Radical dearomatization of arenes and heteroarenes

Article abstract of DOI:10.1016/j.tet.2006.05.051

The stannane-mediated benzeneselenol-catalyzed addition of aryl iodides to a range of arenes and aromatic hetereocycles has been studied. With furan, thiophene, and several carbocyclic arenes, the addition takes place with quenching of the adduct radical by the catalytic selenol leading to moderate yields of aryl-dihydroarenes. With nitrogen heterocycles, on the other hand, it was not possible to suppress aromatization of the adduct radical and fully aromatized products were isolated. Aryl iodides bearing hydrogen bond donating groups in the ortho-position add to nitrogen heterocycles with high selectivity ortho- to the nitrogen, affording a simple one-step synthesis of potential chelating ligands. While 2-iodophenol is an excellent aryl radical source in these reactions, the homologous 1-iodo-2-naphthol fails owing to its reaction with diphenyl diselenide, which gives 1-phenylseleno-2-naphthol in high yield.

Full text of DOI:10.1016/j.tet.2006.05.051

Tetrahedron 62 (2006) 7824–7837
Radical dearomatization of arenes and heteroarenes
*
David Crich and Mitesh Patel
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
Received 24 March 2006; revised 18 May 2006; accepted 22 May 2006
Available online 15 June 2006
Abstract—The stannane-mediated benzeneselenol-catalyzed addition of aryl iodides to a range of arenes and aromatic hetereocycles has
been studied. With furan, thiophene, and several carbocyclic arenes, the addition takes place with quenching of the adduct radical by the cata-
lytic selenol leading to moderate yields of aryl-dihydroarenes. With nitrogen heterocycles, on the other hand, it was not possible to suppress
aromatization of the adduct radical and fully aromatized products were isolated. Aryl iodides bearing hydrogen bond donating groups in the
ortho-position add to nitrogen heterocycles with high selectivity ortho- to the nitrogen, affording a simple one-step synthesis of potential che-
lating ligands. While 2-iodophenol is an excellent aryl radical source in these reactions, the homologous 1-iodo-2-naphthol fails owing to its
reaction with diphenyl diselenide, which gives 1-phenylseleno-2-naphthol in high yield.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
application of copious amounts of initiator.12 Indeed, the
azo-type initiators are now seen to serve the important func-
tion of oxidant for the cyclohexadienyl radical in addition to
their more obvious planned function.13–16
A recurring theme in our laboratory in recent years has been
the reductive radical arylation of benzene leading to the for-
mation of 3-arylcyclohexa-1,4-dienes, and the application of
this reaction in total synthesis. In this chemistry, aryl radicals
add rapidly to arenes to give cyclohexadienyl radicals
substituted with aryl groups at the 6-position, which undergo
hydrogen atom transfer from catalytic benzeneselenol,
yielding the reaction product and a benzeneselenyl radical.1
The benzeneselenyl radical then abstracts hydrogen from
tributyltin hydride,2,3 the stoichiometric reductant, thereby
regenerating the catalytic selenol and the stannyl radical
necessary for formation of the aryl radical from the aryl
iodide. Overall, a four propagation step radical chain
sequence is involved (Scheme 1).1 The catalytic benzene-
selenol is necessary because, under typical preparative
radical chain conditions, the intermediate cyclohexadienyl
radical is insufficiently reactive to propagate the radical
chain by hydrogen atom abstraction from stannane or silane
hydrogen atom donors. Although the Sn–H and Se–H bond
dissociation energies are very similar,4–6 the selenol traps
alkyl radicals some 500 times faster than the stannane,7–9 be-
cause of the operation of a polarity effect.10 The interrupted
propagation in the absence of selenol results in the formation
of rearomatized biaryls and the need for large quantities of rad-
ical initiator.11 Similarly, the intramolecular version of simple
stannane-mediated, cyclizations of aryl radical onto arenes, is
marked by the formation of fully re-oxidized products and the
Bu3SnI
Ar
+
Ar
(1)
(2)
Bu3Sn
Ar
+
Ar-I
+
Ar
Ar
+
PhSe-H
Bu3SnH
+
PhSe
(3)
(4)
PhSe
+
PhSeH
+
Bu3Sn
Scheme 1. Mechanism of dearomatizing aryl radical addition to arenes.
The benzeneselenol-catalyzed chemistry is rendered practi-
cal by the rapid in situ reduction of diphenyl diselenide to
benzeneselenol by the stannane, which enables the direct
handling of the air-sensitive selenol to be avoided
(Scheme 2).3
Bu3SnH + PhSeSePh
Bu3SnSePh + PhSeH
Scheme 2. In situ selenol generation.
In the reductive radical arylation of benzene (Scheme 1)
regiochemistry is not an issue in the addition step, and only
becomes a concern in the hydrogen atom transfer step to
the cyclohexadienyl radical when formation of the skipped
diene is preferred over that of the conjugated diene because
of the higher spin density on the central carbon. However, in
Keywords: Radical; Arylation; Cyclohexadienyl; Dearomatization.
* Corresponding author. Tel.: +1 312 996 5189; fax: +1 312 996 0431;
e-mail: dcrich@uic.edu
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.051

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7825
additions to aromatic heterocycles and other simple arenes
the question of regioselectivity also arises in the initial
addition reaction, resulting in potentially complex reaction
mixtures.17 In spite of this concern, we were motivated to in-
vestigate the use of a broader range of arenes and of aromatic
heterocycles as substrates in this chemistry, and report here
in full on our explorations.18
opposed to the 20 mol % used in our study. It is not clear
at the present time how the selenol/diselenide is achieving
catalysis: one possibility is the quenching of the azacyclo-
hexadienyl radical by diphenyl diselenide to give an aryl
phenylselenyl azacyclohexadiene, which spontaneously
eliminates benzeneselenol to give the final product. Another
possibility is the oxidation of the electron-rich azacyclohexa-
dienyl radical to the corresponding cation by an organosele-
nium species, such as diphenyl diselenide, or tributylstannyl
phenyl selenide.
2. Results and discussion
2.1. Nitrogen heterocycles
With N-methoxycarbonyl-o-iodoaniline 1 as substrate 38%
of the ortho-substitution product 11 was obtained, along
with 3% of the meta-isomer 12 (Table 1, entry 1). Likewise,
o-iodophenol 2, o-iodoaniline 7, and o-iodo-N-methyl-
aniline 8 all afforded predominantly the ortho-products
(Table 1, entries 2, 7, and 8). In contrast, with methyl o-iodo-
benzoate 3, p-bromoiodobenzene 4, 2-iodothiophene 5, and
o-iodoanisole 9 the ortho:para ratio of products was much
lower (Table 1, entries 3, 4, 5, and 9). In most cases, minor
amounts of the para-isomers were also isolated (Table 1).
