The superbase-mediated pairwise substitution of the 2,2′- and 6,6′-positions in a biphenyl derivative

Article abstract of DOI:10.1002/ejoc.200300630

The superbasic mixture of butyllithium and potassium tertbutoxide is powerful enough to enable the double proton abstraction from one ortho and one ortho′ position of 4,4′-di-tert-butylbiphenyl. In this way, a series of functionalized derivatives becomes readily accessible, among them 4,4′-di-tert-butylbiphenyldiyl-2,2′-dicarboxylic acid (2a) and 4,4′-ditert-butylbiphenyl-2,2′-diol (2d). The latter compound can be subjected again to a superbase-promoted double metalation, thus giving rise to 2,2′,6,6′-tetrasubstituted biphenyl derivatives. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300630

FULL PAPER
The Superbase-Mediated Pairwise Substitution of the 2,2Ј- and 6,6Ј-Positions
in a Biphenyl Derivative
[a]
[a][‡]
Manfred Schlosser,*[a,b] Guiseppe Mangano, and Frederic Leroux
´ ´
Keywords: Protective groups / Carboxylation / Hydroxylation / Reductions / Superbase / Twofold metalation
The superbasic mixture of butyllithium and potassium tert-
butoxide is powerful enough to enable the double proton
abstraction from one ortho and one orthoЈ position of 4,4Ј-
di-tert-butylbiphenyl. In this way, a series of functionalized
derivatives becomes readily accessible, among them 4,4Ј-di-
tert-butylbiphenyldiyl-2,2Ј-dicarboxylic acid (2a) and 4,4Ј-di-
tert-butylbiphenyl-2,2Ј-diol (2d). The latter compound can be
subjected again to a superbase-promoted double metalation,
thus giving rise to 2,2Ј,6,6Ј-tetrasubstituted biphenyl derivat-
ives.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
enone[6] (4; 15%), but no 2-biphenylylcarboxylic acid (3a,
independently prepared from the monoiodobiphenyl 3c) at
all. Therefore, one has to impute the formation of the
monosubstituted derivatives 3b[7] (El ϭ Br; 49%), 3c[7,8]
(El ϭ I; 3%) and the presumed, though not unequivocally
characterized, 3d (El ϭ OH; 30%), along with the disubsti-
tuted products 2b[7,9Ϫ11] (El ϭ Br; 31%), 2c[12] (El ϭ I;
60%), and 2d (El ϭ OH; 38%), to radical-generating pro-
As previously reported, benzene[1] and other arenes[2] un-
dergo double metalation if exposed to the superbasic mix-
ture of butyllithium and potassium tert-butoxide in hexanes
or other paraffinic solvents. In the same context, the tert-
butyl group was found to severely inhibit deprotonation at
neighboring positions as long as other sites remain
available.[1Ϫ3] This not being the case with 1,4-di-tert-butyl-
benzene, its mono- and dimetalation can be brought about
only at elevated temperatures (ϩ75 °C for 24 h) and with
poor yields.[2] In contrast, tert-butylbenzene reacts
smoothly at ambient temperature to provide meta- and
para-mono- and meta,metaЈ-disubstituted derivatives in
80Ϫ90% total yields depending on the stoichiometry.[2] If
an excess of the superbase is employed, 4,4Ј-di-tert-butylbi-
phenyl, a paraϪpara coupled ‘‘dimer’’ of tert-butylbenzene,
should consequently be exclusively and efficaciously at-
tacked at the 2- and 2Ј-position. This prediction proved to
be correct.
