A modified in situ Suzuki cross-coupling of haloarenes for the preparation of C2-symmetric biaryls

Full text of DOI:10.1021/jo9617880

9556
J . Org. Chem. 1996, 61, 9556-9559
Sch em e 1
A Mod ified in Situ Su zu k i Cr oss-Cou p lin g
of Ha loa r en es for th e P r ep a r a tion of
C2-Sym m etr ic Bia r yls
Neil G. Andersen, Shawn P. Maddaford, and
Brian A. Keay*
Department of Chemistry, University of Calgary, Calgary,
Alberta, Canada T2N 1N4
Ta ble 1. In itia l Attem p ts to P r ep a r e C2-Sym m etr ic
Bia r yls via th e in Situ Su zu k i Rea ction
Received August 19, 1996
entrya
halide
base
product (% yield)b
Palladium-catalyzed cross-coupling between aryl bo-
ronic acids and haloarenes or aryl triflates has been
shown to be a versatile method for the preparation of
biaryls.1 The original procedure developed by Suzuki2
has achieved widespread popularity in organic synthesis
since it is compatible with a large variety of functional
groups and the conditions tolerate aqueous reaction
media. Moreover, the inorganic byproduct of the reaction
is nontoxic and easily removed from the reaction mixture
thereby making the Suzuki protocol suitable for indus-
trial processes. Moreno-Man˜as et al.3 have recently
reported a palladium-catalyzed Suzuki type self-coupling
of arylboronic acids for the preparation of symmetrical
biaryls. The initial findings for this method are promis-
ing; however, the versatility of the reaction with respect
to various functional groups and the effect of steric
hinderance at the ortho positions has not been fully
investigated. Moreover, the self-coupling method re-
quires the isolation of the organoboronic acid precursor.
Although these compounds are generally quite thermally
stable and not air-sensitive, their high solubility in
aqueous media often complicates their isolation and
purification procedures. We have recently reported an
efficient method for the cross-coupling of aryl, furyl,
primary, and benzylic boranes with aryl or vinyl bromides
and iodides without the need for isolation of the orga-
noboronic acid.4 We herein report a method for the
preparation of C2-symmetric biaryls via a modified in situ
Suzuki cross-coupling reaction.5
1
2
3
4
iodobenzene
iodobenzene
bromobenzene
2-bromotoluene
2 M Na2CO3 biphenyl (73)
Ba(OH)2
Ba(OH)2
biphenyl (80)
biphenyl (85)
2 M Na2CO3 2,2′-dimethyl-
biphenyl (40)
5
6
2-bromoanisole
Ba(OH)2
2,2′-dimethoxy-
biphenyl (56)
1-iodo-2-methoxy- 2 M Na2CO3 2,2′-dimethoxy-1,1′-
naphthalene binaphthyl (<10)
a
All reactions done in toluene with Pd(PPh3)4 and 12 h reflux
b
time. Isolated yields.
substituents afforded the respective biaryls in disap-
pointing yield (Table 1). Suzuki and co-workers have
demonstrated that the cross-coupling of sterically hin-
dered boronic acids with haloarenes is greatly enhanced
by use of stronger bases such as Ba(OH)2, NaOH, and
TlOH.6 In our hands, use of a saturated aqueous solution
of Ba(OH)2 in place of the 2 M Na2CO3 had little effect
on the reaction outcome. When 1-iodo-2-methoxynaph-
thalene (entry 6) was treated under our initial reaction
conditions, less than 10% of the desired binaphthyl
product was formed. The remainder of the reaction
mixture was determined to be a 2:1:1 mixture of the
starting haloarene, 2-methoxy-1-naphthylboronic acid,
and 2-methoxynaphthalene, respectively. Increasing the
reaction time did not significantly increase the yield of
the desired binaphthyl but rather resulted in increased
amounts of the hydrolytic deboration product, 2-meth-
oxynaphthalene, being isolated from the reaction mix-
ture.