The improved ratios in favor of the ortho-substituted product
seen with 1, 2, 7, and 8 are attributed to hydrogen bonding of
the substrate to pyridine resulting in both an activating and
a directing effect. The exception, o-iodovanillin 6, is
explained by preferential intramolecular hydrogen bonding
to the methoxy group.
Our attention was first directed at pyridine as substrate in
view of its ready availability, convenient boiling point, and
its well-established free addition radical chemistry, espe-
cially that of pyridinium salts.12,19 The addition of aryl rad-
icals to pyridine and substituted pyridines was studied some
40 years ago using diazonium salts as radical precursors in
the Gomberg–Hey reaction, and it was determined that the
relative rate of addition of the 4-bromophenyl radical to pyr-
idine with respect to benzene was 0.87.20,21 Relative rates of
addition of phenyl radicals, generated by decomposition of
benzoyl peroxide, to alkylpyridines and benzene were also
known and of a comparable magnitude.22–24 The photolysis
of triphenylbismuth had also been employed as a means of
generating phenyl radicals for addition to pyridine.25
All of the early work on aryl radical addition to pyridine
indicated a small preference for attack at the ortho-position,
the extent of which was found to depend on the nature of the
ortho-substituent on the attacking aryl radical, with attack at
the pyridine para-position being the least favored.20,21,25–27
Much more recently, and while this work was in progress,
Alvarez-Builla and co-workers reported on the tris(tri-
methylsilyl)silane-mediated addition of aryl bromides to
pyridine and obtained mixtures of the fully aromatic biaryl
products, in which the isomer arising from attack at
the pyridine 2-position predominated (2-aryl:3-aryl:4-
arylw4:1:1).28
In the nitrogen heterocycles, we also briefly investigated
additions to quinoline, isoquinoline, benzothiazole, and pyr-
role with varying degrees of success (Table 2). In accordance
with the literature for the addition of benzoyl peroxide-gen-
erated phenyl radicals to quinoline, when phenylation at all
positions was found,31,32 a complex reaction mixture was
obtained when o-iodophenol was heated to reflux in benzene
in the presence of 30 equiv of quinoline, catalytic diphenyl
diselenide, and tributyltin hydride. Only one product was
isolated pure from this reaction mixture and that in very
low yield (Table 2, entry 1). With isoquinoline on the other
hand, a much cleaner reaction was observed and one very
predominant product 39, resulting from attack at the 1-posi-
tion, was obtained in 44% yield. The only other product 40
isolated in low yield was that of substitution at the 3-position
(Table 2, entry 2). The formation of the 1-arylisoquinoline as
the major product is in accord with earlier work on the addi-
tion of phenyl radicals, generated either by photolysis of
phenylthallium bis(trifluoroacetate) or by decomposition
of the benzenediazonium cation, to isoquinoline.33 However,
the selectivity is greater than would have been anticipated
on the basis of those earlier studies. Furthermore, the forma-
tion of the 3-arylisoquinoline as the second most abundant
product does not agree with the earlier phenylation studies,
when the 3-position was found to be one of the least reactive.
As with the additions to pyridine, we invoke hydrogen bond-
ing of the heterocycle with the o-iodophenol substrate as the
factor increasing the selectivity for attack at both the 1- and
the 3-positions.
On the basis of this literature precedent, the success of the
selenol-mediated reductive arylations of benzene, and the
common occurrence of dihydropyridines in both nature
and the laboratory,29,30 we were surprised to find that the
reaction of various aryl iodides with tributyltin hydride
and AIBN, catalyzed by diphenyl diselenide yielded, not
the anticipated aryl dihydropyridines, but rather the fully
aromatic aryl pyridines (Table 1). Dihydropyridines were
not formed in these reactions, as determined by inspection
of the crude reaction mixtures by NMR spectroscopy; pre-
sumably, the azacyclohexadienyl radical intermediates are
too stable to propagate the chain by hydrogen atom abstrac-
tion from the selenol. Nevertheless, the diphenyl diselenide/
benzeneselenol had a beneficial effect on these reactions as
significantly lower conversions were obtained in its absence.
For example, heating of 2 with tributyltin hydride and AIBN
in pyridine in the absence of diphenyl diselenide, but under
otherwise standard conditions, gave 13, 14, and 15 in 9, 4,
and 1% yield, respectively, along with 47% of recovered
substrate. The beneficial effect of the selenide is also appar-
ent from comparison with the Alvarez-Builla tris(trimethyl-
silyl)silane-mediated additions to pyridine,28 which were
conducted with greater than stoichiometric AIBN as
A brief investigation of aryl radical addition to pyrrole under
our standard conditions was unsatisfactory, resulting in the
isolation of only one major product, the ortho-substituted
product 41, in low yield (Table 2, entry 3). With 20 equiv
of benzothiazole in benzene the major product 42 was that

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D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
Table 1. Aryl radical additions to pyridine
Entry
Substrate
Products (yield)
I
N
1
NHCOOMe
NHCOOMe
12 (3%)
N
MeOOCHN
1
11 (38%)
I
N
N
N
2
3
OH
HO
OH
14 (16%)
HO
N
2
15 (10%)
13 (36%)
I
N
COOMe
COOMe
MeOOC
N
MeOOC
3
18 (9%)
17 (22%)
16 (20%)
Br
Br
N
Br
I
Br
N
4
5
N
4
21 (5%)
19 (18%)
20 (12%)
S
S
S
N
I
S
N
N
5
24 (7%)
22 (19%)
23 (24%)
CHO
OHC
I
CHO
N
OH
6
OMe
HO
OMe
OH
OMe
N
6
25 (17%)
26 (17%)
I
N
N
N
7
8
NH2
H2N
NH2
28 (4%)
H2N
N
7
29 (4%)
27 (18%)
I
N
NHMe
NHMe
31 (7%)
MeHN
N
MeHN
8
32 (5%)
30 (25%)
I
N
N
9
OMe
MeO
OMe
34 (23%)
MeO
N
9
35 (10%)
33 (20%)
I
N
10
N
OH
HO
N
10
36 (13%)

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
Table 2. Aryl radical addition to other nitrogen heterocycles
7827
Entry
Heterocycle
Substrate
Products (yield)
OH
N
1
Quinoline
I
HO
2
38 (5%)
N
OH
OH
2
3
Isoquinoline
I
N
OH
2
40 (4%)
39 (44%)
OH
OH
N
H
Pyrrole
I
2
41 (17%)
HO
N
OH
OH
N
4
Benzothiazole
I
S
S
2
42 (19%)
43 (7%)
SePh
I
OH
OH
5
Isoquinoline
44 (88%)a
37
a
Based on diphenyl diselenide.
of attack in the heterocyclic ring, with rearomatization.