4,4Ј-Di-tert-butylbenzene, a commercial product, was
dissolved in hexanes and treated for 12 h at ϩ70 °C with
two molar equivalents of butyllithium and potassium tert-
butoxide before the reaction was quenched with dichlorodi-
methylsilane to afford the 2,7-di-tert-butyl-9,9-dimethyl-9-
silafluorene[4] (1; 72%). Trapping of the intermediate with
carbon dioxide followed by neutralization gave 2,2Ј-biphen-
yldicarboxylic acid[5] (2a; 53%) and 2,7-di-tert-butylfluor-
[a]
´
Institut de Chimie moleculaire et biologique, Ecole
´ ´
Polytechnique Federale, BCh,
1015 Lausanne, Switzerland
E-mail: manfred.schlosser@epfl.ch
Faculte des Sciences, Universite, BCh,
[b]
[‡]
´
´
1015 Lausanne, Switzerland
´ ´
New address: Laboratoire de stereochimie,
´
Universite Pasteur (ECPM)
67087 Strasbourg, France
1014
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300630
Eur. J. Org. Chem. 2004, 1014Ϫ1017

Superbase-Mediated Pairwise Substitution in a Biphenyl Derivative
FULL PAPER
cesses unleashed in the moment of reaction with, respec- presence of sodium iodide to yield the dimethyl derivative
tively, bromine, iodine and fluorodimethoxyborane (in the 9 (78%). Removal of the tert-butyl groups with aluminum
latter case followed by oxidation with hydrogen peroxide). trichloride provided 6,6Ј-dimethylbiphenyl-2,2Ј-diol (10;
The bisphenol was quantitatively converted into the di- 89%), a known substance.[13]
methoxy compound 2e (97%).
A first attempt to introduce a second pair of substituents
Experimental Section
into the 6,6Ј-positions failed. Despite the steric hindrance
caused by the bulky tert-butyl groups, iodination of the
2,2Ј-dimethoxybiphenyl 2e occurred selectively at the 5,5Ј-
positions with no effect on the 6- or 6Ј-positions. When the
resulting diiodo derivative 5 (80%) was consecutively sub-
jected to halogen/metal permutation and carboxylation, the
diacid 6 was produced in 95% yield.
General: For laboratory routine and abbreviations, see recent
publications[14Ϫ16] from this laboratory. 1H and (1H-decoupled) 13
C
NMR spectra were recorded at 400 and 101 MHz, respectively. The
samples were dissolved in deuteriochloroform unless stated other-
wise. As the intensities of 13C signals cannot be exactly measured,
they are visually estimated. The signal intensities given (e.g.,
2:2:2:18:6 rather than 1:1:1:9:3 H ratios) take into account the mass
spectrometric information. To avoid redundancy, only [79Br] frag-
ments and no [81Br] isotopomers are listed in the mass spectra.
2,7-Di-tert-butyl-9,9-dimethyl-9H-9-silafluorene (1): Potassium tert-
butoxide (11 g, 0.10 mol) was added to a solution of butyllithium
(0.10 mol) and 4,4Ј-di-tert-butylbiphenyl (13 g, 50 mmol) in hex-
anes (60 mL). The suspension was stirred for 12 h at 70 °C. At Ϫ75
°C, the mixture was treated with dichlorodimethylsilane (12 mL,
13 g, 0.10 mol) before being evaporated. The residue was crys-
tallized from pentanes to give colorless cubes; yield: 11.6 g (72%);
1
m.p. 166Ϫ167 °C (ref.[4] m.p. 167 °C). H NMR (ppm): δ ϭ 7.71
(d, J ϭ 8.0 Hz, 2 H), 7.63 (d, J ϭ 2.0 Hz, 2 H), 7.45 (dd, J ϭ 8.0,
2.0 Hz, 2 H), 1.37 (s, 18 H), 0.43 (s, 6 H). 13C NMR (ppm): δ ϭ
149.8 (2 C), 145.7 (2 C), 139.0 (2 C), 129.6 (2 C), 127.5 (2 C), 120.0
(2 C), 35.0 (2 C), 31.5 (6 C), 3.0 (2 C). MS (c.i.): m/z (%) ϭ 340 (9)
[Mϩ ϩ NH3], 322 (49) [Mϩ], 307 (100), 267 (10), 235 (6). C22H30Si
(322.57): calcd. C 81.92, H 9.37; found C 81.87, H 9.27.
