Catalytic Intermolecular Ortho-Arylation of Phenols

Article abstract of DOI:10.1021/jo030157k

The use of rhodium catalysts such as [RhCl(PPh₃)₃] or [{RhCl(COD)}₂] with PiPr₂(OAr) or P(NMe ₂)₃ co-catalysts allows the ortho-selective intermolecular arylation of phenols. The reaction p

Full text of DOI:10.1021/jo030157k

Ca ta lytic In ter m olecu la r Or th o-Ar yla tion of P h en ols
Robin B. Bedford* and Michael E. Limmert
School of Chemistry, University of Exeter, Exeter EX4 4QD, U.K.
r.bedford@ex.ac.uk
Received May 7, 2003
The use of rhodium catalysts such as [RhCl(PPh3)3] or [{RhCl(COD)}2] with PiPr2(OAr) or P(NMe2)3
co-catalysts allows the ortho-selective intermolecular arylation of phenols. The reaction proceeds
via orthometalation of P-OAr groups and then transesterification liberates the product phenol.
When 2-substituted phenols are used as substrates, [RhCl(PPh3)3]/iPr2(OAr) mixtures are typically
the catalysts of choice, whereas for substrates without 2-substitution [{RhCl(COD)}2]/P(NMe2)3
mixtures tend to give better results.
SCHEME 1. Ca ta lytic Or th o-Ar yla tion of P h en ols
In tr od u ction
The biaryl subunit is an important structural motif
that is found in a wide range of compounds such as
natural products, polymers, liquid crystals, and ligands
for homogeneous transition metal catalysts.1 One class
of reaction that provides particular challenges for the
catalytic chemist is the synthesis of ortho-arylated phe-
nols. Currently the most commonly used catalytic routes
to these compounds employ Suzuki or Stille coupling
reactions.2 These require the introduction and subse-
quent loss of stoichiometric amounts of either boronic
acid/ester or organotin functions. In addition it may prove
necessary to protect the phenolic hydroxide function
during the course of the coupling reactions, and this in
turn adds further steps to the synthetic procedure.
Regardless, such catalytic routes are often preferential
to stoichiometric processes, which tend to require equimo-
lar or greater amounts of reagents such as arylleads3 or
arylbismuths.4 Therefore the ability to couple an aryl
halide directly with a phenol (Scheme 1) without the need
for either (a) a sacrificial electrophilic boron or tin
fragment or (b) the introduction and subsequent removal
of a protecting group would be highly desirable from both
synthetic and atom-economic points of view.
SCHEME 2
SCHEME 3
SCHEME 4
The transition-metal-catalyzed ortho-selective aryla-
tion of phenols has been limited to a few examples of
intramolecular couplings of aryl halides that are tethered
to the phenolic substrates (Scheme 2)5 and the reactions
of aryl halides with 2-aryl-substituted phenols (Scheme
3) or with 1-naphthol (Scheme 4).6
In all of these cases the reactions proceed via the
formation of stable five- or six-membered metallacycles.
Simple phenols avoid orthometalation reactions with late
transition metals, as this would give unfavorably strained,
four-membered metallacycles,7 and therefore these reac-
(1) (a) Stanforth, S. P. Tetrahedron 1998, 54, 263-303. (b) Bring-
mann, G.; Walter, R.; Weirich, R. Angew Chem., Int. Ed. Engl. 1990,
29, 977.
(2) For recent examples, see: (a) Zhuravel, M. A.; Nguyen, S. T.
Tetrahedron Lett. 2001, 42, 7925. (b) Kranich, R.; Eis, K.; Geis, O.;
Mu¨hle, S.; Bats, J . W.; Schmalz, H.-G. Chem. Eur. J . 2000, 6, 2874.
(c) Simonsen, K. B.; Gothelf, K. V.; J øergensen, K. A. J . Org. Chem.
1998, 63, 7536. (d) Zembower, D. E.; Zhang, H. J . Org. Chem. 1998,
63, 9300. (e) Yonezawa, S.; Komurasaki, T.; Kawada, K.; Tsuri, T.; Fuji,
M.; Kugimiya, A.; Haga, N.; Mitsumori, S.; Inagaki, M.; Nakatani, T.;
Tamura, Y.; Takechi, S.; Taishi, T.; Ohtani, M. J . Org. Chem. 1998,
63, 5831.
(5) (a) Hennings, D. D.; Iwasa, S.; Rawal, V. H. J . Org. Chem. 1997,
62, 2. (b). Hennings, D. D.; Iwasa, S.; Rawal, V. H. Tetrahedron Lett.
1997, 38, 6379.
(6) (a) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1740. (b) Satoh, T.; Inoh, J .; Kawamura,
Y.; Kawamura, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc. J pn. 1998,
71, 2239.
(3) Saito, S.; Kano, T.; Muto, H.; Nakadai M.; Yamamoto, H. J . Am.
Chem. Soc. 1999, 121, 8943 and references therein.
(4) Fedorov, A. Combes S. Finet, J .-P. Tetrahedron 1999, 55, 1341.
10.1021/jo030157k CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/01/2003
J . Org. Chem. 2003, 68, 8669-8682
8669

Bedford and Limmert
SCHEME 5
SCHEME 6
tions cannot be readily extended to such substrates.
However when aryloxide groups are incorporated into
phosphorus donors such as phosphites, P(OAr)3, or phos-
phinites, PR2(OAr), then facile orthometalation can occur
to give low-strain, five-membered metallacyles (Scheme
5).
Lewis exploited this phenomenon when he demon-
strated that ruthenium triarylphophite complexes cata-
lyze the ortho-specific deuteration and ethylation of
phenol.8,9 These catalytic processes rely on the reversible
in situ “transesterification” of catalytic amounts of triaryl
phosphite ligands with the substrate phenols. These
findings led to the development of a range of new
catalytic reactions that proceed via an orthometalation
and subsequent insertion of an unsaturated substrate
into the new M-C bond.10 By contrast, intermolecular
ortho-selective couplings that proceed via the coupling
of an orthometalated carbon with a substrate introduced
by oxidative addition of an organic halide remain very
rare. Recently Yamaguchi and co-workers demonstrated
that phenols can be coupled with haloalkynes in the
presence of a gallium catalyst, and Oi and co-workers
showed that arylimines can be coupled with aryl bro-
mides in the presence of a ruthenium catalyst.11,12 We
were interested to see whether catalytic transesterifica-
tion of phenols and their subsequent C-H activation by
orthometalation could be used to realize the intermo-
lecular ortho-arylation of these substrates (Scheme 1).
It can be envisaged that such a process may proceed via
a mechanism related to that shown in Scheme 6, in which
two interlinked catalytic pathways lead to the ortho-
arylation of the phenol incorporated in a PR2(OAr) ligand,
followed by a transesterification of the modified PR2(OAr)
ligand to liberate the product phenol. If this could be
realized, it should allow the synthesis of a wide range of
selectively 2-arylated phenols. The results of our study
into the inception and development of this new catalytic
process are presented below.13
hindered functions in the 2-position, as we anticipated
this would give us the greatest chance of success since
orthometalation is accelerated by steric bulk. In addition,
by blocking off one of the ortho-positions, the number of
potential side products that could be formed is reduced.
The substrates used in the optimization studies are the
bulky phenol 2,4-di-tert-butylphenol, since phosphorus
donors that incorporate this aryloxide residue have been
found to undergo particularly facile orthometalation
reactions,14 and 4-bromoacetophenone, which is electroni-
cally activated with respect to oxidative addition.
Initial experiments focused on the use of either (i)
palladium catalysts formed in situ from dipalladium tris-
(dibenzylideneacetone) with the ligands tris(2,4-di-tert-
butylphenyl)phosphite (1), (2,4-di-tert-butylphenyl) diphe-
nylphosphinite (2), or (2,4-di-tert-butylphenyl) diisopropyl-
phosphinite (3a ) acting as co-catalysts or (ii) preformed
palladacyclic catalysts of the type 4 containing these and
related ligands.14b,c,e,15 In all cases we observed either no
reaction or the oxidative coupling of the phenol to give
2,2′,4,4′-tetra-tert-butylbiphenol, 5.
Resu lts a n d Discu ssion
Scr een in g of Ca ta lysts a n d Op tim iza tion u sin g
2-Su bstitu ted P h en ols. In the first instance, to probe
the feasibility of the reaction, we limited our investigation
to the potential ortho-arylation of phenols with sterically
(7) Miura and co-workers have demonstrated the 1-arylation of
2-naphthols. This pattern of reactivity may result from the high
susceptibility of the 1-position to electrophilic attack rather than the
formation of a highly strained four-membered palladacycle. See ref 6.
(8) Lewis, L. N. Inorg. Chem. 1985, 24, 4433.
(9) Lewis L. N.; Smith, J . F. J . Am. Chem. Soc. 1986, 108, 2728.
(10) For recent reviews, see: (a) Ritleng, V.; Sirlin, C.; Pfeffer, M.
Chem. Rev. 2002, 102, 1731. (b) Dyker, G. Angew. Chem., Int. Ed. 1999,
38, 1699.
(11) Kobayashi, K.; Arisawa, M.; Yamaguchi, M. J . Am. Chem. Soc.
2002, 124, 8528.
(12) Oi, S.; Ogino, Y.; Fukita, S.; Inoue, Y. Org. Lett. 2002, 4, 1783.
(13) Aspects of this work have been communicated previously:
Bedford, R. B.; Coles, S. J .; Hursthouse, M. B.; Limmert, M. E. Angew.
Chem., Int. Ed. 2003, 42, 112.
By contrast, when [RhCl(PPh3)3], Wilkinson’s catalyst,
is employed with an appropriate co-catalyst, then the
reaction proceeds as shown in Scheme 1 to give the ortho-
arylated phenol 2,4-di-tert-butyl-6-(4′-acetylphenyl)phe-
nol, 6a . The choice of co-catalyst is important. The
reaction works with the bulky triaryl phosphite ligand 1
only if it is used in 100 mol % loading (i.e., no free phenol
8670 J . Org. Chem., Vol. 68, No. 22, 2003