However, a minor product 43 was also obtained, which re-
sulted from attack on the benzenoid ring at the 4-position,
whose structure was established crystallographically.y The
predominant attack at the benzothiazole 2-position, with
that at the 4-position being the second most important, is
in agreement with the earlier literature on the radical phenyl-
ation of this heterocycle with benzoyl peroxide.34
is the result of consumption of the catalyst in an unantici-
pated reaction with the b-naphthol.
2.2. Oxygen and sulfur heterocycles
With furan and thiophene as aryl radical trap, the chemistry
reverted to the pattern established with benzene, with effi-
cient trapping of the adduct radical, and good chain propaga-
tion in the presence of catalytic benzeneselenol. Aryl radical
addition to furan and thiophene had been previously studied,
with aryl radicals derived from the thermolysis of phenyl-
azotriphenylmethane, and from the metal catalyzed
decomposium of the benzenediazonium ion.37,38 With phe-
nylazotriphenylmethane dearomatized products were ob-
tained, owing to the combination of the initial adduct
radical with the triphenylmethyl radical,37 but the presence
of the triphenylmethyl group obviously detracts from the
synthetic utility of this method.38 As expected, rearomatized
products were obtained with diazonium salt-derived phenyl
radicals. A series of competition reactions revealed the rela-
tive rates of addition of the phenyl radical to furan, thio-
phene, and benzene to be 11.5:2.6:1.37
The clean and successful addition of o-iodophenol to iso-
quinoline prompted an investigation of 1-iodo-2-naphthol
37 in this reaction, with a view to a short synthesis of
1-(2-hydroxy-1-naphthyl)isoquinoline.35 Contrary to our ex-
pectations, a complex reaction mixture was obtained from
which we were unable to isolate the desired product, but
from which we obtained 1-phenylselenyl-2-naphthol36 44
in 88% yield based on diphenyl diselenide (Table 2, entry 5).
Blank reactions in which 44 was formed in high yield from
the reaction of diphenyl diselenide with 37 in benzene at
reflux, in the absence of isoquinoline, stannane and AIBN,
indicate that the failure of the radical reaction in this case
A practical problem faced in the additions to furan was that
of initiation. Use of our standard initiator, AIBN, with its
half life of 2 h at 80 ꢀC, suitable for reactions in benzene,39
y
CCDC 607627 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

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D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
resulted in no observable reaction at the boiling point
(32 ꢀC) of furan. A solution to this problem was found
with 2,20-azobis(4-methoxy-2,4-dimethylvaleronitrile)
(V-70), which is reported to have a half life of 10 h at
30 ꢀC in toluene,40,41 for the commercial ꢁ/meso-isomer.
With this initiator, the benzeneselenol-catalyzed, stannane-
mediated addition of aryl iodides to furan took place
smoothly, giving yields of isolated products (Table 3, entries
1–5) comparable to those for addition to benzene. Likewise,
additions to thiophene (bp 84 ꢀC) proceeded smoothly with
V-70 as initiator when the reactions were carried out at an oil
bath temperature of 50 ꢀC (Table 3, entries 6–9). In the
additions to furan attack of the aryl radical at the 2-position
was very strongly favored, in keeping with the previous
literature observations.37 Similarly, the additions to thio-
phene yielded very predominantly the product of reaction
at the 2-position, with only a minor amount of a product
from attack at the 3-position isolated in one example (Table
3, entry 7). In the case of furan, the intermediate oxyallyl
radical was quenched preferentially at the distal terminus
Table 3. Aryl radical addition to furan and thiophene
Entry
Heterocycle
Substrate
2,3-Dihydro products (yield)
2,5-Dihydro products (yield)
O
OH
OH
O
1
Furan
O
I
2
47 (14%)
46 (45%)
OH
MeO
O
CHO
MeO
OH
I
O
2
Furan
O
OMe
OHC
CHO
48 (51%)
6
49 (14%)
CN
CN
CN
I
O
O
3
4
5
6
7
Furan
45
50 (45%)
51(22%)
CO2Me
I
O
O
Furan
CO2Me
CO2Me
3
52 (32%)
53 (10%)
NHCO2Me
O
O
Furan
I
NHCO2Me
NHCO2Me
54 (43%)
1
55 (19%)
OH
S
OH
S
Thiophene
Thiophene
I
O
2
56 (4%)
57 (32%)
CN
CN
S
+
NC
S
I
CN
S
45
60 (25%)
58 + 59 (13%) 1.4:1
CO2Me
S
S
8
9
Thiophene
Thiophene
I
CO2Me
CO2Me
3
62 (35%)
61 (15%)
NHCO2Me
S
S
I
NHCO2Me
NHCO2Me
1
63 (11%)
64 (31%)

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7829
to the oxygen atom, giving the 2,3-dihydro-2-arylfurans,
with a preference over the 2,5-dihydro-2-aryl isomers vary-
ing between 2:1 and 3.6:1. With thiophene, this preference
was reversed with proximal quenching of the 1-thioallyl rad-
ical being preferred and the 2,5-dihydro-2-arylthiophenes
the major product (Scheme 3). We attribute the differences
in regioselectivity of hydrogen atom abstraction between
the furan and thiophene series to a change in spin delocaliza-
tion in the intermediate heteroatom-substituted allyl radicals
as the heteroatom is changed from oxygen to sulfur. Indeed,
electron spin resonance hyperfine splitting constants indi-
cate that, in the 1-tert-butylthioallyl and 1-tert-butoxyallyl
radicals, the alkylthio group is more effective at localizing
spin than the alkoxy group.42–45 As the recommended C–H
bond strengths in methanol, methylamine, and methanethiol
are very close,46 the likelihood that the change in regioselec-
tivity results from any differences in exothermicity of the
quenching step is considered small.
biphenyl 68 from reaction at the para-position. Similar re-
sults were obtained with o-iodobenzoic acid (Table 4, entry
2), and with o-iodoaniline (Table 4, entry 3) as the source of
aryl radical, except that in the last case only the fully aroma-
tized products were obtained. The cis-fused nature of the
ring junction in 66 is assigned based on a NOESY cross
peak between the bridgehead hydrogen and the pseudoaxial,
homoallylic hydrogen adjacent to the methoxy group. The
assignment of the trans-fused ring junction in 69 follows
from the NOESY cross peaks involving the two homoallylic
hydrogens, one of which correlates with the bridgehead
hydrogen, and the other with the methoxy hydrogens.
The absolute rate constant for the addition of phenyl radicals
to chlorobenzene at 25 ꢀC has been determined to be
1.18ꢂ106 Mꢃ1 sꢃ1, by a laser flash photolytic technique,
and so approximately 2.5 times than the comparable addition
to benzene.49,50 Earlier studies found an approximately 1.5:1
preference for the addition of phenyl radicals to the ortho-
position of chlorobenzene, over addition to the para-position
(o-:m-:p-¼3.1:1:1.5).47,51 Under the benzeneselenol-cata-
lyzed conditions, two major products were formed in the
approximate ratio of 3:1, which was altered in favor of
the major isomer on silica gel chromatography owing to
the more rapid decomposition of the minor isomer (Table
4, entry 4). Presumably, the more stabilized 3-chloro-6-
aryl-1,4-cyclohexadienyl radical arising from attack para-
to the chlorine did not propagate the radical chain with the
selenol, and led to decomposition products. The regiochem-
istry of 75 and 76 is based on the coupling, in the 1H NMR
spectra, of the benzylic hydrogen with a single olefinic
hydrogen in 75, and with two olefinic hydrogens in 76.