The objective of introducing functional substituents pair-
wise in the 2,2Ј- and 6,6Ј-positions was realized by the su-
perbase-promoted metalation of the bisphenolate obtained
by deprotonation of the dihydroxy compound 2d. Upon
carboxylation and neutralization, the bislactone 7 was iso-
lated in 41% yield. It was first reduced with aluminum hy-
dride to the bis(hydroxymethyl) compound 8 (63%) and
subsequently treated with chlorotrimethylsilane in the
4,4Ј-Di-tert-butylbiphenyl-2,2Ј-dicarboxylic Acid (2a): A mixture
(see above) formed by the reaction of 4,4Ј-di-tert-butylbiphenyl
(13 g, 50 mmol) with butyllithium (0.10 mol) and potassium tert-
butoxide (11 g, 0.10 mol) was poured onto an excess of freshly
crushed dry ice covered by a layer of tetrahydrofuran. At 25 °C,
it was extracted with a 10% aqueous solution (50 mL) of sodium
hydroxide. The aqueous phase was washed with diethyl ether (3 ϫ
20 mL) and acidified to pH 5. The solid precipitate was collected
by filtration and crystallized from 50% aqueous ethanol to afford
colorless needles; yield: 9.39 g (53%); m.p. 300Ϫ301 °C (reprod.;
ref.[5] m.p. 301Ϫ304 °C). 1H NMR (ppm): δ ϭ 7.61 (d, J ϭ 2.0 Hz,
2 H), 7.43 (t, J ϭ 2.0 Hz, 2 H), 7.41 (d, J ϭ 2.0 Hz, 2 H), 1.35
(s, 18 H). MS: m/z (%) ϭ 354 (61) [Mϩ], 330 (100), 280 (12), 174
(3), 120 (6).
4,4Ј-Di-tert-butyl-2,2Ј-dibromobiphenyl (2b): This was obtained
analogously (see above) after treatment of 4,4Ј-di-tert-butylbi-
phenyl (13 g, 50 mmol) with a solution of bromine (5.1 mL, 16 g,
0.10 mol) in hexanes (50 mL) which was added dropwise over the
course of 15 min. At 25 °C, the organic phase was washed with an
aqueous solution (0.10 L) of sodium sulfite (5.0 g) and the solvents
evaporated. The residue was crystallized from ethanol to afford
colorless needles; yield: 15.0 g (36%); m.p. 160Ϫ161 °C (ref.[6] m.p.
157Ϫ158 °C). 1H NMR (ppm): δ ϭ 7.90 (d, J ϭ 2.0 Hz, 2 H), 7.40
(dd, J ϭ 8.0, 2.0 Hz, 2 H), 7.10 (d, J ϭ 8.0 Hz, 2 H), 1.35 (s, 18
H). MS: m/z (%) ϭ 422 (40) [Mϩ], 345 (100), 310 (60), 214 (12),
134 (23), 112 (12).
4,4Ј-Di-tert-butyl-2,2Ј-diiodobiphenyl (2c): This was obtained anal-
ogously (see above) after treatment of 4,4Ј-di-tert-butylbiphenyl
(13 g, 50 mmol) with elemental iodine (26 g, 0.10 mol) with vigor-
ous stirring. At 25 °C, the organic phase was washed with an aque-
Eur. J. Org. Chem. 2004, 1014Ϫ1017
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1015

M. Schlosser, G. Mangano, F. Leroux
ous solution (0.10 L) of sodium sulfite (5.0 g) and the solvents 2-Bromo-4,4Ј-di-tert-butylbiphenyl (3b) and 4,4Ј-di-tert-butyl-2-
FULL PAPER
evaporated under reduced pressure. The residue was crystallized
iodobiphenyl (3c), formed as by-products along with the 2,2Ј-disub-
stituted analogs 2b and 2c, were equally identified by gas chromato-
from ethanol to afford colorless needles; yield: 31.0 g (60%); m.p.