Catalytic Ortho-Arylation of Phenols
is used in the reaction). This implies that transesterifi-
cation works, at best, only very poorly with this ligand.
In addition it is necessary to use 30 mol % of Wilkinson’
catalysts and a large excess (3.5 equiv) of aryl bromide
is required, otherwise the major product formed is again
the homocoupled biphenol, 5. The triarylphosphinite
ligand 2 suffers from most of these limitations as well,
although the reaction proceeds when only 1.5 equiv of
the aryl bromide are used. However, when it is replaced
by the aryl dialkylphosphinite 3a , then the reaction is
far more efficient and transesterification becomes viable;
thus high yields of the product 6a are obtained with 5
mol % Rh, 15 mol % 3a , and 1.5 equiv of 4-bromoaceto-
phenone (Table 1, entry 1). Although the reaction pro-
ceeds well in toluene, the use of 1,4-dioxane leads to
complete inactivity. Lowering the catalyst and co-catalyst
loadings to 3 mol % rhodium and 10 mol % 3a leads to a
similar yield of product (88%). The catalyst and co-
catalyst loadings can be dropped further (vide infra), but
for the remainder of the initial coupling reactions the
non-optimized levels of 5 mol % Rh and 15 mol %
phosphinite co-catalyst were used.
the fact that while the C-Cl bond of 4-chlorobromoben-
zene is deactivated with respect to oxidative addition,
arylation of the para-position activates it. This implies
that when aryl chlorides are used the rate-determining
step is probably oxidative addition.
To establish whether oxidative addition of aryl bromide
substrates is also rate-determining, we performed a
competitive coupling of 2-tert-butylphenol with 1 equiv
each of the electronically deactivated (with respect to
oxidative addition) aryl bromide 4-bromo-N,N-dimethyl-
amine and the nonactivated substrate 4-bromotoluene (eq
1). In this case we found that quantitative conversion of
the phenol to coupled products occurs with the two
possible products 6w and 6f formed in identical amounts.
This implies that with aryl bromides, unlike with aryl
chlorides, oxidative addition is not the rate-determining
step.
The “standard” loading of aryl bromides was main-
tained at 1.5 equiv compared with the total phenol
content (including that incorporated in the phosphinite
co-ligands), because in certain (but no means all) cases
hydrodehalogenation of the aryl bromide occurs, thus
lowering the amount available for reaction. In principle
any OAr function can be incorporated into the phosphin-
ite co-catalyst, but for ease of product identification and
purification we typically employed phosphinites that
contain the substrate phenol. The data from the catalytic
studies with Wilkinson’s catalyst and the aryl dialkyl-
phosphinite ligands acting as co-catalysts are sum-
marized in Table 1. The yields quoted are isolated yields
based on the amount of free phenol used, since in many
cases the hydrolytic workup did not lead to complete or
substantial hydrolysis of the phosphinites.
In all cases where the phenol substrate is unsubsti-
tuted at the 4-position only ortho-arylation occurs; a
simple electrophilic reaction of these substrates should
also lead to the formation of para-arylated products. This
demonstrates that the reaction is indeed ortho-selective,
which in turn implies that the C-H activation of the
phenol occurs after it has been incorporated into the
phosphinite co-catalyst.
As can be seen from entries 1-8, good to excellent
conversions to the ortho-arylated phenols are seen re-
gardless of whether the aryl bromide used is activated,
nonactivated, or deactivated with respect to oxidative
addition. The reaction also proceeds smoothly when
sterically hindered aryl bromide substrates are employed
(entries 9-12). Even aryl chlorides can be used as
substrates (entries 13 and 14), although much lower
yields of coupled products result. The lower activity in
the coupling of aryl chlorides compared with aryl bro-
mides is further illustrated by the reaction of 4-chloro-
bromobenzene with 2-tert-butylphenol (entry 14). Here
two products are formed: the 1,4-dicoupled product, 9,
and 2-tert-butyl-6-(4′-chlorophenyl)phenol, 6n . No 2-tert-
butyl-6-(4′-bromophenyl)phenol is observed in the product
mix. This product distribution presumably results from
In certain cases the reaction does not stop at the simple
ortho-arylated products and arylation of a previously
introduced ortho-aryl group occurs (entries 5, 6, 8, 16-
18, 21). Such multiple arylation reactions have been
observed before and proceed by essentially the same route
as shown in Scheme 3 for the arylation of 2-phenylphe-
nol.6
As well as simple aryl halides, heteroaryl bromides can
be used as coupling partners (entries 15-18). The
particularly low yield obtained with 2-bromopyridine
maybe be due, in part, to deactivation of the catalyst since
both the product phenol and, in particular, the interme-
diate modified phosphinite can form chelate complexes
with the metal center. Both 3-bromo- and 3-bromo-4-
methylthiophene couple with 2-tert-butylphenol but are
then subject to further arylations. 2-Bromothiophene
gives only trace amounts of mono- and diarylated prod-
ucts as determined by GC-MS. The poor results here
are again presumably due to catalyst inhibition by
chelate formation.
(14) (a) Bedford, R. B.; Castillon, S.; Chaloner, P. A.; Claver, C.;
Fernandez, E.; Hitchcock, P. B.; Ruiz, A. Organometallics 1996, 15,
3990. (b) Albisson, D. A.; Bedford, R. B.; Lawrence, S. E.; Scully, P. N.
Chem. Commun. 1998, 2095. (c) Bedford, R. B.; Welch, S. L. Chem.
Commun. 2001, 129. (d) Bedford, R. B.; Hazelwood, S. L. Organome-
tallics 2002, 21, 2599. (e) Bedford, R. B.; Hazelwood, S. L.; Limmert,
M. E.; Brown, J . M.; Ramdeehul, S.; Cowley, A. R.; Coles S. J .;
Hursthouse, M. B. Organometallics 2003, 22, 1364. (f) Bedford, R. B.;
Hazelwood, S. L.; Limmert, M. E.; Albisson, D. A.; Draper, S. M.; Scully,
P. N.; Coles S. J .; Hursthouse, M. B. Chem. Eur. J . 2003, 9, 3216.
(15) Bedford, R. B.; Hazelwood, S. L.; Limmert, M. E. Chem.
Commun. 2002, 2610.
It is not necessary to have a bulky tert-butyl in the
2-position of the phenol for the reaction to proceed; the
incorporation of progressively smaller groups such as
isopropyl and ethyl still gives reasonable yields of the
products (entries 19 and 20). Coupling is even seen with
2-methylphenol (entry 21); however, in this case the yield
J . Org. Chem, Vol. 68, No. 22, 2003 8671

Bedford and Limmert
TABLE 1. Ca ta lytic Or th o-Ar yla tion of P h en ols w ith 2-Su bstitu en tsa
8672 J . Org. Chem., Vol. 68, No. 22, 2003

Catalytic Ortho-Arylation of Phenols
TABLE 1 (Con tin u ed )
a
Conditions: 2-substituted phenol (or naphthol) (1.0 mmol), aryl halide (1.5 mmol), Cs2CO3 (1.7 mmol), [RhCl(PPh3)3] (5 mol %),
PR2(OAr), (15 mol %), toluene, reflux, 18 h. Isolated yields after chromatography, not optimized. c Estimated by 1H NMR spectroscopy.
Isolated yield of microanlaytically pure 6v, 39%.
b
d
is significantly lower. It is not necessary to have an alkyl
group in the 2-position to facilitate the coupling reaction;
1-naphthol can also be used as a substrate to good effect
(entry 22). In this case a small amount of the 2,8-
diarylated product, 10v, is observed. Presumably the
8-arylation occurs after the 2-arylation as there is no
evidence for the formation of the 8-monoarylated naph-
thol. It is possible that the 8-arylation does not proceed
via the orthometalation of a phosphinite intermediate,
since 1-naphthol itself has been shown to undergo 8-ary-
lation in the presence of a palladium catalyst as shown
in Scheme 4.6
No activity is observed with unsubstituted phenol. The
observed reduction in catalytic activity with decreasing
steric bulk implies that, with aryl bromide substrates,
the rate-determining step is probably the orthometalation
of the phosphinite ligand.
the amount of rhodium needed, (ii) reduce the loading of
co-catalyst, (iii) employ a cheaper base, (iv) establish the
role of the phosphine co-ligands, and (v) extend the
reaction to phenols without 2-substitution. The latter
point will be discussed later. To address points i-iv we
chose the coupling of 2-isopropylphenol with 4-bromoani-
sole as a standard reaction, as it proceeds reasonably well
(Table 1, entry 19) but has scope for improvement,
making it ideal for optimization studies. The results from
this study are summarized in Table 2.
In all cases [{Rh(µ-Cl)(COD)}2] was used as the rhod-
ium source. As can be seen in entry 1, the use of a catalyst
formed in situ from this dimer and 2 equiv per Rh of PPh3
gives a performance very similar to that of the catalyst
formed from Wilkinson’s catalyst and the phosphinite co-
catalyst (Table 1, entry 19). Reducing the number of
equivalents of co-ligand from 2 to 1 per rhodium does not
perturb the system too greatly (Table 2, entry 2), nor does
halving the rhodium loading while increasing the co-
catalyst:Rh ratio to 3:1 (entry 3). However, when the
Having established a protocol for the ortho-arylation
of phenols with 2-substitution, we wished to see whether
it was possible to refine the process to be able to (i) reduce
J . Org. Chem, Vol. 68, No. 22, 2003 8673

Bedford and Limmert
TABLE 2. Effect of Va r yin g Con d ition s a n d Liga n d s on
th e Or th o-Ar yla tion Rea ction a
substantial decrease in activity. This may imply that the
mechanism for orthometalation is in fact electrophilic
displacement. However, if this was the case, it would be
anticipated that the use of co-catalysts that are poorer
σ-donors and better π-acids than PiPr2(OAr) would give
better results, but as discussed in the initial optimization
studies, PPh2(OAr) and P(OAr)3 ligands make progres-
sively poorer co-catalysts while their net donation of
electron-density to the rhodium center decreases. Alter-
native explanations are that the catalysts formed in situ
with PCy3 or PtBu3 are too crowded to facilitate ortho-
metalation or that the rhodium center is now too electron-
rich and the rate-determining step is shifted to reductive
elimination.
Scr een in g of Ca ta lysts a n d Op tim iza tion for P h e-
n ols w ith ou t 2-Su bstitu tion . Obviously it would be
highly desirable if the catalytic methodology could be
modified to allow facile and clean ortho-arylation of
phenols without 2-substitution. It appears as if the rate-
determining step with small phenols is orthometalation,
and therefore we wondered whether the use of iridium-
based catalysts may prove advantageous since bulky
phosphite ligands undergo particularly facile orthometa-
lation reactions with this metal.14a Unfortunately when
either a mixture of [{IrCl(COD)}2]/2 PPh3/PiPr2(OAr) or
[{IrCl(COE)2}2]/2 PPh3/PiPr2(OAr) were used as precata-
lysts in the coupling of the small substrate 2-methylphe-
nol with 4-bromoanisole, no reaction was observed.
Therefore we concentrated instead on rhodium-based
systems with a range of co-catalysts with variable steric
and electronic properties. For the optimization we focused
on the coupling of phenol with 4-bromoanisole in toluene
with cesium carbonate as base, and the results of this
study are summarized in Figure 1.
phosphinite
loading
added
ligand L
(equiv
(equiv
conv
(%)b
entry mol % Rh
per Rh)
per Rh)
base
1
2
3
4
5
6
7
8
9
10
11
12
13
5.0
5.0
2.5
1.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2
1
3
3
3
3
3
3
3
3
3
3
3
PPh3 (2)
PPh3 (2)
PPh3 (2)
PPh3 (2)
PPh3 (2)
PPh3 (2)
PPh3 (4)
PPh3 (3)
PPh3 (2)
PPh3 (1)
0
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
68
62
62
43
22
88
76
78
74
72
74
45
34
K3PO4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
PCy3 (3)
PtBu3 (3) Cs2CO3
a
Conditions: 2-isopropylphenol (1.0 mmol), 4-bromoanisole (1.5
mmol), base (1.7 mmol) [{RhCl(COD)}2] (1-5 mol %), 3d (1-3
b
equiv per Rh), toluene (10 mL), reflux temperature, 18 h. Con-
version determined by 1H NMR using 1,3,5-trimethoxybenzene in
CDCl3 as an internal standard.
rhodium loading is reduced further to 1 mol %, some loss
in performance is observed.
We were keen to find if it is possible to replace the
rather expensive base, cesium carbonate, with a cheaper
alternative. While potassium carbonate does not seem
to be particularly useful, changing to potassium phos-
phate actually appears to be beneficial to catalyst per-
formance, with a substantial increase in conversion
observed (entry 6).
In an attempt to accelerate the orthometalation process
we initially investigated the application of the bulkier
phosphinite co-catalyst PtBu2(OPh), 3e, formed by reac-
tion of PtBu2Cl with sodium phenoxide. We were pleased
to see that at 15 mol % loading of 3e, some conversion to
the diarylated product, 11a , and the triarylated product,
12, occurred, and even greater conversion was obtained
with 30 mol % loading of the co-catalyst (Figure 1,
catalysts a and b respectively). When the aryl bromide
is changed to 2-bromo-p-xylene, the diarylated product
2,5,2′′,5′′-tetramethyl-[1,1′;3′,1′′]terphenyl-2′-ol, 11b , is
obtained in 34% yield (eq 2).
To address the role played by the supporting ligands
in the catalysis we studied the effect of changing the
relative amounts and type of added phosphines. We were
very surprised to find that when the ratio of PPh3:Rh is
varied from 4:1 to 0:1 there is essentially no difference
in conversion (compare entries 7-11). This implies that
the triphenylphosphine does not play any particular role
and can be omitted from the reaction. Thus when
Wilkinson’s catalyst is used, it is presumably only acting
as a soluble source of rhodium(I) for the reaction. It is
possible that if, as discussed earlier, the rate-determining
step is indeed orthometalation, there is insufficient
difference in the donor properties of the PPh3 co-ligand
and the PiPr2(OAr) co-catalyst to effect the rate regard-
less of the number of each type of ligand on the metal
center. To increase the rate of orthometalation, assuming
it occurs via oxidative addition of the C-H bond rather
than by electrophilic displacement,16 it would be neces-
sary to increase the electron density on the rhodium
center. The use of trialkylphosphine co-ligands would be
expected to do this. However, as can be seen in entries
12 and 13 the use of either PCy3 or PtBu3 leads to a
The product distribution in both of these reactions
implies that the rate-determining step with phenol is
(16) For a discussion on the mechanisms of cyclometalation, see:
Ryabov; A. D. Chem. Rev. 1990, 90, 403.
8674 J . Org. Chem., Vol. 68, No. 22, 2003