R
I
M
furan or
thiophene
Bu3Sn
R
R
X
X
X
PhSeH (proximal quench)
M = O, minor; M = S, major
PhSeH
R
M
(distal quench),
M = O, major;
M = S, minor
X
M
R
R
M
X = OH
O
X
With benzonitrile, previously reported to undergo radical
phenylation some 3.9 times faster than benzene,50 and
with a 6:1:3 selectivity for the ortho-position over the
meta- and para-positions,52 we obtained a mixture of three
adducts containing approximately equal proportions of the
ortho- and para-adducts, with less of the meta-adduct (Table
4, entry 5). Unfortunately, we were unable to suppress rear-
omatization in these reactions and the products were ob-
tained as the fully aromatic biphenyl derivatives.
Scheme 3. Aryl addition to furan and thiophene.
The use of o-iodophenols as substrates in the additions to
furan resulted in the immediate cyclization of the 2,3-di-
hydro-2-aryl adducts to give 2,3,4,5-tetrahydro-2,5-epoxy-
1-benzoxepins as the isolated products (Table 3, entries 1
and 2). Presumably, either the phenol itself, or the benzene-
selenol catalyst, promotes cyclization directly in the reaction
mixture as the initial adducts could not be detected by NMR
spectroscopy of the crude reaction mixtures. The analogous
cyclization also occurred in the thiophene series (Table 3,
entry 6), but much more slowly enabling detection of the
intermediate 2,3-dihydro-2-arylthiophene in the crude reac-
tion mixture.
Finally, we investigated addition to naphthalene, employed
as a solution in benzene. Literature reports on the radical
phenylation of naphthalene suggested a strong preference,
varying between 3:1 and >8:1, for attack at the 1-position
over the 2-position.53,54 Working with o-iodophenol, we
found a ratio of 2.8:1 in favor of the adduct at the 1-position
(Table 4, entry 6). While quenching of the benzocyclohexa-
dienyl radical derived from addition of the aryl at the
1-position was efficient, enabling isolation of the 1-phenyl
dihydronaphthalenes, it was not regioselective and gave an
approximately 1:1 mixture of the two regioisomers.
2.3. Carbocyclic arenes
In classical work on the oxidative addition of aryl radicals to
arenes it was established that phenyl radicals, obtained on
decomposition of N-nitrosoacetanilides, add to anisole
with a slight preference for the ortho-position, over the
para- and meta-positions (3.5:1.5:0.9), and that addition to
the ortho-position was some three and a half times more
rapid than the corresponding addition to benzene.17,47,48
Under our conditions, with the radical derived from o-iodo-
phenol, the main isolated product (Table 4, entry 1) was the
methoxytetrahydrodibenzofuran 66, arising from initial
attack at the ortho-position. The biphenyl 67 from ortho-
attack was also obtained, as was a minor amount of the
Interestingly, when the methoxytetrahydrodibenzofuran 66
was allowed to react with allyltrimethylsilane in the pres-
ence of titanium tetrachloride at ꢃ78 ꢀC in dichloromethane
the tertiary ether 83 was formed in high yield (Scheme 4).
This product, whose stereochemical assignment is based
on the NOESY cross peaks of the two homoallylic hydro-
gens with the benzylic hydrogen and the methoxy
hydrogens, arises from Lewis acid-induced cleavage of the

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D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
Table 4. Aryl radical additions to carbocyclic arenes
Entry
Arene
Substrate
Products (yield)
OMe
OMe
H
OH
I
OMe
OMe
1
Anisole
O
OH
OH
68 (5%)
2
66 (20%)
67 (12%)
H
CO2H
I
OMe
OMe
O
2
Anisole
CO2H
CO2H
O
65
70 (7%)
69 (19%)
71 (2%)
MeO
OMe
I
OMe
3
4
5
Anisole
NH2
NH2
NH2
NH2
7
73 (4%)
74(5%)
72 (21%)
Cl
OH
I
Cl
Chlorobenzene
Benzonitrile
OH
OH
2
76 (3%)a
75 (17%)a
CN
OH
I
CN
CN
OH
OH
OH
2
77(10%)
79 (5%)
78 (9%)
HO
HO
OH
I
6
Naphthalene
OH
+
2
80
81
82
(40%) 80:81:82 = 1.4:1.4:1
a
In the crude reaction mixture, the ratio of 75:76 was 3:1. The higher ratio of isolated products is a function of the more rapid decomposition of 76 in the course
of the isolation.
endocyclic acetal bond followed by nucleophilic attack on
the more open face of the subsequent oxacarbenium ion.
isolate arylated dihydroarenes and heteroarenes is strongly
system dependent, with nitrogen heterocycles giving only
fully aromatic products, but furan and thiophene giving pre-
dominantly 2-aryl dihydro systems. Aryl iodides bearing
hydrogen bond donating groups in the ortho-position add
to nitrogen heterocycles with good selectivity ortho- to
nitrogen, thereby providing a facile synthesis of potential
chelating ligands.
OH
H
SiMe3
TiCl4, CH2Cl2,
-78 °C, 84%
O
MeO
83
OMe
66
Scheme 4. Reaction of 66 with allyltrimethylsilane and TiCl4.
4. Experimental
4.1. General
3. Conclusion
All solvents were dried and distilled by standard procedures.
1H NMR and 13C NMR spectra were recorded at 500 MHz
and 125 MHz, respectively, in CDCl3 with chemical shifts
(d) downfield from tetramethylsilane.
Benzeneselenol catalyzes the addition of aryl radicals, de-
rived from aryl iodides by the action of tributyltin hydride,
to a wide range of arenes and hetereoarenes. The ability to

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7831
4.2. General protocol for aryl radical addition to
nitrogen heterocycles
7.44–7.48 (m, 2H), 7.55 (dd, J¼5.0, 1.0 Hz, 2H), 7.74 (dt,
J¼8.0, 2.0 Hz, 1H), 7.81 (d, J¼7.5 Hz, 1H), 8.63 (qd,
J¼4.0, 1.0 Hz, 1H).
A solution of aryl iodide (1 mmol), diphenyl diselenide
(62 mg, 0.2 mmol), and solvent (20 mL) was sparged with
argon for 45 min, followed by heating at 95 ꢀC with stirring.