In order to optimize the reaction conditions, we decided
to investigate the role of different solvent mixtures on
the in situ cross-coupling of 1-iodo-2-methoxynaphtha-
lene. We were pleased to find that the 3:3:1 mixture of
toluene, ethanol, and water reported by Grahn et al.7
afforded a 96% yield of the desired binaphthyl (5b) (Table
2, entry 12). This solvent mixture was not limited to this
one example, and Table 2 summarizes the scope and
limitations of the optimized reaction conditions. In
general, the developed in situ method affords C2-sym-
metric biaryls in moderate to excellent yield and tolerates
a wide range of functionalities including esters, amides,
acetals, and nitriles (entries 6-9, respectively). The
reaction was limited by the presence of a phenolic TBDPS
group which was cleaved under the reaction conditions
(entry 10).
Our interests in natural product synthesis and chiral
auxiliary design prompted us to develop an in situ Suzuki
coupling method for synthesizing C2-symmetric biaryls
which obviates the need for boronic acid isolation. By
treating the starting haloarene with only 0.5 equiv of
n-butyllithium followed by an excess of trimethoxyborate,
we felt that it would be possible to generate the needed
1:1 molar ratio of haloarene and arylboronic acid in situ
which could subsequently be coupled under modified
Suzuki conditions (Scheme 1).
Treatment of a solution of iodobenzene in THF under
the above conditions afforded biphenyl in 73% yield.
Unfortunately, haloarenes possessing one or more ortho
(1) For a recent review, see: Suzuki, A.; Miyaura, N. Chem. Rev.
1995, 95, 2457.
(2) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981,
11, 513. (b) Hoshino, Y.; Miyaura, N.; Suzuki, A. Bull. Chem. Soc. J pn.
1988, 61, 3008. (c) Satoh, M.; Miyaura, N.; Suzuki, A. Chem Lett. 1989,
1405. (d) Suzuki, A. Pure Appl. Chem. 1991, 63, 419.
(3) Moreno-Man˜as, M.; Pe´rez, M.; Pleixats, R. J . Org. Chem. 1996,
61, 2346.
(4) (a) Maddaford, S. P.; Keay, B. A. J . Org. Chem. 1994, 59, 6501.
(b) Cristofoli, W. A.; Keay, B. A. Tetrahedron Lett. 1991, 32, 5881. (c)
Cristofoli, W. A.; Keay, B. A. Synlett 1994, 625.
The synthetic value of this method could be realized
for the production of many C2-symmetric biaryls needed
for chiral ligand development and natural product syn-
thesis. To demonstrate the latter, we endeavored to
synthesize the recently discovered 4,4′-dihydroxy-5,5′-
(5) Formation of organometallic nucleophiles in situ for the prepara-
tion of biaryls has previously been demonstrated intramolecularly for
the synthesis of phenanthrenes; see: Kelly, T. R.; Li, Q.; Bhushan, V.
Tetrahedron Lett. 1990, 31, 161.
(6) (a) Suzuki, A. Pure Appl. Chem. 1994, 66, 213. (b) Watanabe,
T.; Miyaura, N.; Suzuki, A. Synlett 1992, 207.
(7) Grahn, W.; et al. Angew. Chem., Int. Ed. Engl. 1995, 34, 1485.
S0022-3263(96)01788-4 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 26, 1996 9557
Sch em e 2a
Ta ble 2. Resu lts fr om th e P r ep a r a tion of C2-Sym m etr ic
Bia r yls Usin g th e Op tim ized in Situ Su zu k i Cou p lin g
Con d ition s
product
product
entry
halide
(% Yield)a
entry
halide
(% Yield)a
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
4a (85)
4b (73)
4c (79)
4d (95)
4e (89)
4f (32)
4g (79)
8
9
1h
1i
1j
2a
2b
2c
3
4h (91)
4i (68)
4j (92)b
5a (86)
5b (96)
5c (84)
6 (73)
10
11
12
13
14
1g
a
b
Isolated yield. Hydrolysis of the TBDPS ether takes place
under the reaction conditions.
a
(a) 1 equiv of NaH, DMF, 5 equiv of MeI (95%); (b) NaH, CCl4,
1 equiv of Br2 (60%); (c) NaH, DMF, BnBr, (100%); (d) 0.5 equiv
of n-BuLi, THF -78 °C then B(OMe)3 rt 12 h and then PhCH3,
EtOH, H2O, Na2CO3, Pd(PPh3)4 reflux 12 h (72%); (e) H2, Pd/C,
EtOH/CH2Cl2 (100%).
group in 9 with benzyl bromide in DMF and subsequent
treatment of the resulting benzyl ether with our modified
in situ Suzuki coupling protocol afforded coupled product
11 in 72% yield. Removal of the benzyl groups via
hydrogenolysis yielded the natural product 12 in an
overall yield of 41% (five steps).