1
140Ϫ141 °C (ref.[6] m.p. 140Ϫ141 °C). H NMR (ppm): δ ϭ 7.90 graphic comparison of their retention times with those of authentic
(d, J ϭ 2.0 Hz, 2 H), 7.40 (dd, J ϭ 8.0, 2.0 Hz, 2 H), 7.10 (d, J ϭ
8.0 Hz, 2 H), 1.35 (s, 18 H). MS (c.i.): m/z (%) ϭ 536 (51) [M ϩ
NH4ϩ], 518 (100) [Mϩ], 513 (87), 512 (88), 345 (23), 312 (12), 245
(3), 124 (10).
samples[7] (2 m, 5% C-20M, 120 °C; 30 m, DB-1, 100 °C).
4,4Ј-Di-tert-butyl-2-hydroxybiphenyl (3d): The mother liquor from
which the main product 4,4Ј-di-tert-butylbiphenyl-2,2Ј-diol (2d; see
above) had been removed by crystallization was evaporated and the
residue was crystallized from methanol to afford colorless needles;
yield: 4.24 g (30%); m.p. 113Ϫ114 °C. 1H NMR (ppm): δ ϭ 7.5
(m, 2 H), 7.3 (m, 2 H), 7.14 (d, J ϭ 7.2 Hz, 1 H), 7.03 (dd, J ϭ
7.5, 2.0 Hz, 1 H), 6.77 (d, J ϭ 2.0 Hz, 1 H), 1.29 (s, 9 H), 1.23 (s,
9 H). 13C NMR (ppm): δ ϭ 155.5, 147.1, 146.3, 133.2, 131.3, 128.1,
127.2 (2 C), 125.3 (2 C), 118.3, 113.0, 35.2, 34.9, 31.5 (6 C). MS:
m/z (%) ϭ 282 (23) [Mϩ], 220 (100), 187 (56), 151 (41), 123 (14),
108 (3).
4,4Ј-Di-tert-butylbiphenyl-2,2Ј-diol (2d): At Ϫ75 °C, a mixture
formed (see above) by the reaction of 4,4Ј-di-tert-butylbiphenyl
(13 g, 50 mmol) with butyllithium (0.10 mol) and potassium tert-
butoxide (11 g, 0.10 mol) was treated with the fluorodimethoxybor-
ane diethyl ether 1:1 complex[17,18] (19 mL, 17 g, 0.10 mol), which
was added dropwise over 1 h. At 25 °C, sodium hydroxide pellets
(2.0 g, 50 mmol) and 30% hydrogen peroxide solution (10 mL,
0.10 mmol) were added. The mixture was stirred for 2 h at 25 °C
before being acidified to pH 5. The organic phase was decanted
and the aqueous phase was extracted with diethyl ether (3 ϫ
20 mL). The combined organic layers were dried and the solvents
evaporated. The residue was crystallized from heptanes to afford
2,7-Di-tert-butylfluoren-9-one (4): This compound was isolated as
a by-product from the reaction in which di-tert-butylbiphenyl was
mainly converted into the diacid 2a (see above). After alkaline ex-
traction, the organic solution was evaporated and the residue crys-
tallized from pentanes to afford yellow platelets; yield: 2.19 g
(15%); m.p. 111Ϫ112 °C (ref.[6] m.p. 109Ϫ110 °C). 1H NMR (ppm):
δ ϭ 7.6 (m, 3 H), 7.1 (m, 3 H), 1.33 (s, 18 H). MS: m/z (%) ϭ 292
(12) [Mϩ], 287 (34), 210 (100), 167 (1), 156 (3), 123 (5).
1
colorless needles; yield: 5.67 g (38%); m.p. 190Ϫ191 °C. H NMR
(ppm): δ ϭ 7.2 (m, 2 H), 7.1 (m, 4 H), 1.34 (s, 18 H). 13C NMR
(ppm): δ ϭ 154.2 (2 C), 151.0 (2 C), 131.5 (2 C), 123.2 (2 C), 116.0
(2 C), 113.0 (2 C), 34.2 (2 C), 31.5 (6 C). MS (c.i.): m/z (%) ϭ 316
(38) [M ϩ NH4ϩ], 300 (32), [Mϩ ϩ 2], 299 (100) [Mϩ ϩ 1], 298
(93) [Mϩ]. C20H26O2 (298.43): calcd. C 80.50, H 8.78; found C
80.83, H 8.49.