A solution of AIBN (33 mg, 0.2 mmol) and Bu3SnH
(0.47 mL, 1.75 mmol) in degassed solvent (10 mL) was
added via syringe pump over 16 h, after which heating was
continued for 1 h, before the reaction mixture was cooled
to room temperature and concentrated. The residue was
taken up in 20% EtOAc in hexane (50 mL) and extracted
with 2 N HCl (50 mL), (except Table 2, entries 4 and 5,
which were purified without acidic workup). The aqueous
phase was neutralized with 3 M NaOH and extracted
(EtOAc). The extracts were washed with brine, dried
(Na2SO4), concentrated, and purified by silica gel chromato-
graphy (eluent: EtOAc/hexane).
4.2.7. Methyl 2-(3-pyridyl)benzoate (17). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;59 1H NMR d: 3.66 (s, 3H), 7.32 (dd,
J¼7.5, 0.5 Hz, 1H), 7.37 (br m, 1H), 7.46 (dt, J¼7.5,
0.5 Hz, 1H), 7.56 (dt, J¼7.5, 1.0 Hz, 1H), 7.63 (d,
J¼8.0 Hz, 1H), 7.93 (dd, J¼8.0, 1.5 Hz, 1H), 8.71 (br s, 2H).
4.2.8. Methyl 2-(4-pyridyl)benzoate (18). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;57 1H NMR d: 3.67 (s, 3H), 7.23 (dd, J¼
4.5, 1.5 Hz, 2H), 7.32 (td, J¼8.0, 0.5 Hz, 1H), 7.49 (dt,
J¼7.5, 1.5 Hz, 1H), 7.58 (dt, J¼8.0, 1.5 Hz, 1H), 7.93 (dd,
J¼7.5, 1.5 Hz, 1H), 8.63 (dd, J¼6.0 Hz, 2H).
4.2.9. 2-(4-Bromophenyl)pyridine (19). Reaction solvent:
pyridine; colorless oil; spectroscopic data identical to litera-
ture values;60 1H NMR d: 7.24 (m, 1H), 7.60 (d, J¼8.5 Hz,
2H), 7.69 (d, J¼7.5 Hz, 1H), 7.74 (dt, J¼7.5, 1.0 Hz, 1H),
7.86 (d, J¼6.5 Hz, 2H), 8.68 (td, J¼4.5, 1.0 Hz, 1H).
4.2.1. 2-(2-Pyridyl)methoxycarbamoylbenzene (11). Re-
action solvent: pyridine; white solid; mp 32–34 ꢀC; 1H
NMR d: 3.76 (s, 3H), 7.12 (dt, J¼7.0, 1.0 Hz, 1H), 7.26
(ddd, J¼7.5, 4.5, 1.0 Hz, 1H), 7.40 (dt, J¼8.0, 1.5 Hz,
1H), 7.63 (dd, J¼7.5, 1.5 Hz, 1H), 7.71 (d, J¼8.0 Hz, 1H),
7.81 (dt, J¼8.0, 2.0 Hz, 1H), 8.33 (br d, J¼8.5 Hz, 1H),
8.65 (br d, J¼6.0 Hz, 1H), 11.52 (br s, 1H); 13C NMR d:
52.0, 120.4, 121.8, 122.6, 122.9, 125.3, 128.9, 130.1,
137.6, 137.8, 147.6, 154.5, 158.2; Anal. Calcd for
C13H12N2O2: C, 68.41; H, 5.30. Found: C, 68.37; H, 5.19.
4.2.10. 3-(4-Bromophenyl)pyridine (20). Reaction solvent:
pyridine; colorless oil; spectroscopic data identical to litera-
ture values;21 1H NMR d: 7.36 (m, 1H), 7.44 (d, J¼8.5 Hz,
2H), 7.60 (d, J¼8.5 Hz, 2H), 7.83 (td, J¼8.0, 1.5 Hz, 1H),
8.60 (d, J¼3.5 Hz, 1H), 8.80 (s, 1H).
4.2.2. 2-(3-Pyridyl)methoxycarbamoylbenzene (12). Re-
4.2.11. 4-(4-Bromophenyl)pyridine (21). Reaction solvent:
pyridine; white solid; mp 129.5 ꢀC, lit.61 130 ꢀC; spectro-
scopic data identical to literature values;61 1H NMR d:
7.47 (dd, J¼4.5, 1.5 Hz, 2H), 7.51 (d, J¼7.0 Hz, 2H), 7.61
(d, J¼7.0 Hz, 2H), 8.67 (dd, J¼4.5, 1.5 Hz, 2H).
1
action solvent: pyridine; white solid; mp 108–110 ꢀC; H
NMR d: 3.71 (s, 3H), 6.52 (br s, 1H), 7.20 (m, 2H), 7.41
(m, 2H), 7.70 (d, J¼7.5 Hz, 1H), 8.05 (br s, 1H), 8.63 (m,
2H); 13C NMR d: 52.4, 120.9, 123.8, 124.1, 129.4, 130.3,
134.1, 135.0, 136.9, 149.0, 150.0, 154.0; Anal. Calcd for
C13H12N2O2: C, 68.41; H, 5.30. Found: C, 68.24; H, 5.20.
4.2.12. 2-(2-Thienyl)pyridine (22). Reaction solvent: pyri-
dine; white solid; mp 61.5 ꢀC, lit.62 61–62 ꢀC; spectroscopic
data identical to literature values;62 1H NMR d: 7.13 (m, 2H),
7.39 (dd, J¼5.0, 1.0 Hz, 1H), 7.58 (dd, J¼4.0, 1.0 Hz, 1H),
7.66 (m, 2H), 8.56 (d, J¼4.5 Hz, 1H).
4.2.3. 2-(2-Hydroxyphenyl)pyridine (13). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;55 1H NMR d: 6.92 (dt, J¼8.0, 1.0 Hz,
1H), 7.06 (dd, J¼8.0, 1.0 Hz, 1H), 7.19–7.22 (m, 1H),
7.32 (dt, J¼7.0, 1.5 Hz, 1H), 7.77–7.80 (m, 2H), 7.88 (d,
J¼8.5 Hz, 1H), 8.48 (d, J¼4.5 Hz, 1H).
4.2.13. 3-(2-Thienyl)pyridine (23). Reaction solvent: pyri-
dine; colorless oil; spectroscopic data identical to literature
values;63 1H NMR d: 7.12 (dd, J¼5.0, 4.0 Hz, 1H), 7.30
(m, 1H), 7.35 (d, J¼4.0 Hz, 2H), 7.86 (td, J¼8.0, 1.5 Hz,
1H), 8.52 (br s, 1H), 8.89 (br s, 1H).