In summary, we have developed a one step modified
in situ Suzuki coupling method for the production of C2-
symmetric biaryls which eliminates the need for boronic
acid isolation. Moderate to excellent yields are obtained
and a wide variety of functional groups are tolerated.
Moreover, our in situ method is synthetically useful for
the synthesis of natural products and the preparation of
C2-symmetric biaryl ligands.
Exp er im en ta l Section
Gen er a l Com m en ts. All reactions were conducted under an
atmosphere of nitrogen in oven-dried glassware with magnetic
stirring. All chemicals were reagent grade and used without
purification. Ether refers to diethyl ether. THF was distilled
from Na/benzophenone ketyl immediately prior to use. Merck
silica gel 60 (230-400 mesh) was used for chromatography,
which was carried out by using the flash technique.10 Radial
chromatography was accomplished using a model 7924T chro-
matotron. Thin-layer chromatography (TLC) was done on Merck
60F-254 silica gel plates. Detection of TLC components was
accomplished using either a 254/366 nm UV lamp or developing
with an acidic solution of (NH4)6Mo7O24‚4H2O. Melting points
are uncorrected. Elemental and MS analyses were performed
by D. Fox and Q. Wu at The University of Calgary. Starting
materials 1g,11 1h ,12 and 79 were synthesized according to
standard literature procedures with minor modification.
Gen er a l P r oced u r e for th e Cou p lin g of Ha loa r en es. To
a solution of the haloarene (1 mmol) in dry THF (10 mL) at -78
°C was added 0.5 equiv of n-BuLi followed by 1.5 equiv of
B(OMe)3. The resulting solution was warmed to rt over a 4 h
period and subsequently stirred overnight under an inert
atmosphere. To the solution were then added toluene (10 mL),
ethanol (10 mL), water (4 mL), Na2CO3 (1.5 mmol), and Pd-
(PPh3)4 (0.01 mmol). The resulting mixture was refluxed under
a N2 atmosphere for 24 h. The reaction contents were then
cooled to rt and extracted with CH2Cl2. The organic phases were
combined, washed with H2O, dried (MgSO4), filtered, and
concentrated in vacuo to afford the crude biaryl which was
dimethoxy-1,1′-binaphthyl (12) isolated from the fungus
(Ascomycetes) Daldinia concentrica8 (Scheme 2). 1,8-
Dihydroxynaphthalene (7) was chosen as a suitable
starting material and prepared from 1,8-naphthosultone
according to literature procedure.9 Monomethylation of
the starting diol under standard conditions gave methyl
ether 8 in 95% yield. The corresponding sodium phe-
noxide was brominated in CCl4 to afford a mixture of
regioisomers in which the desired bromide 9 was the
major component. Protection of the remaining hydroxyl
(10) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(11) (a) Szmuszkovicz, J . J . Org. Chem. 1964, 29, 843. (b) Stevens,
R. V.; Beaulieu, N.; Chan, W. H.; Daniewski, A. R.; Takeda, T.;
Waldner, A.; Williard, P. G.; Zutter, U. J . Am. Chem. Soc. 1986, 108,
1039.
(12) Crimmins, M. T.; DeLoach, A. J . Am. Chem. Soc. 1986, 108,
800.
(8) Hashimoto, T.; Tahara, S.; Takaoka, S.; Tori, M.; Askawa, Y.
Chem. Pharm. Bull. 1994, 42, 1528.
(9) (a) Lurie, A. P.; Brown, G. H.; Thirtle, J . R.; Weissberger, A. J .
Am. Chem. Soc. 1961, 83, 5015. (b) Hibbert, F.; Spiers, K. J . Chem.
Soc., Perkin Trans. 2 1988, 571.