Catalytic Ortho-Arylation of Phenols
F IGURE 1. Coupling of phenol with 2-bromoanisole with varying catalysts/co-catalysts.
again probably orthometalation. The absence of monoary-
lated phenol means the rate of arylation of the 2-arylated
phenol must be much higher than that for the arylation
of phenol. This is presumably because the larger size of
the intermediate phosphinite leads to a greater rate of
orthometalation.
became aware that Oi and co-workers have indepen-
dently found this Rh-P(NMe2)3-based system to be active
for the ortho-arylation of phenols; these results were
presented at the 81st annual meeting of the J apanese
Chemical Society.17
These optimization results seem a little surprising in
the sense that, under the conditions we are employing,
it would be expected that all of the P(NMe2)3 would be
converted to P(OPh)3 and yet the results obtained with
these two ligands are quite different. One possible
explanation for this observation is that the transesteri-
fication does not happen on the free ligands but rather
is mediated by the rhodium. Given that the ratio of
P(NMe2)3 to rhodium is 3:1, it is highly likely that all of
the co-catalyst is coordinated to the rhodium and that
transesterification may indeed occur in the coordination
sphere.
Having established that mixtures of [{RhCl(COD)}2]
and P(NMe2)3 can be used to good effect for the coupling
of unsubstituted phenol, we then investigated the ap-
plication of this catalyst system to a range of coupling
reactions. The results of this study are summarized in
Table 3. In some cases the isolated yields are low; this is
due to the fact that isolation of the pure compounds by
While increasing the steric bulk of the alkyl substit-
uents on the phosphinite co-catalyst does indeed appear
to open up the possibility of using phenols without
2-substitution as substrates, the overall yield and selec-
tivity is too low to be of use. Therefore we next decided
to investigate the effect of changing the electronics of the
co-ligand. We were surprised to find that the small,
π-acidic ligand triphenyl phosphite could be used as a
co-catalyst (Figure 1, catalyst c). Although the conversion
to coupled products observed is poor, the selectivity for
diarylation rather than triarylation is high with only
trace amounts of 12 observed. When first one and then
two of the OPh residues are replaced by NMe2 in the co-
catalyst, the conversion increases. Since the co-catalysts
P(NMe2)(OPh)2 and P(NMe2)2(OPh) are readily prepared
by reaction of appropriate amounts of phenol with
P(NMe2)3 in toluene at reflux temperature, we wondered
whether P(NMe2)3 itself would act as a useful co-catalyst.
This indeed proves to be the case, with a respectable
conversion to the diarylated product 11a of 71% and good
selectivity observed. During the course of this work we
(17) Fukita, S.; Watanabe, S.; Oi, S.; Inoue, Y. Abstracts of the 81st
Annual Meeting of J apan Chemical Society, 2002; p 1108, 1G5-40.
J . Org. Chem, Vol. 68, No. 22, 2003 8675

Bedford and Limmert
TABLE 3. Ca ta lytic Or th o-Ar yla tion of P h en ols w ith ou t 2-Su bstitu en tsa
8676 J . Org. Chem., Vol. 68, No. 22, 2003

Catalytic Ortho-Arylation of Phenols
TABLE 3 (Con tin u ed )
a
Conditions: phenol (or naphthol) (1.0 mmol), aryl halide (1.5 mmol), Cs2CO3 (1.7 mmol), [{RhCl(COD)}2] (10 mol % Rh), P(NMe2)3,
(30 mol %), toluene, reflux, 18 h. Isolated yields of microanalytically pure product after chromatography, not optimized. c Determined
b
by 1H NMR spectroscopy. Isolated yield of microanlaytically pure 11a , 31%. e Isolated yield of microanalytically pure 6a d , 38%.
d
chromatography, particularly when large amounts of
secondary coupled products are present, proved problem-
atic. The yields refer only to the amount of product
isolated microanalytically pure, unless otherwise indi-
cated.
than when using the phosphinite-based protocol. There-
fore although the latter method is useful for phenols
without 2-substitution, the lower rhodium loading means
that the earlier method is more applicable for most
2-substituted phenols. Even more striking is the poor
yield obtained in the coupling of 2-tert-butylphenol with
4-bromoanisole (entry 13) compared with that obtained
using the earlier method (Table 1, entry 4). It seems that
in most cases where the phenol is 2-substituted the
method outlined in Table 1 gives superior yields. How-
ever, if a reaction with a 2-susbtituted phenol fails using
the phosphinite-based method, e.g., when using 2-phe-
nylphenol or 2-methoxyphenol as substrates or when
coupling 1-naphthol with 4-bromoanisole, it is worth
trying the second, complementary P(NMe2)3-based pro-
tocol.
As well as reacting with the electronically deactivated
substrate 4-bromoanisole (entry 1), phenol can be coupled
with the hindered aryl bromide bromomesitylene; how-
ever, the yield of the dicoupled product 11c obtained after
18 h is poor (entry 2). When 3-substituted phenols are
used as substrates, monosubstituted phenols 6 are also
produced in which the arylation occurs solely in the
6-position, presumably because of the steric bulk of the
3-subsituent. Thus both 3-methylphenol and 3-methoxy-
phenol react to give the 6-monoarylated species 6x and
6y, respectively, as well as the 2,6-diarylated species 11x
and 11y (entries 3 and 4). The absence of any 2-monoary-
lated products indicates that the 6-arylation occurs first.
It is particularly interesting to note that no 2-monoary-
lation occurs with 3-methoxyphenol, as this indicates that
the selectivity is purely steric in basis with no accelera-
tion of 2-arylation by precoordination of the methoxy
group to the rhodium center. When the size of the
3-substituent is increased, e.g., in the case of 3-tert-
butylphenol (entry 5), no 2-aryation is observed and the
6-monoarylated phenol, 6z, is obtained as the sole
product. 2-Naphthol can also be used as a substrate,
again giving a mixture of the mono- and diarylated
compounds 6a a and 11a a (entry 6).
Su m m a r y
In summary, we have developed the catalytic ortho-
arylation of phenols as a viable process. In many cases
high yields and high selectivity result. It appears that
the precise nature of the P-OAr-containing co-catalyst is
highly important, and as yet, one class of ligand does not
work in all cases. For most phenol substrates with
2-substituents the diisopropylphosphinite, PiPr2(OAr),
ligands are the best tested, whereas for substrates
without 2-substituents tris(dimethylamino)phosphine,
P(NMe2)3, is a much better choice. Obviously it is still
necessary to work on the systems in order to bring down
further the catalyst loading and, in certain cases, increase
the yield and/or the product selectivity of the reactions.
This work is currently ongoing in our group.
Neither 2-phenylphenol nor 2-methoxyphenol are ortho-
arylated effectively when using the protocol outlined in
Table 1. However, the use of P(NMe2)3 as a co-catalyst
allows both to be ortho-arylated in the 6-position to give
6a b and 6a c, respectively (entries 7 and 8). This meth-
odology can also be used to couple 1-naphthol with
4-bromoanisole (entry 9), a reaction that fails with the
earlier methodology.
Exp er im en ta l Section
Syn th esis of P h osp h in ite Liga n d s 3c a n d 3d . The
ligands 3c and 3d were prepared using an analogous method
to that described peviously for the synthesis of 3a and
b.18
Da ta for 3c. Colorless oil; 1H NMR (300 MHz, CDCl3) δ
1.19 (m, 12 H), 2.06 (apparent d of sept., J ) 7.2, 2.8 Hz, 2H),
7.36 (m, 2H), 7.47 (m, 3H), 7.80 (m, 1H), 8.25 (m, 1H); 31P NMR
(121 MHz, CDCl3) δ 147.
By comparing the formation of 6s under these condi-
tions (entry 10) with those used in Table 1 (entry 19), it
can be seen that there is not any significant increase in
conversion, despite the fact that the loading of rhodium
is double that used in the earlier method. The yields from
the reactions of 4-bromoanisole with 2-ethylphenol and
2-methylphenol are significantly and marginally better,
respectively, under the conditions used in Table 3 (entries
11 and 12) compared with the same couplings in Table 1
(entries 20 and 21), although in the latter case the second,
diarylated product 7u is formed in far greater amounts
Da ta for 3d . Colorless oil; 1H NMR (300 MHz, CDCl3) δ
1.22 (m, 12 H), 1.24 (d, J ) 6.9 Hz, 6H), 1.98 (apparent d of
sept., J ) 7.0, 2.0 Hz, 2H), 3.0 (sept., J ) 6.9 Hz, 1H), 6.93
(ddd, J ) 7.4, 7.3, 0.8 Hz, 1H), 7.03 (ddd, J ) 8.1, 7.3, 1.6 Hz,
1H), 7.11 (dd, J ) 7.4, 1.6 Hz, 1H), 7.25 (ddd, J ) 8.1, 0.8 Hz,
J (H, P) ) 4.7 Hz, 1H); 31P NMR (121 MHz, CDCl3) δ 143.
(18) Bedford, R. B.; Hazelwood, S. L.; Horton, P. N.; Hursthouse,
M. B. Dalton Trans. 2003, in press.
J . Org. Chem, Vol. 68, No. 22, 2003 8677