4.2.4. 3-(2-Hydroxyphenyl)pyridine (14). Reaction sol-
vent: pyridine; white solid; mp 162–163 ꢀC, lit.56 171–
1
172 ꢀC; H NMR d: 4.93 (br s, 1H), 6.91–6.94 (m, 2H),
7.21 (dt, J¼9.0, 1.5 Hz, 1H), 7.28 (dd, J¼7.5, 1.5 Hz, 1H),
7.43–7.45 (m, 1H), 8.03 (td, J¼7.5, 2.5 Hz, 1H), 8.41 (dd,
J¼4.5, 1.5 Hz, 1H), 8.73 (dd, J¼2.0, 0.5 Hz, 1H).
4.2.14. 4-(2-Thienyl)pyridine (24). Reaction solvent: pyri-
dine; colorless oil; spectroscopic data identical to literature
values;64 1H NMR d: 7.14 (dd, J¼5.0, 4.0 Hz, 1H), 7.42
(d, J¼5.0 Hz, 1H), 7.51 (m, 3H), 8.61 (br s, 2H).
4.2.5. 4-(2-Hydroxyphenyl)pyridine (15). Reaction sol-
vent: pyridine; white solid; mp 208–210 ꢀC, lit.57 213–
215 ꢀC; spectroscopic data identical to literature values;57
1H NMR d: 4.91 (br s, 1H), 6.92 (m, 2H), 7.24 (dt, J¼7.5,
1.0 Hz, 1H), 7.37 (dd, J¼7.5, 1.5 Hz, 1H), 7.69 (dd,
J¼5.5, 1.5 Hz, 2H), 8.50 (dd, J¼5.0, 1.5 Hz, 2H).
4.2.15. 5-(2-Pyridyl)vanillin (25). Reaction solvent: pyri-
1
dine; yellowish solid; mp 160–161 ꢀC; H NMR d: 3.96
(s, 3H), 7.32 (ddd, J¼7.5, 5.0, 1.0 Hz, 1H), 7.39 (d,
J¼1.5 Hz, 1H), 7.90 (dt, J¼7.5, 1.5 Hz, 1H), 7.94 (d,
J¼2.0 Hz, 1H), 8.0 (d, J¼8.5 Hz, 1H), 8.52 (ddd, J¼5.3,
2.0, 0.5 Hz, 1H), 9.85 (s, 1H); 13C NMR d: 56.2, 110.2,
117.9, 119.4, 122.4, 123.7, 127.4, 138.4, 145.4, 150.3,
156.6, 156.8, 190.6; Anal. Calcd for C13H11NO3: C, 68.11;
H, 4.84. Found: C, 67.83; H, 4.70.
4.2.6. Methyl 2-(2-pyridyl)benzoate (16). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;58 1H NMR d: 3.67 (s, 3H), 7.24 (m, 1H),

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D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
4.2.16. 5-(3-Pyridyl)vanillin (26). Reaction solvent: pyri-
dine; yellowish solid; mp 162–163 ꢀC; 1H NMR d: 3.99 (s,
3H), 7.39 (dd, J¼8.3, 5.0 Hz, 1H), 7.44 (d, J¼2.0 Hz, 1H),
7.50 (d, J¼2.0 Hz, 1H), 7.98 (td, J¼8.0, 2.0 Hz, 1H), 8.58
(dd, J¼5.0, 1.5 Hz, 1H), 8.87 (d, J¼2.5 Hz, 1H), 9.87 (s,
1H); 13C NMR d: 56.5, 108.3, 123.3, 124.1, 128.0, 129.4,
132.5, 136.7, 147.7, 148.4, 149.2, 149.6, 190.7; ESIHRMS,
calcd for C13H11NO3: 230.0817 (M+H+), found: 230.0815.
J¼8.5 Hz, 1H), 7.08 (t, J¼7.0 Hz, 1H), 7.20 (m, 1H), 7.37
(dt, J¼8.5, 2.0 Hz, 1H), 7.69 (dt, J¼7.5, 2.0 Hz, 1H), 7.75
(dd, J¼7.5, 2.0 Hz, 1H), 7.81 (d, J¼8.0 Hz, 1H), 8.70 (d,
J¼4.5 Hz, 1H).
4.2.24. 3-(2-Methoxyphenyl)pyridine (34). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;66 1H NMR d: 3.82 (s, 3H), 6.99 (d,
J¼8.5 Hz, 1H), 7.06 (dt, J¼7.5, 1.0 Hz, 1H), 7.30–7.39
(m, 3H), 7.86 (tt, J¼8.5, 2.5 Hz, 1H), 8.55 (dd, J¼5.0,
2.0 Hz, 1H), 8.77 (dd, J¼2.5, 1.0 Hz, 1H).
4.2.17. 2-(2-Aminophenyl)pyridine (27). Reaction solvent:
pyridine; yellowish oil; spectroscopic data identical to liter-
ature values;65 1H NMR d: 5.48 (br s, 2H), 6.78 (m, 2H), 7.18
(m, 2H), 7.51 (dd, J¼7.5, 1.0 Hz, 1H), 7.56 (d, J¼8.0 Hz,
1H), 7.76 (dt, J¼8.0, 2.0 Hz, 1H), 8.61 (td, J¼5.0, 0.5 Hz,
1H).
4.2.25. 4-(2-Methoxyphenyl)pyridine (35). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;57 1H NMR d: 3.83 (s, 3H), 7.00 (dd,
J¼8.5, 1.0 Hz, 1H), 7.06 (dt, J¼7.0, 0.5 Hz, 1H), 7.34
(dd, J¼7.5, 1.5 Hz, 1H), 7.40 (dt, J¼8.0, 1.5 Hz, 1H), 7.47
(dd, J¼4.5, 2.0 Hz, 2H), 8.62 (dd, J¼4.5, 1.5 Hz, 2H).
4.2.18. 3-(2-Aminophenyl)pyridine (28). Reaction solvent:
pyridine; yellowish oil; spectroscopic data identical to liter-
ature values;66 1H NMR d: 3.51 (br s, 2H), 6.78 (d,
J¼8.0 Hz, 1H), 6.86 (dt, J¼7.5, 0.5 Hz, 1H), 7.10 (dd,
J¼7.5, 2.0 Hz, 1H), 7.21 (dt, J¼7.0, 1.0 Hz, 1H), 7.38 (m,
1H), 7.82 (td, J¼8.0, 1.5 Hz, 1H), 8.60 (dd, J¼4.5, 1.0 Hz,
1H), 8.71 (d, J¼2.5 Hz, 1H).
4.2.26. 6-(2-Pyridyl)-2-picolin-5-ol (36). Reaction solvent:
pyridine; yellowish solid; mp 47–48 ꢀC; 1H NMR d: 2.53 (s,
3H), 7.08 (d, J¼9.0 Hz, 1H), 7.23 (d, J¼9.0 Hz, 1H), 7.31
(ddd, J¼11.5, 5.0, 1.5 Hz, 1H), 7.89 (dt, J¼7.5, 2.0 Hz,
1H), 8.50 (dd, J¼5.0, 1.0 Hz, 1H), 8.63 (d, J¼8.0 Hz, 1H),
14.01 (br s, 1H); 13C NMR d: 23.7, 120.8, 122.8, 125.6,
126.2, 135.3, 137.8, 145.4, 148.1, 154.4, 158.3; Anal. Calcd
for C11H10N2O: C, 70.95; H, 5.41. Found: C, 70.89; H, 5.39.