4,4Ј-Di-tert-butyl-5,5Ј-diiodo-2,2Ј-dimethoxybiphenyl (5):
A bi-
phasic mixture composed of 4,4Ј-di-tert-butyl-2,2Ј-dimethoxybi-
phenyl (16 g, 50 mmol), periodic acid dihydrate (2.3 g, 10 mmol),
iodine (51 g, 0.20 mol), 98% sulfuric acid (1.0 mL), glacial acetic
acid (26 mL), tetrachloromethane (20 mL), and water (4.5 mL) was
heated to 80 °C for 2 h before being poured into a saturated solu-
tion (0.20 L) of sodium sulfite. The aqueous phase was extracted
with diethyl ether (3 ϫ 20 mL). The combined organic phases were
dried and the solvents evaporated under reduced pressure. The resi-
due was crystallized from ethanol to afford white cubes; yield:
23.1 g (80%); m.p. 120Ϫ121 °C. 1H NMR (ppm): δ ϭ 7.78 (s, 2 H),
7.04 (s, 2 H), 3.77 (s, 6 H), 1.57 (s, 18 H). 13C NMR (ppm): δ ϭ
157.0 (2 C), 151.0 (2 C), 145.5 (2 C), 125.5 (2 C), 111.5 (2 C), 82.8
(2 C), 55.9 (2 C), 37.0 (2 C), 29.9 (6 C). MS: m/z (%) ϭ 578 (79)
[Mϩ ϩ 1], 452 (100), 326 (53), 215 (5), 128 (6). C22H28I2O2 (578.26):
calcd. C 45.70, H 4.88; found C 45.64, H 4.90.
4,4Ј-Di-tert-butyl-2,2Ј-dimethoxybiphenyl (2e): A slurry of pot-
assium hydride (0.8 g, 20 mmol) in a solution of 4,4Ј-di-tert-butyl-
biphenyl-2,2Ј-diol (2d; 3.0 g, 10 mmol) and methyl iodide (1.2 mL,
2.7 g, 20 mmol) in tetrahydrofuran (50 mL) was stirred for 2 h at
25 °C. Upon evaporation of the volatiles a white solid was ob-
tained, which was crystallized from 50% aqueous ethanol to afford
colorless platelets; yield: 3.17 g (97%); m.p. 142Ϫ143 °C. 1H NMR
(ppm): δ ϭ 7.2 (s, 2 H), 7.0 (m, 4 H), 3.79 (s, 6 H), 1.36 (s, 18 H).
13C NMR (ppm): δ ϭ 157.0 (2 C), 152.0 (2 C), 131.5 (2 C), 125.0
(2 C), 117.8 (2 C), 109.0 (2 C), 56.0 (2 C), 35.0 (2 C), 31.7 (6 C).
MS: m/z (%) ϭ 328 (12) [Mϩ ϩ 2], 327 (56) [Mϩ ϩ 1], 326 (100)
[Mϩ], 311 (85). C22H30O2 (326.47): calcd. C 80.9, H 9.26; found C
81.03, H 9.19.