Bedford and Limmert
Gen er a l Ca ta lytic Meth od ology u sin g Wilk in son ’s
Ca ta lysts a n d Ar ylp h osp h in ite Co-ca ta lysts (Ta ble 1). In
a Radleys reaction tube under nitrogen were added [RhCl-
(PPh3)3] (46 mg, 0.05 mmol), toluene (10 mL), the appropriate
aryl halide (1.5 mmol), phosphinite (0.15 mmol), 2-substituted
phenol (or 1-naphthol) (1.0 mmol), and Cs2CO3 (0.550 g, 1.70
mmol). The mixture was heated at reflux temperature for 18
h and allowed to cool, and then HCl (aq) (2 M, 5 mL) was
added. The organic phase was extracted with dichloromethane
(3 × 25 mL), dried (MgSO4), and filtered, and the solvent
removed under reduced pressure. The crude mixture was then
subjected to column chromatography (silica).
3,5-Di-ter t-bu tyl-[1,1′;2′,1′′]ter p h en yl-2-ol (7e). Colorless
oil; Rf 0.50 (CHCl3/hexane, 1:3); 1H NMR (300 MHz, CDCl3) δ
1.18 (s, 9H), 1.29 (s, 9H), 4.92 (s, 1H), 6.84 (d, J ) 2.4 Hz,
1H), 7.09 (m, 2H), 7.16 (m, 4H), 7.50 (m, 4H); 13C NMR (75.5
MHz, CDCl3) δ 29.5, 31.5, 34.1, 34.8, 122.9, 126.0, 126.7, 127.2,
127.8, 128.1, 128.5, 129.1, 130.5, 131.2, 135.0, 136.0, 140.5,
141.8, 142.3, 148.6; HRMS (CI) calcd for C26H31O [M+ + H]
359.2375, found 359.2321.
2,4-Di-ter t-bu tyl-6-[1,1′;3′,1′′]ter ph en yl-2′-yl-ph en ol (8e).
Colorless oil; Rf 0.38 (CHCl3/hexane, 1:3); 1H NMR (300 MHz,
CDCl3) δ 0.99 (s, 9H), 1.12 (s, 9H), 4.64 (s, 1H), 6.55 (d, J )
2.3 Hz, 1H), 6.91 (d, J ) 2.3 Hz, 1H), 7.12 (m, 10H), 7.52 (m,
3H); 13C NMR (75.5 MHz, CDCl3) δ 29.3, 31.3, 33.8, 34.5, 121.9,
121.9, 125.6, 126.5, 127.3, 127.5, 128.4, 129.2, 129.7, 134.5,
141.0, 141.4, 143.3, 148.7; HRMS (CI) calcd for C32H35O [M+
+ H] 435.2688, found 435.2650.
Cou p lin g of 2,4-Di-ter t-bu tylp h en ol w ith 4-Br om oa ce-
top h en on e (Ta ble 1, en tr y 1). Phosphinite ligand 3a used.
3,5-Di-ter t-bu tyl-4′-a cetyl-bip h en yl-2-ol (6a ). Colorless
solid, 313 mg (96%); Rf 0.11 (CHCl3/hexane, 1:1); 1H NMR (300
MHz, CDCl3) δ 1.34 (s, 9H), 1.46 (s, 9H), 2.66 (s, 3H), 5.22 (s,
1H), 7.08 (d, J ) 2.5 Hz, 1H), 7.38 (d, J ) 2.5 Hz, 1H), 7.60 (d,
J ) 8.1 Hz, 2H), 8.08 (d, J ) 8.1 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 25.6, 28.7, 30.6, 33.3, 34.1, 123.5, 123.5, 126.0, 128.3,
128.8, 134.9, 135.2, 141.5, 142.2, 147.5, 196.5; HRMS (CI) calcd
for C22H29O2 [M+ + H] 325.2167, found 325.2156. Anal. Calcd
for C22H28O2: C, 81.44; H, 8.70. Found: C, 81.28; H 8.62.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith Br om oben zen e
(Ta ble 1, en tr y 6). Phosphinite ligand 3b used. Column
chromatography (CHCl3/hexane, 1:3) gave 6f (189 mg, 84%)
and 7f (24 mg, 8%, impure).
3-ter t-Bu tyl-biph en yl-2-ol (6f). Colorless oil; Rf 0.62 (CHCl3/
1
hexane, 1:3); H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 5.48
(s, 1H), 6.96 (apparent t (dd), J ) 7.7 Hz, 1H), 7.12 (dd, J )
7.5, 1.7 Hz, 1H), 7.34 (dd, J ) 7.8 Hz, 1.7 Hz, 1H), 7.49 (m,
5H); 13C NMR (75.5 MHz, CDCl3) δ 29.6, 34.9, 119.8, 126.6,
127.9, 128.0, 128.8, 129.4, 129.5, 136.2, 137.2, 150.1; HRMS
(CI) calcd for C16H19O [M+ + H] 227.1436, found 227.1425.
Anal. Calcd for C16H18O: C, 84.91; H, 8.02. Found: C, 85.29;
H, 7.70.
Cou plin g of 2-ter t-Bu tylph en ol with 4-Br om oacetoph e-
n on e (Ta ble 1, en tr y 2). Phosphinite ligand 3b used.
3-ter t-Bu tyl-4′-a cetyl-bip h en yl-2-ol (6b). Colorless solid,
257 mg (96%); Rf 0.11 (CHCl3/hexane, 1:1); 1H NMR (300 MHz,
CDCl3) δ 1.45 (s, 9H), 2.65 (s, 3H), 5.37 (s, 1H), 6.95 (apparent
t (dd), J ) 7.6 Hz, 1H), 7.09 (dd, J ) 7.5, 1.7 Hz, 1H), 7.34
(dd, J ) 7.7, 1.7 Hz, 1H), 7.58 (d, J ) 8.6 Hz, 2H), 8.08 (d, J
) 8.6 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 26.7, 29.6, 34.9,
120.2, 127.3, 127.8, 127.8, 129.3, 129.8, 136.3, 136.7, 142.5,
150.9, 197.6; HRMS (CI) calcd for C18H21O2 [M+ + H ]
269.1541, found 269.1543. Anal. Calcd for C18H20O2: C, 80.56;
H, 7.51. Found: C, 80.26; H, 7.31.
3-ter t-Bu tyl-[1,1′;2′,1′′]ter p h en yl-2-ol (7f). Colorless oil;
Rf 0.46 (CHCl3/hexane, 1:3); 1H NMR (300 MHz, CDCl3) δ 1.25
(s, 9H), 4.95 (s, 1H), 6.81 (apparent t (dd), J ) 7.6 Hz, 1H),
6.96 (dd, J ) 7.5, 1.7 Hz, 1H), 7.17 (m, 5H), 7.50 (m, 4H); 13
C
NMR (75.5 MHz, CDCl3) δ ) 29.3, 34.6, 119.6, 126.1, 126.9,
127.9, 128.2, 128.3, 128.6, 128.7, 128.9, 130.6, 131.7, 135.3,
136.0, 140.2, 141.8, 150.8; HRMS (CI) calcd for C22H23O [M+
+ H] 303.1749, found 303.1744.
Cou p lin g of 2,4-Di-ter t-bu tylp h en ol w ith 4-Br om oa n i-
sole (Ta ble 1, en tr y 3). Phosphinite ligand 3a used.
Cou p lin g of 2-Bu tylp h en ol w ith 4-Br om o-N,N-d im eth -
yla n ilin e (Ta ble 1, en tr y 7). Phosphinite ligand 3b used.
3-ter t-Bu tyl-4′-(dim eth ylam in o)-biph en yl-2-ol (6g). Light-
sensitive, colorless oil, 232 mg (86%); Rf 0.35 (CHCl3/hexane,
3,5-Di-ter t-bu tyl-4′-m eth oxy-bip h en yl-2-ol (6c). Color-
less solid, 270 mg (87%); Rf 0.27 (CHCl3/hexane, 1:2); 1H NMR
(300 MHz, CDCl3) δ 1.35 (s, 9H), 1.47 (s, 9H), 3.88 (s, 3H),
5.32 (s, 1H), 7.05 (d, J ) 8.8 Hz, 2H), 7.09 (d, J ) 2.3 Hz, 1H),
7.34 (d, J ) 2.3 Hz, 1H), 7.41 (d, J ) 8.8 Hz, 2H); 13C NMR
(75.5 MHz, CDCl3) δ 28.3, 30.2, 32.9, 33.7, 53.9, 113.4, 122.1,
123.4, 126.2, 128.4, 129.4, 133.8, 140.5, 147.4, 157.9; HRMS
(CI) calcd for C21H29O2 [M+ + H] 313.2167, found 313.2161.
Anal. Calcd for C21H28O2: C, 80.73; H, 9.03. Found: C, 80.53;
H, 8.98.
1
1:1); H NMR (300 MHz, CDCl3) δ 1.54 (s, 9H), 3.07 (s, 6H),
5.67 (s, 1H), 6.90 (d, J ) 8.9 Hz, 2H), 6.93 (apparent t (dd), J
) 7.7 Hz, 1H), 7.15 (dd, J ) 7.5, 1.7 Hz, 1H), 7.34 (dd, J )
7.8, 1.7 Hz, 1H), 7.40 (d, J ) 8.9 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 29.6, 34.9, 40.4, 113.1, 119.6, 124.3, 125.8, 128.0,
129.0, 130.2, 135.7, 150.1, 151.3; HRMS (CI) calcd for C18H24
-
-
NO [M+ + H] 270.1858, found 270.1852. Anal. Calcd for C18H23
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 4-Br om oa n isole
(Ta ble 1, en tr y 4). Phosphinite ligand 3b used.
NO: C, 80.26; H, 8.61; N, 5.21. Found: C, 80.36; H, 9.21; N,
5.07.
3-ter t-Bu tyl-4′-m eth oxy-biph en yl-2-ol (6d). Colorless solid,
202 mg (78%); Rf 0.41 (CHCl3/hexane, 1:2); 1H NMR (300 MHz,
CDCl3) δ 1.47 (s, 9H), 3.88 (s, 3H), 5.46 (s, 1H), 6.92 (apparent
t (dd), J ) 7.6 Hz, 1H), 7.05 (d, J ) 8.6 Hz, 2H), 7.08 (dd, J )
7.5, 1.7 Hz, 1H), 7.34 (dd, J ) 7.8, 1.7 Hz, 1H), 7.40 (d, J )
8.6 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 29.6, 34.9, 55.3,
114.8, 119.7, 126.3, 128.0, 128.4, 129.2, 130.7, 136.0, 151.1,
159.4; HRMS (CI) calcd for C17H21O2 [M+ + H] 257.1541, found
257.1527. Anal. Calcd for C17H20O2: C, 79.65; H, 7.86. Found:
C, 79.42; H, 7.62.
Cou p lin g of 2,4-Di-ter t-bu tylp h en ol w ith Br om oben -
zen e (Ta ble 1, en tr y 5). Phosphinite ligand 3a used. Column
chromatography (CHCl3/hexane, 1:3) gave 6e (228 mg, 80%),
7e (21 mg, 6%, impure), and 8e (22 mg, 5%, impure).
3,5-Di-ter t-bu tyl-bip h en yl-2-ol (6e). Colorless oil; Rf 0.68
(CHCl3/hexane, 1:3); 1H NMR (300 MHz, CDCl3) δ 1.42 (s, 9H),
1.54 (s, 9H), 5.39 (s, 1H), 7.17 (d, J ) 2.4 Hz, 1H), 7.43 (d, J
) 2.4 Hz, 1H), 7.52 (m, 5H); 13C NMR (75.5 MHz, CDCl3) δ
30.2, 32.1, 34.6, 35.4, 124.6, 125.2, 128.3, 128.5, 129.9, 130.1,
135.8, 138.5, 142.5, 149.1; HRMS (CI) calcd for C20H27O [M+
+ H] 283.2062, found 283.2061. Anal. Calcd for C20H26O: C,
85.06; H, 9.28. Found C, 84.70; H, 9.73.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 4-Br om ostyr en e
(Ta ble 1, en tr y 8). Phosphinite ligand 3b used. Column
chromatography (CHCl3/hexane, 1:4) gave 6h (194 mg, 75%)
and 7h (18 mg, 5%, impure).
3-ter t-Bu tyl-4′-vin yl-bip h en yl-2-ol (6h ). Colorless solid;
Rf 0.58 (CHCl3/hexane, 1:4); 1H NMR (300 MHz, CDCl3) δ 1.45
(s, 9H), 5.33 (dd, J ) 10.9, 0.8 Hz, 1H), 5.44 (d, J ) 0.5 Hz,
1H), 5.83 (dd, J ) 17.7, 0.8 Hz, 1H), 6.78 (dd, J ) 17.7, 10.9
Hz, 1H), 6.93 (apparent t (dd), J ) 7.7 Hz, 1H), 7.09 (dd, J )
7.5, 1.7 Hz, 1H), 7.31 (ddd, J ) 7.8, 1.7, 0.5 Hz, 1H), 7.43 (d,
J ) 8.3 Hz, 2H), 7.55 (d, J ) 8.3 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 29.6, 34.9, 114.6, 119.9, 126.6, 127.2, 127.9, 128.4,
129.7, 136.1, 136.2, 136.6, 137.2, 151.1; HRMS (CI) calcd for
C
C
18H21O [M+ + H] 253.1592, found 253.1583. Anal. Calcd for
18H20O: C, 85.67; H, 7.99. Found: C, 85.84; H 8.27.
3-ter t-Bu tyl-4′,4′′-d ivin yl-[1,1′;2′,1′′]ter p h en yl-2-ol (7h ).
Colorless solid; Rf 0.32 (CHCl3/hexane, 1:4); 1H NMR (300
MHz, CDCl3) δ 1.25 (s, 9H), 4.95 (d, J ) 0.6 Hz, 1H), 5.20 (dd,
J ) 10.9, 0.9 Hz, 1H), 5.36 (dd, J ) 10.9, 0.8 Hz, 1H), 5.69
(dd, J ) 17.6, 0.9 Hz, 1H), 5.87 (dd, J ) 17.6, 0.8 Hz, 1H),
6.64 (dd, J ) 17.6, 10.9 Hz, 1H), 6.80 (apparent t (dd), J ) 7.7
Hz, 1H), 6.81 (ddd, J ) 17.6, 10.9, 0.3 Hz, 1H), 6.94 (dd, J )
8678 J . Org. Chem., Vol. 68, No. 22, 2003