4.2.19. 4-(2-Aminophenyl)pyridine (29). Reaction solvent:
pyridine; yellowish oil; spectroscopic data identical to liter-
ature values;57 1H NMR d: 3.73 (br s, 2H), 6.77 (d,
J¼8.0 Hz, 1H), 6.85 (dt, J¼8.5, 1.0 Hz, 1H), 7.13 (dd, J¼
7.5, 1.5 Hz, 1H), 7.21 (tt, J¼8.0, 1.0 Hz, 1H), 7.43 (dd,
J¼5.5, 2.0 Hz, 2H), 8.67 (dd, J¼5.5, 1.5 Hz, 2H).
4.2.27. 2-(2-Hydroxyphenyl)quinoline (38). Reaction sol-
vent: benzene (30 equiv of quinoline in benzene); white
solid; mp 110–112 ꢀC, lit.68 109.8–110.7 ꢀC; spectroscopic
data identical to literature values;68 1H NMR d: 6.96 (tt,
J¼8.0, 1.5 Hz, 1H), 7.11 (d, J¼7.5 Hz, 1H), 7.26 (d, J¼
1.5 Hz, 1H), 7.37 (dt, J¼8.5, 1.0 Hz, 1H), 7.54 (dt, J¼7.0,
1.5 Hz, 1H), 7.74 (dt, J¼8.0, 1.0 Hz, 1H), 7.80 (d,
J¼8.0 Hz, 1H), 7.94 (d, J¼7.5 Hz, 1H), 8.02 (dd, J¼8.0,
2.0 Hz, 1H), 8.24 (d, J¼8.5 Hz, 1H), 15.27 (br s, 1H).
4.2.20. 2-[2-(N-Methylamino)phenyl]pyridine (30). Reac-
tion solvent: pyridine; yellowish oil; H NMR d: 2.93 (s,
1
3H), 6.75 (m, 2H), 7.17 (m, 1H), 7.32 (m, 1H), 7.56 (d,
J¼7.5 Hz, 1H), 7.67 (dd, J¼8.0, 1.0 Hz, 1H), 7.75 (m,
1H), 8.02 (br s, 1H), 8.60 (dd, J¼5.0, 1.0 Hz, 1H); 13C
NMR d: 30.0, 110.8, 115.6, 120.8, 121.4, 122.4, 129.4,
130.4, 136.9, 147.5, 148.6, 159.8; ESIHRMS, calcd for
C12H12N2: 185.1079 (M+H+), found: 185.1075.
4.2.28. 1-(2-Hydroxyphenyl)isoquinoline (39). Reaction
solvent: benzene (30 equiv of isoquinoline in benzene);
white solid; mp 160–162 ꢀC, lit.69 166–168 ꢀC; spectro-
scopic data identical to literature values;69 1H NMR d: 7.02
(dt, J¼7.5, 1.0 Hz, 1H), 7.20 (dd, J¼8.5, 1.0 Hz, 1H), 7.39
(dt, J¼8.5, 1.5 Hz, 1H), 7.59–7.63 (m, 2H), 7.71–7.75 (m,
2H), 7.88 (d, J¼8.0 Hz, 1H), 8.45 (m, 2H), 11.82 (br s, 1H).
4.2.21. 3-[2-(N-Methylamino)phenyl]pyridine (31). Reac-
tion solvent: pyridine; white solid; mp 71–73 ꢀC; 1H NMR d:
2.80 (s, 3H), 3.80 (br s, 1H), 6.72 (d, J¼8.5 Hz, 1H), 6.80 (dt,
J¼7.5, 1.0 Hz, 1H), 7.07 (dd, J¼7.5, 2.0 Hz, 1H), 7.31 (dt,
J¼8.5, 2.0 Hz, 1H), 7.37 (dd, J¼4.5, 1.0 Hz, 1H), 7.76
(td, J¼7.5, 2.0 Hz, 1H), 8.59 (dd, J¼5.0, 2.0 Hz, 1H), 8.67
(d, J¼2.0 Hz, 1H); 13C NMR d: 30.7, 110.1, 117.1, 123.6,
129.6, 130.3, 135.2, 137.0, 146.3, 148.5, 150.4; ESIHRMS,
calcd for C12H12N2: 185.1079 (M+H+), found: 185.1084.
4.2.29. 3-(2-Hydroxyphenyl)isoquinoline (40). Reaction
solvent: benzene (30 equiv of isoquinoline in benzene);
1
white solid; mp 112–113 ꢀC; H NMR d: 6.96 (dt, J¼7.0,
1.0 Hz, 1H), 7.06 (d, J¼7.0 Hz, 1H), 7.32 (tt, J¼7.0,
1.5 Hz, 1H), 7.60 (dt, J¼8.0, 1.0 Hz, 1H), 7.74 (dt, J¼
7.0, 1.5 Hz, 1H), 7.89 (d, J¼8.0 Hz, 1H), 7.92 (d,
J¼6.0 Hz, 1H), 8.00 (d, J¼8.0 Hz, 1H), 8.22 (s, 1H), 9.19
(s, 1H), 14.05 (br s, 1H); 13C NMR d: 115.4, 118.7, 119.1,
119.5, 126.2, 126.9, 127.1, 127.4, 127.9, 130.9, 131.4,
137.0, 149.0, 151.2, 159.3; Anal. Calcd for C15H11NO: C,
81.43; H, 5.01. Found: C, 81.39; H, 5.00.
4.2.22. 4-[2-(N-Methylamino)phenyl]pyridine (32). Reac-
tion solvent: pyridine; white solid; mp 133–135 ꢀC; 1H
NMR d: 2.82 (s, 3H), 3.93 (br s, 1H), 6.71 (d, J¼8.0 Hz,
1H), 6.80 (dt, J¼7.5, 1.0 Hz, 1H), 7.09 (dd, J¼7.5, 2.0 Hz,
1H), 7.32 (dt, J¼7.5, 1.5 Hz, 1H), 7.39 (dd, J¼6.0, 2.0 Hz,
2H), 8.66 (dd, J¼6.0, 2.0 Hz, 2H); 13C NMR d: 30.7,
110.3, 117.1, 124.2, 124.4, 129.8, 130.0, 145.8, 147.7,
150.3; ESIHRMS, calcd for C12H12N2: 185.1079 (M+H+),
found: 185.1075.