4,4Ј-Di-tert-butylbiphenyl-2-carboxylic Acid (3a): At Ϫ75 °C 4,4Ј-
di-tert-butyl-2-iodobiphenyl[7] (3c; 7.8 g, 20 mmol) in tetrahydrofu-
ran (50 mL) was added to tert-butyllithium (40 mmol) in hexanes
(25 mL). The mixture was poured, 5 min later, onto an excess of
freshly crushed dry ice covered by a layer of tetrahydrofuran. The
product was isolated as described above (see diacid 2a) to afford
colorless needles (from 50% aqueous ethanol); yield: 5.28 g (85%);
m.p. 221Ϫ222 °C (reprod.). 1H NMR (ppm): δ ϭ 7.94 (d, J ϭ
2.1 Hz, 1 H), 7.55 (dd, J ϭ 8.1, 2.1 Hz, 1 H), 7.38 (d, J ϭ 8.1 Hz,
2 H), 7.30 (d, J ϭ 8.1 Hz, 1 H), 7.27 (d, J ϭ 8.1 Hz, 2 H), 1.36 (s,
9 H), 1.34 (s, 9 H). 13C NMR (ppm): δ ϭ 174.3, 150.0, 140.3, 137.8,
132.3, 131.1, 129.1, 128.9, 128.2, 127.5 (2 C), 125.0 (2 C), 34.6,
34.5, 31.4 (3 C), 31.2 (3 C). MS: m/z (%) ϭ 310 (22) [Mϩ], 295
(100) 237 (6), 178 (3), 112 (3). C21H26O2 (310.43): calcd. C 81.25,
H 8.44; found C 81.48, H 8.11.
4,4Ј-Di-tert-butyl-6,6Ј-dimethoxybiphenyl-3,3Ј-dicarboxylic
Acid
(6): At Ϫ75 °C, tert-butyllithium (80 mmol) in pentanes (54 mL)
was added to 4,4Ј-di-tert-butyl-5,5Ј-diiodo-2,2Ј-dimethoxybiphenyl
5 (12 g, 20 mmol) in tetrahydrofuran (40 mL). After 5 min the mix-
ture was poured onto an excess of freshly crushed dry ice covered
by a layer of tetrahydrofuran. The product was isolated as de-
scribed for diacid 2a to afford colorless needles (from 50% aqueous
ethanol); yield: 7.88 g (95%); m.p. 210Ϫ211 °C (reprod.). 1H NMR
(D3CSOCD3, ppm): δ ϭ 7.20 (s, 2 H), 7.22 (s, 2 H), 3.89 (s, 6 H),
1.57 (s, 18 H). 13C NMR (D3CSOCD3, ppm): δ ϭ 174.2 (2 C),
158.5 (2 C), 149.8 (2 C), 132.6 (2 C), 127.7 (2 C), 124.5 (2 C), 101.1
(2 C), 56.7 (2 C), 37.1 (2 C), 32.1 (6 C). MS: m/z (%) ϭ 414 (1)
[Mϩ], 215 (1), 84 (100). C24H30O6 (414.50): calcd. C 69.55, H 7.30;
found C 69.51, H 7.33.
2,7-Di-tert-butyl-5,10-dihydro-[1]benzopyrano[5,4,3-cde][1]benzo-
pyran-5,10-dione (7): At Ϫ75 °C, potassium tert-butoxide (9.0 g,
This acid was converted into its methyl ester by exhaustive treat-
ment with ethereal diazomethane. The crude reaction mixture from 80 mmol) and 4,4Ј-di-tert-butylbiphenyl-2,2Ј-diol (2d; 3.3 g,
which diacid 2a was isolated (see above) was esterified in the same
manner and examined by gas chromatography (2 m, 5% C-20M,
120 °C; 30 m, DB-1, 100 °C). Not even trace amounts (Ͻ 3%) of
the monoester were detected by comparison of the retention times.
10 mmol) were added to butyllithium (80 mmol) in hexanes
(50 mL). The suspension was stirred at 70 °C for 6 h. After cooling
to 25 °C, the mixture was poured onto an excess of freshly crushed
dry ice covered with a layer of tetrahydrofuran. A 10% aqueous
1016
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1014Ϫ1017

Superbase-Mediated Pairwise Substitution in a Biphenyl Derivative
FULL PAPER
solution (50 mL) of sodium hydroxide was then added and the
aqueous phase was washed with diethyl ether (3 ϫ 20 mL) before
being acidified to pH 5 and extracted with ethyl acetate (3 ϫ
20 mL). The organic layer was dried and the volatiles were evapo-
rated. The residue was crystallized from a 1:1 (v/v) ethyl acetate/
pentane mixture to afford white platelets; yield: 1.44 g (41%); m.p.