9558 J . Org. Chem., Vol. 61, No. 26, 1996
Notes
further purified by a suitable method. Coupled products 4a ,b,13
4c,14 4d ,e,1 4h ,15 4i,16 4j,17 5a ,18 5b,19 5c,1 and 620 exhibited
spectral data and physical properties consistent to those reported
in the literature.
CDCl3) δ 4.04 (s, 3H), 7.22 (d, J ) 9.0 Hz, 1H), 7.39 (td, J ) 7.4
and 1.0 Hz, 1H), 7.56 (td, J ) 7.7 and 1.2 Hz, 1H), 7.75 (d, J )
7.8 Hz, 1H), 7.84 (d, J ) 9.0 Hz, 1H), 8.16 (d, J ) 8.5 Hz, 1H);
13C NMR (50 MHz, CDCl3) ppm 57.2 (q), 87.78 (s), 113.0 (d),
124.3 (d), 128.1 (d), 128.2 (d), 129.9 (s), 130.3 (d), 131.2 (d), 135.7
(s), 156.7 (s); MS (EI, m/ z) 284 (100, M+), 269 (14, M+ - CH3),
241 (45), 142 (69, M+ - CH3I).
Diisop r op yl 2,2′-bip h en yld ica r boxyla te (4f): mp 68-70
°C; IR (KBr) 1699, 1267, 1097 cm-1; 1H NMR (200 MHz, CDCl3)
δ 0.90 (d, 6H, J ) 6.2 Hz) 1.00 (d, 6H, J ) 6.2 Hz), 4.92 (sept,
2H, J ) 6.2 Hz), 7.19 (dd, 2H, J ) 4.0 and 1.3 Hz), 7.46 (m, 4H),
8.02 (dd, 2H, J ) 4.1 and 1.4 Hz); 13C NMR (50 MHz, CDCl3) δ
21.3, 67.9, 126.9, 129.9, 130.1, 130.4, 130.9, 143.3, 166.7; MS
(EI, m/ z) 197 (100, M+-C7H13O2), 239 (23, M+ - CO2C3H7), 326
(1, M+). HRMS calcd for C20H22O4 326.1518, found 326.1540;
Anal. Calcd for C20H22O4: C, 73.60; H, 6.79. Found: C, 73.60;
H, 6.80.
Isop r op yl 2-Iod oben zoa te (1f). To a solution of 2-iodoben-
zoic acid (2.49 g, 10.0 mmol) in DMF (80 mL) were added K2-
CO3 (3.47 g, 25.1 mmol) and isopropyl iodide (1.0 mL, 10.0
mmol). The resulting mixture was stirred at room temperature
for 24 h after which time the solution was diluted with ether
(300mL) and washed with 10% NaOH and brine. The organic
phase was dried (Na2SO4), filtered, and concentrated in vacuo
to afford an orange oil. The crude material was purified by
distillation under reduced pressure to give 2.76 g of 1f (95%):
bp 60-65 °C (0.1 mmHg); IR (neat) 1724, 1291, 1254, 1101, 1016
cm-1 1H NMR (200 MHz, CDCl3) δ 1.39 (d, J ) 6.2 Hz, 6H),
;
5.28 (sept, J ) 6.2 Hz, 1H), 7.14 (td, J ) 7.6 and 1.8 Hz, 1H),
7.4 (td, J ) 7.6 and 1.2 Hz, 1H), 7.76, (dd, J ) 7.7 and 1.7 Hz,
1H), 7.97 (dd, J ) 7.9 and 1.1 Hz, 1H); 13C NMR (50 MHz, CDCl3)
δ 21.8, 69.5, 93.8, 127.8, 130.6, 132.3, 136.0, 141.1, 166.2; MS
(EI, m/ z) 290 (29, M+), 248 (58, M+ - C3H6), 76 (100, M+ - C4H7-
IO2); HRMS calcd for C10H11IO2 289.9800, found 289.9786. Anal.
Calcd for C10H11IO2: C, 41.40; H, 3.82. Found: C, 41.28, H, 3.72.