Catalytic Ortho-Arylation of Phenols
7.5, 1.7 Hz, 1H), 7.10 (d, J ) 8.2 Hz, 2H), 7.18 (ddd, J ) 7.7,
1.7, 0.6 Hz, 1H), 7.24 (dd, J ) 8.2, 0.5 Hz, 2H), 7.42 (ddd, J )
7.7, 0.5, 0.3 Hz, 1H), 7.52 (dd, J ) 7.7, 1.8 Hz, 1H), 7.42 (ddd,
J ) 1.8, 0.5, 0.5 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 29.3,
34.6, 113.8, 115.0, 119.7, 125.8, 125.8, 126.2, 128.0, 128.4,
128.5, 129.0, 131.9, 134.7, 136.1, 136.1, 136.3, 136.4, 138.0,
139.6, 141.6, 150.9; HRMS (CI) calcd for C26H27O [M+ + H]
355.2062, found 355.2055.
3-ter t-Bu tyl-4′-ch lor o-bip h en yl-2-ol (6n ). Colorless solid;
Rf 0.61 (CHCl3/hexane, 1:5); 1H NMR (300 MHz, CDCl3) δ 1.45
(s, 9H), 5.27 (d, J ) 0.5 Hz, 1H), 6.93 (apparent t (dd), J ) 7.7
Hz, 1H), 7.05 (dd, J ) 7.5, 1.7 Hz, 1H), 7.32 (ddd, J ) 7.8, 1.7,
0.6 Hz, 1H), 7.40 (d, J ) 8.7 Hz, 2H), 7.48 (d, J ) 8.7 Hz, 2H);
13C NMR (75.5 MHz, CDCl3) δ 29.6, 34.9, 120.1, 126.9, 127.6,
127.9, 129.6, 130.9, 134.1, 135.7, 136.4, 150.9; HRMS (CI) calcd
for C16H18ClO [M+ 37/35Cl) + H] 263.1038/261.1046, found
(
263.1038/261.1038. Anal. Calcd for C16H17ClO: C, 73.70; H,
6.57. Found: C, 73.79; H, 6.66.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 3-Br om oa n isole
(Ta ble 1, en tr y 9). Phosphinite ligand 3b used.
3,3′′-Di-ter t-bu tyl-[1,1′;4′,1′′]ter p h en yl-2,2′′-d iol (9). Col-
orless solid; Rf 0.23 (CHCl3/hexane, 1:5); H NMR (300 MHz,
3-ter t-Bu tyl-3′-m eth oxy-bip h en yl-2-ol (6i). Colorless oil,
256 mg (100%); Rf 0.39 (CHCl3/hexane, 1:2); 1H NMR (300
MHz, CDCl3) δ 1.47 (s, 9H), 3.86 (s, 3H), 5.59 (d, J ) 0.5 Hz,
1H), 6.94 (dd, J ) 7.8, 7.5 Hz, 1H), 6.97 (ddd, J ) 8.1, 2.6, 0.9
Hz, 1H), 6.99 (ddd, J ) 2.6, 0.9, 0.8 Hz, 1H), 7.05 (ddd, J )
7.5, 1.5, 0.9 Hz, 1H), 7.11 (dd, J ) 7.5, 1.7 Hz, 1H), 7.32 (ddd,
J ) 7.8, 1.7, 0.5 Hz, 1H), 7.43 (ddd, J ) 8.1, 7.5, 0.8 Hz, 1H);
13C NMR (75.5 MHz, CDCl3) δ 29.6, 34.9, 55.3, 113.7, 114.9,
119.8, 121.5, 126.6, 127.7, 128.6, 130.5, 136.2, 138.6, 151.0,
160.4; HRMS (CI) calcd for C17H21O2 [M+ + H] 257.1541, found
257.1535. Anal. Calcd for C17H20O2: C, 79.65; H, 7.86. Found:
C, 79.47; H, 8.19.
1
CDCl3) δ 1.46 (s, 18H), 5.44 (s, 2H), 6.96 (apparent t (dd), J )
7.7 Hz, 2H), 7.13 (dd, J ) 7.5, 1.7 Hz, 2H), 7.32 (dd, J ) 7.7,
1.7 Hz, 2H), 7.60 (s, 4H); 13CNMR (75.5 MHz, CDCl3) δ 29.6,
34.7, 120.1, 126.9, 128.0, 128.1, 130.6, 136.4, 137.0, 151.0;
HRMS (CI) calcd for C26H31O2 [M+ + H] 375.2324, found
375.2309.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 2-Br om op yr id in e
(Ta ble 1, en tr y 15). Phosphinite ligand 3b used.
2-ter t-Bu tyl-6-p yr id in e-2-yl-p h en ol (6o). Sticky, pale
yellow solid, 52 mg (23%); Rf 0.53 (CHCl3/hexane, 1:3); 1H NMR
(300 MHz, CDCl3) δ 1.51 (s, 9H), 6.87 (apparent t (dd), J )
7.9 Hz, 1H), 7.22 (ddd, J ) 7.4, 5.0, 1.1 Hz, 1H), 7.36 (dd, J )
7.7, 1.6 Hz, 1H), 7.70 (ddd, J ) 8.0, 1.6, 0.4 Hz, 1H), 7.81 (ddd,
J ) 8.4, 7.4, 1.9 Hz, 1H), 7.92 (dddd, J ) 8.4, 1.1, 1.0, 0.4 Hz,
1H), 8.39 (ddd, J ) 5.0, 1.9, 1.0 Hz, 1H), 15.01 (s, 1H); 13C
NMR (75.5 MHz, CDCl3) δ 29.5, 35.0, 117.8, 118.6; 119.6,
121.1, 124.4, 128.6, 137.7, 138.4, 145.2, 158.5, 159.3; HRMS
(CI) calcd for C15H18NO [M+ + H] 228.1388, found 228.1386.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 2-Br om oa n isole
(Ta ble 1, en tr y 10). Phosphinite ligand 3b used.
3-ter t-Bu tyl-2′-m eth oxy-bip h en yl-2-ol (6j). Colorless oil,
256 mg (100%); Rf 0.40 (CHCl3/hexane, 1:2); 1H NMR (300
MHz, CDCl3) δ 1.50 (s, 9H), 3.90 (s, 3H), 6.16 (d, J ) 0.5 Hz,
1H), 6.98 (apparent t (dd), J ) 7.7 Hz, 1H), 7.07 (ddd, J ) 8.2,
1.1, 0.3 Hz, 1H), 7.13 (ddd, J ) 7.5, 7.5, 1.1 Hz, 1H), 7.14 (dd,
J ) 7.5, 1.6 Hz, 1H), 7.36 (ddd, J ) 7.5, 1.8, 0.3 Hz, 1H), 7.36
(ddd, J ) 7.8, 1.6, 0.5 Hz, 1H), 7.42 (ddd, J ) 8.2, 7.5, 1.8 Hz,
1H); 13C NMR (75.5 MHz, CDCl3) δ 29.7, 35.0, 56.0, 111.4,
120.1, 122.0, 126.5, 127.0, 127.1, 129.2, 129.3, 132.7, 137.4,
152.3, 155.7; HRMS (CI) calcd for C17H21O2 [M+ + H] 257.1541,
found 257.1522. Anal. Calcd for C17H20O2: C, 79.65; H, 7.86.
Found: C, 79.55; H, 8.23.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 3-Br om op yr id in e
(Ta ble 1, en tr y 16). Phosphinite ligand 3b used. Column
chromatography (NEt3/ethyl acetate/hexane, 1:4:5) gave 6p (93
mg, 41%) and 7p (33 mg, 11%, impure).
2-ter t-Bu tyl-6-p yr id in e-3-yl-p h en ol (6p ). Yellow solid; Rf
0.83 (NEt3/ethyl acetate/hexane, 1:4:5; recrystallized from CH2-
1
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 2-Br om o-p-xylen e
(Ta ble 1, en tr y 11). Phosphinite ligand 3b used.
Cl2/hexane); H NMR (300 MHz, CDCl3) δ 1.47 (s, 9H), 6.29
(s, br, 1H), 6.96 (apparent t (dd), J ) 7.6 Hz, 1H), 7.03 (dd, J
) 7.5, 1.9 Hz, 1H), 7.35 (ddd, J ) 7.9, 4.9, 0.9 Hz, 1H), 7.36
(dd, J ) 7.7, 1.9 Hz, 1H), 7.82 (ddd, J ) 7.9, 2.3, 1.7 Hz, 1H),
8.43 (dd, J ) 4.9, 1.9 Hz, 1H), 8.50 (dd, J ) 2.3, 0.9 Hz, 1H);
13C NMR (75.5 MHz, CDCl3) δ 29.7, 35.0, 120.3, 123.6, 126.0,
127.4, 128.2, 134.2, 137.5, 137.6, 148.2, 150.0, 151.8; HRMS
(CI) calcd for C15H18NO [M+ + H] 228.1388, found 228.1389.
Anal. Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found:
C, 79.32; H, 7.76; N, 5.96.
3-ter t-Bu tyl-2′,5′-d im eth yl-bip h en yl-2-ol (6k ). Colorless
1
oil, 254 mg (100%); (CHCl3/hexane, 1:4); H NMR (300 MHz,
CDCl3) δ 1.49 (s, 9H), 2.15 (s, 3H), 2.40 (s, 3H), 5.02 (d, J HH
)
0.6 Hz, 1H), 6.94 (apparent t (dd), J ) 7.5 Hz, 1H), 7.01 (dd,
J ) 7.4, 1.9 Hz, 1H), 7.14 (d, J ) 1.9 Hz, 1H), 7.18 (dd, J )
7.7, 1.9 Hz, 1H), 7.27 (d, J ) 7.7 Hz, 1H), 7.34 (ddd, J ) 7.6,
1.9, 0.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ ) 19.2, 20.9,
29.56, 34.5, 119.5, 126.2, 127.6, 128.4, 129.3, 130.6, 131.4,
134.4, 135.6, 135.8, 136.2, 151.0; HRMS (CI) calcd for C18H23
O
2-[3,4′]-Bip yr id in yl-3′-yl-6-ter t-bu tyl-p h en ol (7p ). Pale
yellow oil; Rf 0.24 (NEt3/ethyl acetate/hexane, 1:4:5); 1H NMR
(300 MHz, CDCl3) δ 1.24 (s, 9H), 5.80 (d, br, 1H), 6.89
(apparent t (dd), J ) 7.6 Hz, 1H), 6.97 (dd, J ) 7.5, 1.7 Hz,
1H), 7.11 (ddd, J ) 7.9, 4.9, 0.8 Hz, 1H), 7.25 (dd, J ) 7.7, 1.7
Hz, 1H), 7.38 (dd, J ) 5.0, 0.7 Hz, 1H), 7.39 (ddd, J ) 7.9, 2.3,
1.6 Hz, 1H), 8.40 (dd, J ) 2.3, 0.8 Hz, 1H), 8.45 (dd, J ) 4.9,
1.6 Hz, 1H), 8.56 (m, br, 1H), 8.61 (m, br, 1H); 13C NMR (75.5
MHz, CDCl3) δ 29.3, 34.6, 120.5, 122.8, 123.9, 124.4, 127.4,
128.6, 133.8, 135.6, 137.4, 146.1, 149.0, 149.1, 149.6, 151.3,
151.9; HRMS (CI) calcd for C20H21N2O [M+ + H] 305.1654,
found 305.1646.
Cou plin g of 2-ter t-Bu tylph en ol with 3-Br om oth ioph en e
(Ta ble 1, en tr y 17). Phosphinite ligand 3b used. Column
chromatography (CHCl3/hexane, 1:4) gave 6q (30 mg, 13%,
impure), 7q (108 mg, 34%), and 8q (102 mg, 26%).
2-ter t-Bu tyl-6-th iop h en e-3-yl-p h en ol (6q). Colorless oil;
Rf 0.60 (CHCl3/hexane, 1:4); 1H NMR (300 MHz, CDCl3) δ 1.44
(s, 9H), 5.62 (s, 1H), 6.90 (dd, J ) 7.9, 7.5 Hz, 1H), 7.13 (dd, J
) 7.5, 1.7 Hz, 1H), 7.21 (dd, J ) 4.9, 1.3 Hz, 1H), 7.28 (dd, J
) 7.9, 1.7 Hz, 1H), 7.42 (dd, J ) 3.0, 1.3 Hz, 1H), 7.52 (dd, J
) 4.9, 3.0 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 29.5, 34.9,
119.8, 123.3, 123.6, 126.6, 127.5, 127.7, 128.7, 136.2, 137.6,
151.4; HRMS (CI) calcd for C14H17OS [M+ + H] 233.1000, found
233.1009.
[M+ + H] 255.1749, found 255.1750 Anal. Calcd for C18H22O:
C, 84.99; H, 8.72. Found: C, 84.69; H, 9.01.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 1-Br om on a p h -
th a len e (Ta ble 1, en tr y 12). Phosphinite ligand 3b used.
2-ter t-Bu t yl-6-n a p h t h a len e-1-yl-p h en ol (6m ). Light-
sensitive, colorless oil, 255 mg (92%); Rf 0.51 (CHCl3/hexane,
1
1:3); H NMR (300 MHz, CDCl3) δ 1.48 (s, 9H), 5.01 (d, J )
0.6 Hz, 1H), 7.00 (dd, J ) 7.8, 7.4 Hz, 1H), 7.13 (dd, J ) 7.4,
1.7 Hz, 1H), 7.41 (ddd, J ) 7.8, 1.7, 0.6 Hz, 1H), 7.47 (ddd, J
) 8.2, 7.0, 1.4 Hz, 1H), 7.54 (dd, J ) 6.9, 1.4 Hz, 1H), 7.55
(ddd, J ) 8.0, 6.8, 1.4 Hz, 1H), 7.60 (dd, J ) 8.2, 7.0 Hz), 1H,
7.66 (d, br, J ) 8.2 Hz, 1H), 7.95 (m, 2H); 13C NMR (75.5 MHz,
CDCl3) δ ) 29.6, 34.9, 119.6, 125.2, 125.8, 126.4, 126.7, 126.7,
126.7, 128.4, 128.6, 128.8, 128.9, 132.1, 134.0, 134.1, 136.2,
151.7; HRMS (CI) calcd for C22H21O [M+ + H] 277.1592, found
277.1587. Anal. Calcd for C22H20O: C, 86.92; H 7.29. Found:
C, 86.85; H 7.71.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 4-Ch lor oa n isole
(Ta ble 1, en tr y 13). Phosphinite ligand 3b used. Compound
6d , 38 mg (15%). Data as above.
Cou p lin g of 2-ter t-Bu t ylp h en ol w it h 4-Ch lor ob r o-
m oben zen e (Ta ble 1, en tr y 14). Phosphinite ligand 3b used.
Column chromatography (CHCl3/hexane, 1:5) gave 6n (68 mg,
26%) and 9 (22 mg, 6%, impure).
J . Org. Chem, Vol. 68, No. 22, 2003 8679