190Ϫ191 °C. 1H NMR (ppm): δ ϭ 8.23 (s, 2 H), 7.75 (s, 2 H), 1.44
(s, 18 H). 13C NMR (ppm): δ ϭ 173.3 (2 C), 159.9 (2 C), 156.2 (2
2,2Ј-Dihydroxy-6,6Ј-dimethylbiphenyl (10): A suspension of alumi-
num trichloride (2.0 g, 15 mmol) and 4,4Ј-di-tert-butyl-6,6Ј-dimeth-
ylbiphenyl-2,2Ј-diol (9; 1.6 g, 5.0 mmol) in benzene (89 mL, 78 g,
1.0 mol) was stirred at 25 °C for 20 h. After the addition of 10%
hydrochloric acid (0.10 L) the stirring was continued for an ad-
ditional 10 min before the organic layer was decanted and the aque-
ous phase was extracted with ethyl acetate (3 ϫ 20 mL). The vol-
atiles were evaporated and the residue was crystallized from meth-
C), 149.7 (2 C), 119.5 (2 C), 115.5 (2 C), 112.5 (2 C), 36.0 (2 C), anol to afford colorless platelets; yield: 0.95 g (89%); m.p. 160Ϫ161
1
31.5 (6 C). MS: m/z (%) ϭ 350 (34) [Mϩ], 263 (100), 222 (37), 180
°C (ref.[13] m.p. 161.0Ϫ162.5 °C). H NMR (ppm): δ ϭ 7.2 (m, 2
(3), 165 (5), 138 (2). C22H22O4 (350.41): calcd. C 75.41, H 6.33; H), 6.9 (m, 4 H), 2.01 (s, 6 H). 13C NMR (ppm): δ ϭ 154.0 (2 C),
found C 75.39, H 6.25.
139.1 (2 C), 130.0 (2 C), 122.8 (2 C), 119.9 (2 C), 113.4 (2 C), 19.5
(2 C). MS: m/z (%) ϭ 214 (100) [Mϩ], 201 (32), 156 (12), 120 (2),
96 (12).
4,4Ј-Di-tert-butyl-6,6Ј-bis(hydroxymethyl)biphenyl-2,2Ј-diol (8):
A
suspension of bislactone 7 (3.9 g, 10 mmol), aluminum trichloride
(2.7 g, 20 mmol), and lithium aluminum hydride (0.8 g, 20 mmol)
in diethyl ether (0.10 L) was stirred at 35 °C for 20 h. A saturated
aqueous solution (50 mL) of sodium sulfate was added dropwise
over 15 min followed by 10% hydrochloric acid (50 mL). The mix-
ture was stirred for 1 h at 25 °C and filtered through a pad of
diatomaceous earth. The filter cake was washed with ethyl acetate
(5 ϫ 20 mL). The white solid obtained after evaporation of the
volatiles was crystallized from a 1:1 (v/v) ethyl acetate/pentane mix-
ture to afford colorless needles; yield: 2.26 g (63%); m.p. 249Ϫ250
Acknowledgments
This work was financially supported by the Schweizerische National-
fonds zur Förderung der wissenschaftlichen Forschung, Bern (grant
20-55Ј303-98) and the Bundesamt für Bildung und Wissenschaft,
Bern (grant 97.0083 linked to the TMR project FMRXCT-970129).
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[3]
E. Baston, Q. Wang, M. Schlosser, Tetrahedron Lett. 2000,
6.79 (s, d, J ϭ 1.4 Hz, 2 H), 4.13 (d, J ϭ 14.5 Hz, 2 H), 3.97 (d,
J ϭ 14.5 Hz, 2 H), 1.30 (s, 18 H). 13C NMR (ppm): δ ϭ 153.2 (2
C), 149.5 (2 C), 141.2 (2 C), 118.1 (2 C), 114.0 (2 C), 110.8 (2 C),
41, 667Ϫ670.
[4]
M. Ishikawa, T. Tabohashi, H. Sugisawa, K. Nishimura, M.
Kumada, J. Organomet. Chem. 1983, 250, 109Ϫ119.