N,N-Diisop r op yl-2-br om oben za m id e (1g): mp 147-149 °C
N,N,N′,N′-Tet r a isop r op yl-2,2′-b ip h en yld ica r b oxa m id e
(4g): mp 167-168 °C; IR (KBr) 1614, 1429, 1342, 1330 cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.79 (d, 6H, J ) 6.5 Hz), 1.07 (d,
6H, 6.6 Hz), 1.33 (d, 6H, 6.8 Hz), 1.49 (d, 6H, 6.8 Hz), 3.37 (sept,
2H, J ) 6.8 Hz), 3.96 (sept, 2H, 6.5 Hz), 7.28 (m, 6H), 7.50 (m,
2H); 13C NMR (50 MHz, CDCl3) δ 19.7, 20.2, 20.6, 21.0, 45.6,
50.4, 126.4, 127.3, 127.7, 130.3, 136.3, 138.4, 169.8; MS (EI, m/ z)
308 (100, M+ - C6H14N), 408 (19, M+); HRMS calcd for
C26H36N2O2, 408.2777, found 408.2777. Anal. Calcd for
(lit.4 141-145 °C); IR (CCl4) 1628, 1440, 1341 cm-1 1H NMR
;
(200 MHz, CDCl3) δ 1.06 (d, J ) 6.7 Hz, 3H), 1.23 (d, J ) 6.7
Hz, 3H), 1.56 (d, J ) 6.8 Hz, 3H), 1.58 (d, J ) 6.8 Hz, 3H), 3.56
(sept, J ) 6.8 Hz, 2H), 7.35 (m, 3H), 7.55 (d, J ) 7.9 Hz, 1H);
13C NMR (50 MHz, CDCl3) ppm 20.1 (q), 20.5 (q), 20.6 (q), 20.7
(q), 46.0 (d), 51.1 (d), 119.0 (s), 126.6 (d), 127.5 (d), 129.4 (d),
140.2 (s), 168.1 (s); MS (EI, m/ z) 283/285 (15, M+), 282/284 (15,
C
26H36N2O2: C, 76.43; H, 8.88; N, 6.86. Found: C, 76.26; H,
9.17; N, 6.86.
4-Br om o-1-h yd r oxy-8-m eth oxyn a p h th a len e (9). 1-Hy-
droxy-2-methoxynaphthalene (1.03 g, 5.9 mmol) was dissolved
in CCl4 (50mL). To the solution was added sodium hydride (142
mg, 5.9 mmol) followed by bromine (304 µL, 5.9 mmol). After
15 min at rt, the solution was diluted with ether and washed
with water followed by saturated Na2S2O3 solution. The ether
layer was dried (Na2SO4) and filtered, and the solvent was
M+ - H), 240/242 (43, M+ - C3H7), 183/185 (100, M+
-
N(C3H7)2). Anal. Calcd for C13H18BrNO: C, 54.94; H, 6.38; N,
4.93. Found: C, 55.02; H, 6.45; N, 4.91.
1-[(ter t-Bu tyldiph en ylsilyl)oxy]-4-br om oben zen e (1j). To
a solution of 4-bromophenol (3.96 g, 22.9 mmol) in DMF (50 mL)
were added tert-butyldiphenylsilyl chloride (4.82 mL, 27.5 mmol)
and imidazole (3.90 g, 57.2 mmol). The resulting solution was
stirred for 2 d at rt, quenched with H2O (50 mL), and stirred for
a further 30 min. The mixture was then diluted with ether (150
mL) and washed with 10% HCl and brine solution. The organic
phase was dried over anhydrous sodium sulfate, filtered, and
concentrated in vacuo to afford a light yellow oil. The crude
silane was distilled under reduced pressure to afford a clear,
colorless oil which later solidified (9.10 g, 96.7%): mp 43.5-45
°C; bp 130-150 °C (0.1 mmHg); IR (NaCl) 1486, 1272, 1251,
evaporated to afford
a blue oil. The crude material was
recrystallized from CH2Cl2/hexanes to give 0.98 g (67%) light
blue crystals which were determined by 1H NMR spectroscopy
to be a 9:1 mixture of 9 and 2-bromo-1-hydroxy-8-methoxynaph-
thalene. This mixture was used without further purification in
the subsequent benzylation step. An analytical sample of 9 was
obtained by radial chromatrography [elution with hexanes/ethyl
acetate (9:1)]: mp 111.5-113.5 °C; IR (KBr) 1392, 1260, 1080
1
cm-1; H NMR (200 MHz, CDCl3) δ 4.08 (s, 3H), 6.77 (d, 1H, J
) 8.3 Hz), 6.86 (d, 1H, J ) 7.8 Hz), 7.44 (t, 1H, J ) 8.5 Hz),
7.65 (d, 1H, J ) 8.3 Hz), 7.84 (d, 1H, J ) 8.7 Hz), 9.48 (s, 1H);
13C NMR (50 MHz, CDCl3) δ 56.4, 104.9, 111.1, 111.3, 116.2,
121.3, 127.0, 131.7, 134.3, 154.6, 156.2; MS (EI, m/ z) 102 (100),
173 (11, M+ - Br), 209/211 (58), 237/239 (25, M+ - CH3), 252/
254 (35, M+); HRMS calcd for C11H9BrO2 251.9786/253.9767,
found 251.9763/253.9755.