Bedford and Limmert
2-[2,3′]Bith iop h en yl-3-yl-6-ter t-bu tyl-p h en ol (7q). Yel-
low oil; Rf 0.49 (CHCl3/hexane, 1:4); 1H NMR (300 MHz, CDCl3)
δ 1.38 (s, 9H), 5.30 (s, 1H), 6.92 (dd, J ) 7.8, 7.5 Hz, 1H), 6.97
(dd, J ) 5.0, 1.4 Hz, 1H), 7.04 (d, J ) 5.1 Hz, 1H), 7.07 (dd, J
) 3.0, 1.4 Hz, 1H), 7.08 (dd, J ) 7.5, 1.7 Hz, 1H), 7.20 (dd, J
) 5.0, 3.0 Hz, 1H), 7.32 (dd, J ) 7.8, 1.7 Hz, 1H), 7.35 (d, J )
5.1 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 29.5, 34.9, 120.0,
121.7, 123.6, 124.5, 125.8, 126.8, 126.8, 128.0, 131.3, 132.1,
133.6, 135.9, 136.3, 151.5; HRMS (CI) calcd for C18H19OS2 [M+
+ H] 315.0877, found 315.0857. Anal. Calcd for C18H18OS2: C,
68.75; H, 5.77. Found: C, 68.71; H 5.98.
2-ter t-Bu tyl-6-[3,2′;4′,3′′]ter th iop h en e-3′-yl-p h en ol (8q).
Yellow solid; Rf 0.33 (CHCl3/hexane, 1:4); 1H NMR (300 MHz,
CDCl3) δ 1.38 (s, 9H), 5.22 (d, J ) 0.5 Hz, 1H), 6.80 (dd, J )
3.0, 1.3 Hz, 1H), 6.88 (apparent t (dd), J ) 7.4 Hz, 1H), 6.93
(dd, J ) 7.4, 2.0 Hz, 1H), 6.99 (dd, J ) 5.0, 1.4 Hz, 1H), 7.00
(dd, J ) 5.0, 1.3 Hz, 1H), 7.01 (dd, J ) 3.0, 1.4 Hz, 1H), 7.18
(dd, J ) 5.0, 3.0 Hz, 1H), 7.20 (dd, J ) 5.0, 3.0 Hz, 1H), 7.35
(ddd, J ) 7.4, 2.0, 0.5 Hz, 1H), 7.42 (s, 1H); 13C NMR (75.5
MHz, CDCl3) δ 29.3, 34.7, 120.4, 120.7, 121.3, 121.8, 123.4,
125.0, 125.6, 126.9, 127.1, 127.2, 128.7, 130.2, 133.9, 135.9,
136.5, 138.2, 138.4, 152.2; HRMS (CI) calcd for C22H21OS3 [M+
+ H] 397.0754, found 397.0727. Anal. Calcd for C22H20OS3: C,
66.63; H, 5.08. Found: C, 66.82; H 4.96.
Cou p lin g of 2-Met h ylp h en ol w it h 4-Br om oa n isole
(Ta ble 1, en tr y 21). Phosphinite ligand 3b used. Column
chromatography (MeOH/CHCl3/hexane, 0.1:1:4) gave 6u (21%).
Compound 7u observed in impure product mixture (∼5% by
1H NMR, not isolated; see below for data, Table 3, entry 12).
4′-Meth oxy-3-m eth yl-bip h en yl-2-ol (6u ). Colorless solid;
Rf 0.50 (MeOH/CHCl3/hexane, 0.1:1:4); 1H NMR (300 MHz,
CDCl3) δ 2.32 (s, 3H), 3.87 (s, 3H), 5.25 (s, 1H), 6.89 (apparent
t (dd), J ) 7.4 Hz, 1H), 7.03 (d, J ) 8.9 Hz, 2H), 7.06 (dd, J )
7.6, 1.7 Hz, 1H), 7.16 (dd, J ) 7.3, 1.7 Hz, 1H), 7.39 (d, J )
8.9 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 16.2, 55.3, 114.7,
120.1, 124.4, 127.3, 127.7, 129.3, 130.1, 130.3, 150.6, 159.3;
HRMS (CI) calcd for C14H15O2 [M+ + H] 215.1072, found
215.1087. Anal. Calcd for C14H14O2: C, 78.48; H, 6.59. Found:
C, 78.56; H, 6.50.
Cou p lin g of 2-Na p h th ol w ith 4-Br om oa cetop h en on e
(Ta ble 1, en tr y 22). Phosphinite ligand 3c used. Column
chromatography ((MeOH/CHCl3, 1:99) gave 6v (102 mg, 39%)
and 10v (∼1:1 mixture with 6v, ∼13%).
2-(4-Acetyl-p h en yl)-n a p h th a len e-1-ol (6v). Light-sensi-
tive, colorless solid; Rf 0.33 (MeOH/CHCl3, 1:99); 1H NMR (300
MHz, CDCl3) δ 2.67 (s, 3H), 5.83 (s, 1H), 7.36 (d, J ) 8.4 Hz,
1H), 7.52 (d, br, J ) 8.4 Hz,1H), 7.53 (m, 1H), 7.54 (m, 1H),
7.68 (d, J ) 8.6 Hz, 2H), 7.54 (m, 1H), 8.12 (d, J ) 8.6 Hz,
2H), 8.30 (m, 1H); 13C NMR (75.5 MHz, CDCl3) δ 26.7, 120.2,
120.6 122.3, 124.4, 125.8, 126.9, 127.0, 127.6, 129.5, 129.5,
134.4, 136.2, 142.6, 147.9, 197.6; HRMS (CI) calcd for C18H15O2
[M+ + H] 263.1072, found 263.1067. Anal. Calcd for C18H14O2:
C, 82.42; H, 5.38. Found: C, 82.50; H, 5.25.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 3-Br om o-4-m eth -
ylth iop h en e (Ta ble 1, en tr y 18). Phosphinite ligand 3b
used. Column chromatography (CHCl3/hexane, 1:4) gave 6r
(65 mg, 26%, impure) and 7r (mixture with 6r , ∼8%).
2-ter t-Bu t yl-6-(4-m et h yl-t h iop h en e-3-yl)-p h en ol (6r ).
Colorless oil; Rf 0.59 (CHCl3/hexane, 1:4); 1H NMR (300 MHz,
CDCl3) δ 1.45 (s, 9H), 2.11 (dd, J ) 1.0, 0.3 Hz, 3H), 5.28 (s,
br, 1H), 6.90 (apparent t (dd); J ) 7.7 Hz, 1H), 7.01 (dd, J )
7.5, 1.8 Hz, 1H), 7.15 (dq, J ) 3.2, 1.0 Hz, 1H), 7.30 (dd, J )
3.2, 0.3 Hz, 1H), 7.31 (dd, J ) 7.8, 1.8 Hz, 1H); 13C NMR (75.5
MHz, CDCl3) δ 14.6, 29.5, 34.8, 119.4, 123.0, 123.4, 125.1,
126.7, 128.1, 136.0, 137.3, 137.7, 151.8; HRMS (CI) calcd for
2,8-Bis(4-acetyl-ph en yl)-1-n aph th alen e-1-ol (10v). Light-
sensitive, red substance; Rf 0.33 (MeOH/CHCl3, 1:99); 1H NMR
(300 MHz, CDCl3) δ 2.61 (s, 3H), 2.65 (s, 3H), 5.46 (s, 1H),
7.26 (dd, 1H, J ) ∼7, 1.2 Hz), 7.46 (d, 1H, J ) 8.4 Hz), 7.52
3
(m, 1H), 7.60 (d, 2H, J ) 8.6 Hz), 7.61 (d, 2H, J HH ) 8.4 Hz),
7.62 (d, 2H, J ) 8.7 Hz), 7.91 (dd, 1H, J ) 8.4, 1.2 Hz), 8.01
(d, 2H, J ) 8.7 Hz), 8.04 (d, 2H, J ) 8.6 Hz); HRMS (CI) calcd
for C26H20O3 [M+ + H] 381.1490, found 381.1477.
C
15H19OS [M+ + H] 247.1156, found 247.1154.
2-ter t-Bu t yl-6-(4,4′-d im et h yl-[2,3′]b it h iop h en yl-3-yl)-
Com petitive Cou plin g of 4-ter t-Bu tylph en ol with 4-Br o-
m otolu en e a n d 4-Br om o-N, N-d im eth yla n ilin e (eq 1). In
a Radleys reaction tube under nitrogen were added [RhCl-
(PPh3)3] (46 mg, 0.05 mmol), toluene (10 mL), 4-bromotoluene
(0.255 g, 1.5 mmol), 4-bromo-N,N-dimethylaniline (0.3000 g,
1.5 mmol), 3b (0.037 g, 0.15 mmol), 2-tert-butylphenol (0.150
g, 1.0 mmol), and Cs2CO3 (0.550 g, 1.70 mmol). The mixture
was heated at reflux temperature for 18 h and allowed to cool,
and then HCl (aq) (2 M, 5 mL) was added. The organic phase
was extracted with dichloromethane (3 × 25 mL), and a
solution of 1,3,5-trimethoxybenzene (0.333 M in toluene, 1.00
mL, 1H NMR standard) was added. The solution was dried
(MgSO4) and filtered, and the solvent was removed under
reduced pressure. A sample in CDCl3 was taken without
further treatment from the crude reaction mixture, and the
conversion to 6w and 6f was determined by 1H NMR spec-
troscopy.
p h en ol (7r ). Colorless oil; Rf 0.50 (CHCl3/hexane, 1:4); 1H
NMR (300 MHz, CDCl3) δ 1.34 (s, 9H), 2.03 (dd, J ) 1.1, 0.4
Hz, 3H), 2.10 (d, J ) 1.0 Hz, 3H), 5.18 (d, J ) 0.6 Hz, 1H),
6.80 (apparent t (dd), J ) 7.5 Hz, 1H), 6.84 (dq, J ) 3.3, 1.0
Hz, 1H), 6.86 (dd, J ) 6.86, 2.0 Hz, 1H), 7.05 (dd, J ) 3.3, 0.4
Hz, 1H), 7.12 (q, J ) 1.1 Hz, 1H), (ddd, J ) 7.5, 2.0, 0.6 Hz,
1H); 13C NMR (75.5 MHz, CDCl3) δ 15.3, 15.4, 29.3, 34.6, 119.6,
121.5, 121.5, 123.0, 125.4, 126.4, 128.5, 134.0, 134.8, 136.0,
136.4, 136.7, 138.1, 151.7; HRMS (CI) calcd for C20H23OS2 [M+
+ H] 343.1190, found 343.1187.
Cou p lin g of 2-Isop r op ylp h en ol w ith 4-Br om oa n isole
(Ta ble 1, en tr y 19). Phosphinite ligand 3b used.
3-Isopr opyl-4′-m eth oxy-biph en yl-2-ol (6s). Colorless solid,
165/166 mg (68%); Rf 0.65 (CHCl3); 1H NMR (300 MHz, CDCl3)
δ 1.31 (d, J ) 6.9 Hz, 6H), 3.37 (sept., J ) 6.9 Hz, 1H), 3.88 (s,
3H), 5.30 (s, 1H), 6.97 (apparent t (dd), J ) 7.6 Hz, 1H), 7.04
(d, J ) 8.8 Hz, 2H), 7.07 (dd, J ) 7.5, 1.7 Hz, 1H), 7.24 (dd, J
) 7.7, 1.7 Hz, 1H), 7.41 (d, J ) 8.8 Hz, 2H); 13C NMR (75.5
MHz, CDCl3) δ 22.6, 27.2, 55.3, 114.8, 120.3, 125.5, 127.5,
127.5, 129.4, 130.4, 134.8, 149.7, 159.3; HRMS (CI) calcd for
Effect of Va r yin g Con d ition s a n d Liga n d s on th e
Or th o-Ar yla tion Rea ction (Ta ble 2). In a Radleys reaction
tube under nitrogen were added the appropriate amount of
[{RhCl(COD)}2], toluene (10 mL), the 4-bromoanisole (0.19 mL,
1.5 mmol), the appropriate amount of 3d , the appropriate
amount of phosphine co-ligand, 2-isoproylphenol (0.136 g, 1.0
mmol), and base (1.70 mmol). The mixture was heated at reflux
temperature for 18 h and allowed to cool, and then HCl (aq)
(2 M, 5 mL) was added. The organic phase was extracted with
dichloromethane (3 × 25 mL), and a solution of 1,3,5-tri-
methoxybenzene (0.333 M in toluene, 1.00 mL, 1H NMR
standard) was added. The solution was dried (MgSO4) and
filtered, and the solvent was removed under reduced pressure.
A sample in CDCl3 was taken without further treatment from
the crude reaction mixture, and the conversion to 6s was
C
C
16H19O2 [M+ + H] 243.1380, found 243.1383. Anal. Calcd for
16H18O2: C, 79.31; H, 7.49. Found: C, 79.41; H, 7.72.
Cou plin g of 2-Eth ylph en ol with 4-Br om oan isole (Table
1, en tr y 20). Phosphinite ligand 3b used.
3-Eth yl-4′-m eth oxy-bip h en yl-2-ol (6t). Colorless solid,
121/176 mg (53%); Rf 0.56 (CHCl3); 1H NMR (300 MHz, CDCl3)
δ 1.28 (t, J ) 7.5 Hz, 3H), 3.37 (q, J ) 7.5 Hz, 2H), 3.87 (s,
3H), 5.25 (s, 1H), 6.92 (apparent t (dd), J ) 7.5 Hz, 1H), 7.03
(d, J ) 8.8 Hz, 2H), 7.07 (dd, J ) 7.6, 1.6 Hz, 1H), 7.24 (dd, J
) 7.4, 1.6 Hz, 1H), 7.39 (d, J ) 8.8 Hz, 2H); 13C{1H} NMR
(75.5 MHz, CDCl3) δ 14.0, 23.4, 55.3, 114.7, 120.2, 127.4, 127.7,
128.4, 129.4, 130.4, 130.5, 150.3, 159.3; HRMS (CI) calcd for
1
determined by H NMR spectroscopy.
C
C
15H17O2 [M+ + H] 229.1228, found 229.1223. Anal. Calcd for
15H16O2: C, 78.92; H, 7.06. Found: C, 79.01; H, 7.15.
Gen er a l Meth od for Cou p lin g of P h en ol w ith 2-Br o-
m oa n isole w ith Va r yin g Ca ta lysts/Co-ca ta lysts (F igu r e
8680 J . Org. Chem., Vol. 68, No. 22, 2003

