4.08 (dd, JH,H = 14.1, JH,H
=
2
3
5.4 Hz, 2 H), 4.19 (dd, JH,H = 14.1, JH,H = 5.4 Hz, 2 H), 5.26
3
3
3
(dd, JH,H1 = 5.4, JH,H2 = 5.4 Hz, 2 H), 7.11 (d, JH,H1 = 8.1 Hz, (18) as a smelly and colorless oil (290 mg, 0.96 mmol, 58%). TLC:
3
4
4
2 H), 7.36 (dd, JH,H = 8.1, JH,H = 2.3 Hz, 2 H), 7.58 (d, JH,H
=
Rf = 0.76 (hexane/CH2Cl2, 95:5). 1H NMR (400 MHz, CDCl3,
2
3
4
2.3 Hz, 2 H) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 25 °C): δ = 3.02 (dddd, JH,H = 15.5, JH,H = 6.6, JH,H1 = 1.5,
61.0, 127.2, 127.5, 131.7, 133.4, 136.4, 143.3 ppm. No accurate MS
was obtained. C14H12Cl2O2 (283.15): C 59.39, H 4.27; found C
59.40, H 4.23.
4JH,H2 = 1.5 Hz, 2 H), 3.08 (dddd, 2JH,H = 15.5, 3JH,H = 6.7, 4JH,H1
4
2
3
= 1.5, JH,H2 = 1.5 Hz, 2 H), 4.87 (dddd, JH,H1 = 1.7, JH,HZ
=
4
4
2
17.0, JH,H1 = 1.5, JH,H2 = 1.5 Hz, 2 H), 5.00 (dddd, JH,H = 1.7,
3JH,HE = 10.0, JH,H1 = 1.5, JH,H2 = 1.5 Hz, 2 H), 5.74 (dddd,
4
4
4,4Ј-Dibromobiphenyl-2,2Ј-dimethanol (13): Target compound 13
was synthesized by applying the same conditions as used for syn-
thesis of the dichloro compound 12 (67%). M.p. 133–134 °C. TLC:
Rf = 0.40 (hexane/ethyl acetate, 1:1). 1H NMR (400 MHz, [D6]-
3JH,H1 = 17.0, JH,H2 = 10.0, JH,H3 = 6.7, JH,H3 = 6.6 Hz, 2 H),
3
3
3
7.01 (d, 3JH,H = 8.0 Hz, 2 H), 7.19 (dd, 3JH,H = 7.8, 4JH,H = 2.2 Hz,
2 H), 7.36 (d, JH,H = 2.2 Hz, 2 H) ppm. 13C NMR (100 MHz,
4
CDCl3, 25 °C): δ = 37.9, 117.2, 126.6, 129.7, 131.6, 134.0, 136.4,
138.4, 140.3 ppm. MS (EI): m/z (%) = 302.1 (35) [M]+, 267.1 (98)
[M – Cl]+, 238.0 (62), 226.1 (100) [M – Cl – C3H5 (allyl)]+, 203.1
(66), 191.1 (61), 101.0 (20). C18H16Cl2 (303.23): calcd. C 71.30, H
5.32; found C 71.07, H 5.30.
2
3
DMSO, 25 °C): δ = 4.05 (dd, JH,H = 14.1, JH,H = 5.5 Hz, 4 H),
2
3
3
4.15 (dd, JH,H = 14.1, JH,H = 5.4 Hz, 2 H), 5.23 (dd, JH,H1
=
5.5, 3JH,H2 = 5.5 Hz, 2 H), 7.01 (d, 3JH,H1 = 8.1 Hz, 2 H), 7.47 (dd,
3JH,H = 8.0, JH,H = 1.9 Hz, 2 H), 7.69 (d, JH,H = 1.9 Hz, 2 H)
ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 61.0, 122.0,
130.1, 130.4, 131.9, 136.8, 143.4 ppm. MS (FAB): m/z (%) = 372.9
[M + H]+. C14H12Br2O2 (372.05): calcd. C 45.20, H 3.25; found C
44.63, H 3.43.
4
4
2,2Ј-Diallyl-4,4Ј-dibromobiphenyl (19): According to the procedure
used for the synthesis of 18 target compound 19 (79%) was ob-
tained as a colorless oil. TLC: Rf = 0.46 (hexane/CH2Cl2, 95:5). 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 3.13–2.97 (m, 4 H), 4.87 (dd,
2,2Ј-Bis(bromomethyl)-4,4Ј-dichlorobiphenyl (14): 4,4Ј-Dichlorobi-
phenyl-2,2Ј-dimethanol (12; 16.40 g, assuming 54.96 mmol) was
dissolved in dry CH2Cl2 (100 mL). The brown solution was cooled
to 5 °C, and PBr3 (12.9 mL, 0.136 mol, 2.5 equiv.) was slowly added
dropwise to the reaction mixture. After stirring at 0–25 °C (30 h),
water (40 mL) was carefully added to quench the reaction. The
aqueous phase was separated and extracted with CH2Cl2 (40 mL),
and the combined organic phases were filtered through a silica pad.
After evaporation of the solvents and purification by flash
chromatography (silica; CH2Cl2 in hexane, 10–80%), 2,2Ј-bis(bro-
momethyl)-4,4Ј-dichlorobiphenyl (14) was obtained as yellow crys-
tals (10.70 g, 26.17 mmol, 48% over two steps). M.p. 120–121 °C.
2JH,H = 1.6, JH,H = 17.0 Hz, 2 H), 5.01 (dd, JH,H = 1.6, JH,H
=
3
2
3
3
10.1 Hz, 2 H), 5.80–5.67 (m, 2 H), 6.95 (d, JH,H = 8.1 Hz, 2 H),
7.37 (dd, 3JH,H = 8.4, 4JH,H = 2.1 Hz, 2 H), 7.43 (d, 4JH,H = 2.4 Hz,
2 H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 37.3, 116.8,
121.8, 129.1, 131.3, 132.2, 135.9, 138.4, 140.1 ppm. MS (EI): m/z
(%) = 390.0, 392.0, 394.0 [M]+. C18H16Br2 (392.13): calcd. C 55.13,
H 4.11; found C 55.24, H 4.19.
3,10-Dichloro-5,8-dihydrodibenzo[a,c]cyclooctene (20): 2,2Ј-Diallyl-
4,4Ј-dichlorobiphenyl (18; 121 mg, 0.40 mmol) and Grubbs’ cata-
lyst (2nd generation, 20.4 mg, 24 µmol, 6.0 mol-%) was heated at
reflux in CH2Cl2 (30 mL). After 3 h, the solvent was evaporated,
TLC: Rf = 0.44 (hexane/CH2Cl2, 95:5). 1H NMR (400 MHz, and the crude product was purified by flash chromatography (silica
2
2
CDCl3, 25 °C): δ = 4.10 (d, JH,H = 10.3 Hz, 2 H), 4.25 (d, JH,H
gel; 0–5% CH2Cl2 in hexane) to yield 3,10-dichloro-5,8-dihydrodi-
benzo[a,c]cyclooctene (20) as an off-white solid (97 mg, 0.35 mmol,
3
3
= 10.3 Hz, 2 H), 7.19 (d, JH,H = 8.2 Hz, 2 H), 7.36 (dd, JH,H
=
Eur. J. Org. Chem. 2010, 120–133
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
127