1
1113 cm-1; H NMR (200 MHz, CDCl3) δ 1.12 (s, 9 H), 6.66 (d,
2H, J ) 8.8 Hz), 7.20 (d, 2H, J ) 8.7 Hz), 7.41 (m, 6 H), 7.72
(dd, 4H, J ) 7.4 and 1.6 Hz); 13C NMR (50 MHz, CDCl3) δ 19.4,
26.5, 113.4, 121.5, 127.9, 130.1, 132.1, 132.5, 135.5, 154.8; MS
(EI, m/ z) 105 (56), 152 (54), 181 (31), 197 (39), 273 (52), 353/
355 (100, M+ - C4H9), 410/412 (4, M+); Anal. Calcd for C22H23
BrOSi: C, 64.23; H, 5.64. Found: C, 64.23; H, 5.55.
-
1-(Ben zyloxy)-4-br om o-8-m eth oxyn a p h th a len e (10). To
a solution of the starting naphthol (1.02 g, 4.04 mmol) in DMF
(25 mL) was added NaH (107 mg, 4.44 mmol) followed by benzyl
bromide (528 µL, 4.44 mmol). The resulting solution was stirred
at rt for a 36 h period, quenched with H2O, and diluted with
ether (100 mL). The organic layer was washed with 10% NaOH
and saturated brine solution. After the mixture was dried over
Na2SO4, the solvent was removed in vacuo to afford a yellow
solid. The two isomeric products were seperated by fractional
recrystalization from CH2Cl2/hexanes to afford the title com-
pound in quantitative yield (1.25 g): mp 95-96 °C; IR (KBr)
1582, 1568, 1364, 1268, 1051 cm-1; 1H NMR (200 MHz, CDCl3)
δ 3.97 (s, 3H), 5.20 (s, 2H), 6.80 (d, 1H, J ) 8.4 Hz), 6.96 (d, 1H,
J ) 7.8 Hz), 7.28-7.75 (m, 7H), 7.86 (dd, 1H, J ) 8.5 Hz and
1.0 Hz); 13C NMR (50 MHz, CDCl3) δ 56.4, 71.7, 107.2, 109.0,
114.3, 119.4, 120.1, 127.0, 127.7, 127.8, 128.4, 130.3, 135.0, 137.3,
156.2, 157.5; MS (EI, m/ z) 91 (100), 114 (26), 193/195 (25), 263
(3, M+ - Br), 342/344 (15, M+); HRMS calcd for C18H15BrO2
342.0256/344.0236, found 342.0238/344.0217. Anal. Calcd for
C18H15BrO2: C, 62.99; H, 4.40. Found: C, 62.89; H, 4.40.
1-Iod o-2-m eth oxyn a p h th a len e (2b). To a solution of 1-bro-
mo-2-methoxynaphthalene (3.03 g, 12.8 mmol) in THF (150 mL)
was added n-BuLi (2.5 M solution in hexanes, 5.6 mL, 14.1
mmol, 1.1 equiv) at -78 °C. To the cooled solution was then
added I2 (0.3 M solution in THF, 50 mL, 15.3 mmol, 1.3 equiv).