Catalytic Ortho-Arylation of Phenols
1). In a Radleys reaction tube under nitrogen were added the
rhodium precursor (either [RhCl(PPh3)3] or [{RhCl(COD)}2] (5
mol % Rh), toluene (10 mL), phenol (0.094 g, 1.0 mmol),
4-bromoanisole (0.19 mL, 1.5 mmol), and the appropriate
ligand (see Figure 1) (0.15 or 0.30 mmol). The mixture was
heated at reflux temperature for 18 h and allowed to cool, and
then HCl (aq) (2 M, 5 mL) was added. The organic phase was
extracted with dichloromethane (3 × 25 mL), and a solution
4′-Meth oxy-4-m eth yl-bip h en yl-2-ol (6x). Colorless solid;
Rf 0.42 (MeOH/CHCl3, 1:99); 1H NMR (300 MHz, CDCl3) δ 2.35
(s, 3H), 3.86 (s, 3H), 5.13 (s, 1H), 6.79 (dd, J ) 8.1, 1.6 Hz,
1H), 6.81 (d, J ) 1.6 Hz, 1H), 7.01 (d, J ) 8.9 Hz, 2H), 7.11 (d,
J ) 8.1 Hz, 1H), 7.38 (d, J ) 8.9 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 21.2, 55.3, 114.7, 116.2, 121.6, 124.9, 129.2, 130.0,
130.2, 139.0, 152.2, 159.1; HRMS (CI) calcd for C14H15O2 [M+
+ H] 215.1072, found 215.1073.
4,4′′-Dim eth oxy-4′-m eth yl-[1,1′;3′,1′′]ter ph en yl-2′-ol (11x).
Colorless solid; Rf 0.64 (MeOH/CHCl3, 1:99); 1H NMR (300
MHz, CDCl3) δ 2.10 (s, 3H), 3.84 (s, 3H), 3.87 (s, 3H), 5.02 (s,
1H), 6.91 (d, J ) 7.7 Hz, 1H), 6.97 (d, J ) 8.7 Hz, 2H), 7.04 (d,
J ) 8.7 Hz, 2H), 7.19 (d, J ) 7.7 Hz, 1H), 7.26 (d, J ) 8.7 Hz,
2H), 7.50 (d, J ) 8.7 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ
20.4, 55.3, 55.3, 113.9, 114.7, 121.9, 125.2, 127.5, 128.1, 129.1,
130.3, 130.4, 131.4, 136.7, 149.9, 158.7, 159.3; HRMS (CI) calcd
for C21H21O3 [M+ + H] 321.1491, found 321.1484. Anal. Calcd
for C21H20O3: C, 78.73; H, 6.29. Found: C, 78.96; H, 6.35.
Cou p lin g of 3-Meth oxyp h en ol w ith 4-Br om oa n isole
(Ta ble 3, en tr y 4). Column chromatography (MeOH/CHCl3,
1:99) gave 6y (156 mg, 68%) and 11y (92 mg, 27%).
4,4′-Dim eth oxy-bip h en yl-2-ol (6y). Colorless solid; Rf 0.21
(MeOH/CHCl3, 1:99); 1H NMR (300 MHz, CDCl3) δ 3.82 (s, 3H),
3.85 (s, 3H), 5.29 (s, 1H), 6.56 (d, J ) 2.4 Hz, 1H), 6.56 (dd, J
) 9.1, 2.4 Hz, 1H), 7.01 (d, J ) 8.8 Hz, 2H), 7.12 (d, J ) 9.1
Hz, 1H), 7.35 (d, J ) 8.8 Hz, 2H); 13C NMR (75.5 MHz, CDCl3)
δ 55.3, 55.3, 101.1, 106.8, 114.7, 120.5, 129.0, 130.2, 130.7,
153.4, 159.0, 160.2; HRMS (CI) calcd for C14H15O3 [M+ + H]
231.1021, found 231.1030. Anal. Calcd for C14H14O3: C, 73.03;
H, 6.13. Found: C, 73.34; H, 6.10.
1
of 1,3,5-trimethoxybenzene (0.333 M in toluene, 1.00 mL, H
NMR standard) was added. The solution was dried (MgSO4)
and filtered, and the solvent was removed under reduced
pressure. A sample in CDCl3 was taken without further
treatment from the crude reaction mixture, and the conver-
sions to 11a and 12 were determined by 1H NMR spectroscopy.
See below for data for these compounds.
Cou p lin g of P h en ol w ith 2-Br om o-p-xylen e (eq 2). As
above with [RhCl(PPh3)3] (5 mol %) and phosphinite 3d (15
mol %).
2,5,2′′,5′′-Tet r a m et h yl-[1,1′;3′,1′′]t er p h en yl-2′-ol (11b ).
1
Colorless oil, 103 mg (34%); Rf 0.54 (CHCl3/hexane, 1:1); H
NMR (300 MHz, CDCl3) δ 2.20 (s, 6H), 2.37 (s, 6H), 4.85 (s,
1H), 7.07 (m, 1H), 7.14 (m, br, 6H), 7.22 (m, br, 2H); 13C NMR
(75.5 MHz, CDCl3) δ 19.8, 21.4, 120.0, 128.4, 128.8, 129.7,
130.1, 130.9, 133.9, 135.5, 136.6, 149.4; HRMS (CI) calcd for
C
C
22H23O [M+ + H] 303.1749, found 303.1740. Anal. Calcd for
22H22O: C, 87.38; H, 7.33. Found: C, 87.28; H, 7.51.
Gen er a l Ca ta lytic Meth od ology for Ar yla tion of P h e-
n ols with ou t 2-Su bstitu tion an d Related Reaction s (Table
3). In a Radleys reaction tube under nitrogen were added the
[{RhCl(COD)}2] (25 mg, 0.05 mmol), toluene (10 mL), the
appropriate aryl halide (1.5 mmol), P(NMe2)3 (0.049 g, 0.30
mmol), the appropriate phenol (1.0 mmol), and Cs2CO3 (0.550
g, 1.70 mmol). The mixture was heated at reflux temperature
for 18 h and allowed to cool, and HCl (aq) (2 M, 5 mL) was
added. The organic phase was extracted with dichloromethane
(3 × 25 mL), dried (MgSO4), and filtered, and the solvent was
removed under reduced pressure. The crude mixture was then
subjected to column chromatography (silica).
Cou p lin g of P h en ol w ith 4-Br om oa n isole (Ta ble 3,
en tr y 1). Column chromatography (MeOH/CHCl3/hexane, 0.1:
1:4) gave 11a (94 mg, 31%) and 12 (∼3%, impure, contains
substantial amounts of 11a ).
4,4′′-Dim eth oxy-[1,1′;3′,1′′]ter p h en yl-2′-ol (11a ). Color-
less solid; Rf 0.23 (MeOH/CHCl3/hexane, 0.1:1:4); 1H NMR (300
MHz, CDCl3) δ 3.97 (s, 6H), 5.40 (s, 1H), 7.02 (d, J ) 8.8 Hz,
4H), 7.04 (t, J ) 7.4 Hz, 1H), 7.24 (d, J ) 7.4 Hz, 2H), 7.50 (d,
J ) 8.8 Hz, 4H); 13C NMR (75.5 MHz, CDCl3) δ 55.3, 114.2,
120.5, 128.3, 129.5, 129.8, 130.4, 149.4, 159.1; HRMS (CI) calcd
for C20H19O3 [M+ + H] 307.1334, found 307.1338. Anal. Calcd
for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.14; H, 5.74.
4,4′,4′′-Tr im eth oxy-[1,1′;3′,1′′]ter p h en yl-2′-ol (11y). Col-
orless solid; Rf 0.56 (MeOH/CHCl3, 1:99); 1H NMR (300 MHz,
CDCl3) δ 3.78 (s, 3H), 3.85 (s, 3H), 3.87 (s, 3H), 5.24 (s, 1H),
6.67 (d, J ) 8.6 Hz, 1H), 6.99 (d, J ) 8.6 Hz, 2H), 7.05 (d, J )
8.6 Hz, 2H), 7.25 (d, J ) 8.6 Hz, 1H), 7.36 (d, J ) 8.6 Hz, 2H),
7.49 (d, J ) 8.6 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 55.2,
55.3, 55.8, 103.2, 113.9, 114.4, 116.9, 121.2, 124.6, 129.5, 130.2,
130.3, 132.0, 150.5, 156.7, 158.6, 159.2; HRMS (CI) calcd for
C
C
21H21O4 [M+ + H] 337.1440, found 337.1432. Anal. Calcd for
21H20O4: C, 74.98; H, 5.99. Found: C, 75.20; H, 6.03.
Cou p lin g of 3-ter t-Bu tylp h en ol w ith 4-Br om oa n isole
(Ta ble 3, en tr y 5). 4-ter t-Bu tyl-4′-m eth oxy-bip h en yl-2-ol
(6z). Colorless solid, 100 mg (39%); Rf 0.54 (MeOH/CHCl3,
1
1:99); H NMR (300 MHz, CDCl3) δ 1.34 (s, 9H), 3.86 (s, 3H),
5.15 (s, 1H), 7.01 (dd, J ) 8.5, 1.9 Hz, 1H), 7.02 (d, J ) 8.8
Hz, 2H), 7.02 (d, J ) 1.9 Hz, 1H), 7.16 (d, J ) 8.5 Hz, 1H),
7.39 (d, J ) 8.8 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 31.3,
34.6, 55.3, 112.8, 114.7, 117.8, 124.8, 129.2, 129.7, 130.2, 152.0,
152.5, 159.1; HRMS (CI) calcd for C17H21O2 [M+ + H] 257.1542,
found 257.1540. Anal. Calcd for C17H20O2: C, 79.65; H, 7.86.
Found: C, 79.48; H, 8.02.
4,4′′,4′′′-Tr im et h oxy-[1,1′;3′,1′′;2′′,1′′′]q u a t er p h en yl-2′-
ol (12). Colorless oil; Rf 0.10 (MeOH/CHCl3/hexane, 0.1:1:4);
1H NMR (300 MHz, CDCl3) (some signals obscured by 11a
impurity) δ 3.77 (s, 3H), 3.83 (s, 3H), 3.89 (s, 3H), 5.01 (s, 1H),
6.77 (d, J ) 8.8 Hz, 2H), 6.89 (apparent t (dd), J ) 7.6 Hz,
1H), 6.94 (d, J ) 8.8 Hz, 2H), 7.14 (d, J ) 8.8 Hz, 2H), 7.16
(dd, J ) 7.5, 1.8 Hz, 1H), 7.33 (d, J ) 8.8 Hz, 2H), 7.37 (d, J
) 8.4 Hz, 1H); HRMS (CI) calcd for C27H25O4 [M+ + H]
413.1753, found 413.1741.
Cou p lin g of P h en ol w ith Br om om esitylen e (Ta ble 3,
en tr y 2). 2,4,6,2′′,4′′,6′′-Hexa m eth yl-[1,1′;3′,1′′]ter p h en yl-
2′-ol (11c). Colorless solid, 52 mg (16%); Rf 0.50 (CHCl3/
hexane, 1:1); 1H NMR (300 MHz, CDCl3) δ 2.07 (s, 12H), 2.34
(s, 6H), 4.55 (s, 1H), 6.99 (s, br, 4H), 7.04 (m, 3H); 13C NMR
(75.5 MHz, CDCl3) δ 20.2, 21.1, 120.6, 126.8, 128.4, 129.5,
133.2, 137.1, 137.4, 149.4; HRMS (CI) calcd for C24H27O [M+
+ H] 331.2062, found 331.2054. Anal. Calcd for C24H26O: C,
87.23; H, 7.93. Found: C, 86.99; H, 8.01.
Cou p lin g of 2-Na p h th ol w ith 4-Br om oa n isole (Ta ble
3, en tr y 6). Column chromatography (MeOH/CHCl3, 1:99)
gave 6a a (20 mg, 8%, impure) and 11a a (102 mg, 29%).
3-(4-Meth oxy-p h en yl)-n a p h th a len e-2-ol (6a a ). Light-
sensitive, colorless solid; Rf 0.31 (MeOH/CHCl3, 1:99); 1H NMR
(300 MHz, CDCl3) δ 3.89 (s, 3H), 5.32 (s, 1H), 7.06 (d, J ) 8.9
Hz, 2H), 7.32 (d, J ) 0.6 Hz, 1H), 7.35 (m, 1H), 7.43 (m, 1H),
7.50 (d, J ) 8.9 Hz, 2H), 7.71 (d, J ) 0.6 Hz, 1H), 7.73 (m,
1H), 7.78 (m, 1H); 13C NMR (75.5 MHz, CDCl3) δ 55.4, 110.0,
114.6, 123.8, 126.2, 126.3, 127.6, 128.8, 128.8, 129.3, 130.1,
130.5, 134.1, 150.9, 159.5; HRMS (CI) calcd for C17H15O2 [M+
+ H] 251.1072, found 251.1073.
1,3-Bis(4-m et h oxy-p h en yl)-n a p h t h a len e-2-ol (11a a ).
Light-sensitive, colorless solid; Rf 0.50 (MeOH/CHCl3, 1:99);
1H NMR (300 MHz, CDCl3) δ 3.88 (s, 3H), 3.92 (s, 3H), 5.36
(s, 1H), 7.03 (d, J ) 8.9 Hz, 2H), 7.13 (d, J ) 8.8 Hz, 2H), 7.38
(m, 3H), 7.40 (d, J ) 8.8 Hz, 2H), 7.63 (d, J ) 8.9 Hz, 2H),
7.80 (s, 1H), 7.82 (m, 1H); 13C NMR (75.5 MHz, CDCl3) δ 55.3,
55.3, 113.9, 114.9, 121.3, 123.5, 124.6, 126.1, 126.3, 127.9,
128.8, 129.1, 129.8, 130.2, 130.7, 132.4, 133.0, 148.0, 159.1,
159.5; HRMS (CI) calcd for C24H21O3 [M+ + H] 357.1490, found
Cou p lin g of 3-Met h ylp h en ol w it h 4-Br om oa n isole
(Ta ble 3, en tr y 3). Column chromatography (MeOH/CHCl3,
1:99) gave 6x (32 mg, 15%, impure) and 11x (76 mg, 24%).
J . Org. Chem, Vol. 68, No. 22, 2003 8681