61.1 (2 C), 34.2 (2 C), 31.2 (6 C). MS: m/z (%) ϭ 359 (70) [Mϩ
ϩ
[5]
´
´
E. Balogh-Hergovich, G. Speier, Z. Tyeklar, Synthesis 1982,
1], 358 (30) [Mϩ], 291 (100), 220 (32), 218 (1), 156 (12), 120 (3).
C22H30O4 (358.47): calcd. C 73.71, H 8.44; found C 73.94, H 8.03.
731Ϫ732.
[6]
M. Bruch, M. Große, D. Rewicki, Justus Liebigs Ann. Chem.
1976, 74Ϫ88.
M. Tashiro, T. Yamato, J. Org. Chem. 1979, 44, 3037Ϫ3041.
T. Umemoto, S. Ishihara, J. Am. Chem. Soc. 1993, 115,
2156Ϫ2164.
J. Y. Corey, L. S. Chang, J. Organomet. Chem. 1986, 307, 7Ϫ14.
R. Hohenadel, H.-A. Brune, J. Organomet. Chem. 1988, 350,
101Ϫ108.
L. S. Chang, J. Y. Corey, Organometallics 1989, 8, 1885Ϫ1893.
H. G. Alt, R. Zenk, J. Organomet. Chem. 1996, 512, 51Ϫ60.
H. Suda, M. Motoi, N. Tamura, S. Kanoh, Bull. Chem. Soc.
Jpn. 1987, 60, 2307Ϫ2309.
O. Desponds, C. Huynh, M. Schlosser, Synthesis 1998,
983Ϫ985.
C. Bobbio, M. Schlosser, Eur. J. Org. Chem. 2001, 4533Ϫ4536.
M. Schlosser, M. Marull, Eur. J. Org. Chem. 2003, 1569Ϫ1575.
G. Rauchschwalbe, M. Schlosser, Helv. Chim. Acta 1975, 58,
1094Ϫ1099.
[7]
[8]
4,4Ј-Di-tert-butyl-6,6Ј-dimethylbiphenyl-2,2Ј-diol (9):
A hetero-
geneous mixture of 6,6Ј-bis(hydroxymethyl)-4,4Ј-di-tert-butylbiphe-
nyl-2,2Ј-diol (8; 2.4 g, 5.0 mmol), chlorotrimethylsilane (6.3 mL,
5.4 g, 50 mmol), and sodium iodide (7.5 g, 50 mmol) in dry aceto-
nitrile (20 mL) was stirred at 25 °C for 20 h before being poured
into a 10% aqueous solution (50 mL) of sodium sulfite. The aque-
ous phase was extracted with ethyl acetate (3 ϫ 20 mL) and the
combined organic phases evaporated. The residue was crystallized
from pentanes to afford colorless cubes; yield: 1.27 g (78%); m.p.
182Ϫ183 °C. 1H NMR (ppm): δ ϭ 7.01 (s, 2 H), 6.91 (s, 2 H), 2.01
(s, 6 H), 1.33 (s, 18 H); integrals in the ratio of 1.0:1.0:3.0:9.0. 13C
NMR (ppm): δ ϭ 154.0 (2 C), 151.3 (2 C), 147.4 (2 C), 127.0 (2
C), 124.5 (2 C), 116.0 (2 C), 35.0 (2 C), 31.0 (2 C), 20.1 (6 C). MS
(c.i.): m/z (%) ϭ 344 (5) [M ϩ NH4ϩ], 327 (17) [Mϩ ϩ 1], 326 (22)
[Mϩ], 325 (61) [Mϩ Ϫ 1], 324 (100) [Mϩ Ϫ 2], 323 (93), 322 (61),
321 (17). C22H30O2 (326.48): calcd. C 80.93, H 9.26; found C 81.04,
H 9.29.
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
M. Schlosser, L. Franzini, Synthesis 1998, 707Ϫ709, spec. foot-
note (14).
Received October 8, 2003
Eur. J. Org. Chem. 2004, 1014Ϫ1017
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1017