The vessel was then warmed to rt and stirred 1 h under an N2
atmosphere. The reaction contents were then diluted with water
(150 mL) and ether (250 mL). The organic phase was washed
with a saturated solution of Na2S2O3, dried over anhydrous
MgSO4, filtered, and concentrated in vacuo to afford a red oil
which later solidified. The crude material was recrystallized
from hexanes to afford the title compound (3.63 g) in quantitative
yield: mp 86-87 °C (lit.21 mp 88.5-89 °C); 1H NMR (200 MHz,
(13) Ullmann, F.; Loewenthal, O. J ustus Liebigs Ann. Chem. 1904,
332, 38.
(14) Pettit, M. R.; Tatlow, J . C. J . Chem. Soc. 1954, 1071.
(15) Weitzberg, M.; Abu-Shakra, E.; Azeb, A.; Aizenshtat, Z.; Blum,
J . J . Org. Chem. 1987, 52 (4), 529.
(16) Evers, R. C.; Moore, G. J . J . Polym. Sci., Part A: Polym. Chem.
1986, 24 (8), 1863.
(17) Hay, A. S. J . Org. Chem. 1969, 34, 1160.
(18) Cooke, A. S.; Harris, M. M. J . Chem. Soc. 1963, 2365.
(19) Gottarelli, G.; Spada, G. P. J . Org. Chem. 1991, 56, 2096.
(20) Larock, R. C.; Bernhardt, J . C. J . Org. Chem. 1977, 42, 1680.
(21) Wirth, H. O.; Ko¨nigstein, O.; Kern, W. J ustus Liebigs Ann.
Chem. 1960, 634, 84.
4,4′-(Dib en zyloxy)-5,5′-d im et h oxy-1,1′-b in a p h t h yl (11):
mp 243-245 °C; IR (KBr) 1586, 1277, 1103, 1054, 1033 cm-1
;
1H NMR (200 MHz, CDCl3) δ 4.00 (s, 6H), 5.30 (s, 4H), 6.9 (m,
4H), 7.05 (d, 2H, J ) 8.0 Hz), 7.14-7.50 (m, 10H), 7.68 (d, 4H,
J ) 6.8 Hz); 13C NMR (100 MHz, CDCl3) δ 56.4, 71.6, 106.3,
108.2, 118.1, 119.7, 126.3, 127.1, 127.5, 128.4, 132.0, 136.9, 137.8,

Notes
J . Org. Chem., Vol. 61, No. 26, 1996 9559
155.8, 157.4; MS (EI, m/ z) 91 (100), 345 (20), 435 (36, M+
-
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada (NSERC),
The Canadian Foundation for AIDS Research (CAN-
FAR), The Alberta Heritage Foundation for Medical
Research (AHFMR), The Izaak Walton Killam Founda-
tion, and The University of Calgary for financial sup-
port.
C7H7), 526 (28, M+); HRMS calcd for C36H30O4 526.2144, found
526.2124.
4,4′-Dih yd r oxy-5,5′-d im eth oxy-1,1′-bin a p h th yl (12). To
a solution of coupled product 11 (68.5 mg, 0.130 mmol) in CH2-
Cl2 (3 mL) and EtOH (1 mL) was added 10% wt/wt Pd/C (100
mg). The reaction vessel was purged with H2 and subsequently
stirred for 12 h under a hydrogen atmosphere. The reaction
contents were then filtered, and the filterings were washed with
CH2Cl2 (25 mL). The filtrate was concentrated in vacuo to afford
a clean white solid in quantitative yield: mp 269-271 °C; 1H
NMR (200 MHz, CDCl3) δ 4.11 (s, 6H), 6.79 (dd, 2H, J ) 7.6
and 0.8 Hz), 7.05 (m, 6H), 7.33 (d, 2H, J ) 7.8 Hz), 9.54 (s, 2H)
(lit.8 1H NMR (CDCl3) δ 4.10 (s, 6H), 9.53 (s, 2H)); 13C NMR (50
MHz, CDCl3) δ 56.3, 104.0, 110.1, 115.1, 120.8, 125.5, 129.6,
130.2, 136.1, 154.2, 156.4; MS (EI, m/ z) 300 (14, M+ - C2H6O)
316 (10, M+ - C2H6), 331 (6, M+ - CH3), 346 (100, M+); HRMS
calcd for C22H18O4 346.1205, found 346.1188.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra are availiable for compunds 9, 11, and 12 (6
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O9617880