Bedford and Limmert
357.1490. Anal. Calcd for C24H20O3: C, 80.88; H, 5.66. Found:
C, 81.08; H, 5.53.
Cou p lin g of 2-Isop r op ylp h en ol w ith 4-Br om oa n isole
(Ta ble 3, en tr y 10). Compound 6s, 166 mg, (69%). Data as
above.
Cou p lin g of 2-P h en ylp h en ol w it h 4-Br om oa n isole
(Ta ble 3, en t r y 7). 4-Met h oxy-[1,1′;3′,1′′]t er p h en yl-2′-ol
(6a b). Colorless solid, 147 mg (53%); Rf 0.57 (CHCl3); 1H NMR
(300 MHz, CDCl3) δ 3.87 (s, 3H), 5.40 (s, 1H), 7.02 (d, J ) 8.4
Hz, 2H), 7.05 (apparent t (dd), J ) 7.5 Hz, 1H), 7.26 (d, J )
7.5 Hz, 2H), 7.39 (m, 1H), 7.47 (m, 2H), 7.49 (d, J ) 8.4 Hz,
2H), 7.57 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ 55.3, 114.3,
120.6, 127.6, 128.4, 128.6, 128.8, 129.3, 129.6, 129.6, 129.9,
130.5, 137.6, 149.3, 159.1; HRMS (CI) calcd for C19H17O2 [M+
+ H] 1229, found 277.1222. Anal. Calcd for C19H16O2: C, 82.58;
H, 5.84. Found: C, 82.90; H, 5.76.
Cou plin g of 2-Eth ylph en ol with 4-Br om oan isole (Table
3, en tr y 11). Compound 6t, 176 mg (77%). Data as above.
Cou p lin g of 2-Met h ylp h en ol w it h 4-Br om oa n isole
(Ta ble 3, en tr y 12). Column chromatography (MeOH/CHCl3/
hexane, 0.1:1:4);) gave 6u (60 mg, 28%) and 7u (73 mg, 34%,
impure). Data for 6u as above.
3-ter t-Bu t yl-4′,4′′-d im et h oxy-[1,1′;2′,1′′]t er p h en yl-2-ol
(7u ). Colorless oil; Rf 0.07 (MeOH/CHCl3/hexane, 0.1:1:4); 1H
NMR (300 MHz, CDCl3) δ 2.17 (s, 3H), 3.76 (s, 3H), 3.89 (s,
3H), 4.89 (s, 1H), 6.73 (dd, J ) 7.8, 7.2 Hz, 1H), 6.75 (d, J )
8.7 Hz, 2H), 6.84 (dd, J ) 7.8, 1.5 Hz, 1H), 6.97 (dd, J ) 8.4,
2.6 Hz, 1H), 7.01 (m, 1H), 7.03 (d, J ) 2.6 Hz, 1H), 7.10 (d, J
) 8.7 Hz, 2H), 7.38 (d, 1H, J ) 8.4 Hz); 13C NMR (75.5 MHz,
CDCl3) δ 16.2, 55.1, 55.4, 113.2, 113.4, 115.9, 119.8, 124.2,
127.0, 127.2, 128.8, 129.9, 130.1, 132.6, 132.7, 142.6, 150.8,
158.7, 159.6; HRMS (CI) calcd for C21H21O3 [M+ + H] 321.1490,
found 321.1489.
Cou p lin g of 2-Meth oxyp h en ol w ith 4-Br om oa n isole
(Ta b le 3, en t r y 8). 3,4′-Dim et h oxy-b ip h en yl-2-ol (6a c).
1
Colorless solid, 164 mg (71%); Rf 0.30 (CHCl3); H NMR (300
MHz, CDCl3) δ 3.86 (s, 3H), 3.94 (s, 3H), 5.88 (s, 1H), 6.86
(dd, J ) 7.7, 2.0 Hz, 1H), 6.92 (apparent t (dd), J ) 7.7 Hz,
1H), 7.16 (dd, J ) 7.7, 2.0 Hz, 1H), 6.99 (d, J ) 8.6 Hz, 2H),
7.38 (d, J ) 8.6 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 55.1,
55.2, 109.2, 113.6, 119.6, 122.5, 127.3, 130.0, 130.2, 142.6,
146.8, 158.7; HRMS (CI) calcd for C14H15O3 [M+ + H] 231.1021,
found 231.1016. Anal. Calcd for C14H14O3: C, 73.03; H, 6.13.
Found: C, 73.20; H, 6.13.
Cou p lin g of 2-ter t-Bu tylp h en ol w ith 4-Br om oa n isole
(Ta ble 3, en tr y 13). Compound 6d , 75 mg (29%). Data as
above.
Cou p lin g of 1-Na p h th ol w ith 4-Br om oa n isole (Ta ble
3, en tr y 9). Column chromatography (CHCl3) gave 6a d (96
mg, 38%) and 10a d (11 mg, 3%, impure).
Cou p lin g of 2-Isop r op yl P h en ol w ith 2-Br om o-p-xy-
len e (Ta ble 3, en tr y 14). 3-Isop r op yl-2′,5′-d im eth yl-bi-
p h en yl-2-ol (6a e). Colorless oil, 64 mg (27%); Rf 0.44 (CHCl3/
2-(4-Meth oxy-p h en yl)-n a p h th a len e-1-ol (6a d ). Light-
sensitive, colorless solid; Rf 0.55 (CHCl3); 1H NMR (300 MHz,
CDCl3) δ 3.89 (s, 3H), 5.86 (s, 1H), 7.08 (d, 2H, J ) 8.9 Hz),
7.34 (d, 1H, J ) 8.4 Hz), 7.47 (d, 2H, J ) 8.9 Hz), 7.49 (m,
3H), 7.83 (m, 1H), 8.32 (m, 1H); 13C NMR (75.5 MHz, CDCl3)
δ 55.3, 115.0, 120.0, 120.9, 122.3, 124.2, 125.4, 126.2, 127.4,
127.7, 129.3, 130.5, 133.9, 147.7, 159.2; HRMS (CI) calcd for
1
hexane, 1:2); H NMR (300 MHz, CDCl3) δ 1.28 (d, 6H, J )
6.9 Hz), 2.12 (s, 3H), 2.25 (s, 3H), 3.33 (sept., 1H, J ) 6.9 Hz),
4.82 (s, 1H), 6.92 (m, 2H), 7.08 (d, br, 1H, J ) 1,9 Hz), 7.14
(dd, br, 1H, J ) 8.1, 1.9 Hz), 7.22 (dd, 1H, J ) 7.7, 1.8 Hz),
7.28 (d, br, 1H, J ) 8.1 Hz); 13C NMR (75.5 MHz, CDCl3) δ
19.2, 20.9, 22.5, 22.6, 27.2, 120.0, 125.6, 127.2, 127.4, 129.2,
130.6, 131.2, 134.2, 134.6, 135.8, 136.1, 149.6; HRMS (CI) calcd
for C17H21O [M+ + H] 241.1592, found 241.1605. Anal. Calcd
for C17H20O: C, 84.96; H, 8.39. Found: C, 85.47; H, 8.58.
C
C
17H15O2 [M+ + H] 251.1072, found 251.1070. Anal. Calcd for
17H14O2: C, 81.58; H, 5.64. Found: C, 81.58; H, 5.47.
2,8-Bis(4-m et h oxy-p h en yl)-n a p h t h a len e-1-ol (10a d ).
Light-sensitive, pale yellow oil; Rf 0.55 (CHCl3); 1H NMR (300
MHz, CDCl3) δ 3.83 (s, 3H), 3.86 (s, 3H), 5.95 (s, 1H), 6.95 (d,
2H, J ) 8.9 Hz), 7.00 (d, 2H, J ) 8.8 Hz), 7.21 (dd, 1H, J )
7.0, 1.4 Hz), 7.43 (dd, 1H, J ) 8.2, 7.0 Hz), 7.44 (d, 2H, J )
8.8 Hz), 7.45 (d, 1H, J ) 8.4 Hz), 7.48 (d, 2H, J ) 8.9 Hz),
7.54 (d, 1H, J ) 8.4 Hz), 7.84 (dd, 1H, J ) 8.2, 1.4 Hz); 13C
NMR (75.5 MHz, CDCl3) δ 55.3, 55.4, 113.7, 114.1, 120.6,
121.7, 123.6, 124.8, 128.4, 129.0, 129.4, 130.7, 130.8, 131.0,
133.5, 134.9, 136.4, 149.3, 158.5, 158.6; HRMS (CI) calcd for
Ack n ow led gm en t. We thank the EPSRC for fund-
ing (PDRA for M.E.L.).
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal section and 1H and 13C NMR spectra of the coupled
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
C
24H21O3 [M+ + H] 357.1490, found 357.1491.
J O030157K
8682 J . Org. Chem., Vol. 68, No. 22, 2003