4.2.30. 2-(2-Hydroxyphenyl)-1H-pyrrole (41). Reaction
solvent: pyrrole; yellowish oil; spectroscopic data identical
to literature values;70 1H NMR d: 5.52 (s, 1H), 6.33 (d,
J¼3.0 Hz, 1H), 6.58 (s, 1H), 6.85 (d, J¼8.0 Hz, 1H), 6.89
(s, 1H), 6.97 (t, J¼7.0 Hz, 1H), 7.09 (t, J¼7.5 Hz, 1H),
4.2.23. 2-(2-Methoxyphenyl)pyridine (33). Reaction sol-
vent: pyridine; colorless oil; spectroscopic data identical to
literature values;67 1H NMR d: 3.84 (s, 3H), 7.00 (d,

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7833
7.55 (d, J¼8.0 Hz, 1H), 9.42 (br s, 1H); 13C NMR d: 106.2,
119.9, 124.8, 126.5, 126.6, 128.8, 129.0, 155.2; ESIHRMS,
calcd for C10H10O2: 185.0579 (M+Na), found: 185.0570.
109.2, 116.3, 118.6, 119.6, 121.5, 127.0, 127.2, 128.8, 151.0.
4.2.31. 2-(2-Hydroxyphenyl)benzothiazole (42). Reaction
solvent: benzene (20 equiv of benzothiazole in benzene);
4.4.3. 9-Methoxy-2,3,4,5-tetrahydro-2,5-epoxy-1-benz-
oxepin-7-carbaldehyde (48). White solid; mp 100–102 ꢀC
(EtOAc/hexane); H NMR d: 2.25–2.35 (m, 4H), 3.90 (s,
1
1
white solid; mp 130–131 ꢀC, lit.71 130–132 ꢀC; H NMR
d: 6.96 (tt, J¼7.5, 1.0 Hz, 1H), 7.12 (dd, J¼8.5, 1.0 Hz,
1H), 7.37–7.42 (m, 2H), 7.50 (dt, J¼8.5, 1.5 Hz, 1H), 7.69
(dd, J¼8.5 Hz, 1.5 Hz, 1H), 7.89 (d, J¼8.5 Hz, 1H), 7.99
(dd, J¼8.0, 1.0 Hz, 1H), 12.53 (s, 1H).
3H), 5.20 (d, J¼5.5 Hz, 1H), 6.09 (d, J¼4.0 Hz, 1H), 7.14
(d, J¼1.0 Hz, 1H), 7.30 (d, J¼1.5 Hz, 1H), 9.79 (s, 1H);
13C NMR d: 34.0, 35.3, 56.1, 77.0, 101.5, 109.7, 121.1,
127.8, 129.1, 145.2, 148.5, 190.6; Anal. Calcd for
C12H12O4: C, 65.45; H, 5.49. Found: C, 65.36; H, 5.57.
4.2.32. 4-(2-Hydroxyphenyl)-4,7-dihydrobenzothiazole
(43). Reaction solvent: benzene (20 equiv of benzothiazole
in benzene); white solid; mp 210–212 ꢀC; 1H NMR d:
3.57–3.59 (m, 2H), 5.12–5.15 (m, 1H), 6.07–6.11 (m, 1H),
6.22–6.26 (m, 1H), 6.89 (dt, J¼7.5, 1.5 Hz, 1H), 7.05 (dd,
J¼8.0, 1.5 Hz, 1H), 7.15–7.19 (m, 2H), 8.67 (s, 1H), 10.10
(br s, 1H); 13C NMR d: 25.4, 37.8, 119.3, 120.7, 124.6,
125.5, 126.9, 127.4, 128.4, 130.3, 150.7, 151.2, 155.5;
EIHRMS, calcd for C13H11NOS: 229.0561 (M+), found:
229.0557.
4.4.4. 3-(2,5-Dihydrofuran-2-yl)-4-hydroxy-5-methoxy-
benzaldehyde (49). Colorless oil; 1H NMR d: 3.95 (s,
3H), 4.83 (dd, J¼12.0, 3.5 Hz, 1H), 4.92 (dd, J¼14.0,
6.5 Hz, 1H), 6.03 (s, 2H), 6.16 (q, J¼4.5 Hz, 1H), 6.70 (s,
1H), 7.35 (d, J¼2.0 Hz, 1H), 7.47 (d, J¼1.5 Hz, 1H), 9.82
(s, 1H); 13C NMR d: 56.3, 75.8, 82.6, 107.7, 124.7, 126.7,
128.0, 128.4, 129.3, 147.1, 148.4, 191.1; ESIHRMS, calcd
for C12H12O4: 243.0634 (M+Na), found: 243.0627.
4.4.5. 2-(2,3-Dihydrofuran-2-yl)benzonitrile (50). Color-
less oil; H NMR d: 2.53 (m, 1H), 3.30 (m, 1H), 4.99 (q,
1
4.3. Reaction of diphenyl diselenide with 1-iodo-2-
naphthol (44)
J¼2.0 Hz, 1H), 5.83 (dd, J¼11.0, 7.5 Hz, 1H), 6.48 (q,
J¼2.5 Hz, 1H), 7.38 (dt, J¼7.0, 2.0 Hz, 1H), 7.59 (m, 2H),
7.65 (dd, J¼7.5, 1.0 Hz, 1H); 13C NMR d: 37.8, 79.8,
99.2, 109.6, 117.3, 125.8, 127.9, 132.9, 133.1, 145.2,
147.3; ESIHRMS, calcd for C11H9NO: 194.0582 (M+Na),
found: 194.0590.
A solution of 1-iodo-2-naphthol (1.0 mmol) and diphenyl
diselenide (62.0 mg, 0.2 mmol) in degassed benzene was
heated to reflux for 4 h. The solvent was evaporated off
under reduced pressure. Purification by silica gel column
chromatography (EtOAc/hexane) afforded compound 44 in
quantitative yield. White solid; mp 79 ꢀC, lit.36 77–78 ꢀC;
1H NMR d: 7.14–7.17 (m, 6H), 7.37–7.40 (m, 2H), 7.51
(dt, J¼7.0 Hz, 1.0 Hz, 1H), 7.82 (d, J¼8.0 Hz, 1H), 7.90
(d, J¼9.0 Hz, 1H), 8.29 (d, J¼8.5 Hz, 1H).
4.4.6. 2-(2,5-Dihydrofuran-2-yl)benzonitrile (51). Color-
less oil; H NMR d: 4.84 (m, 1H), 4.98 (m, 1H), 5.92 (m,
1
1H), 6.10 (m, 2H), 7.37 (dt, J¼7.5, 1.5 Hz, 1H), 7.50 (dd,
J¼8.0, 1.0 Hz, 1H), 7.58 (dt, J¼7.5, 1.5 Hz, 1H), 7.66 (dd,
J¼7.5, 1.0 Hz, 1H); 13C NMR d: 76.5, 86.1, 110.1, 117.4,
127.1, 127.8, 128.1, 133.0, 133.3, 146.2; ESIHRMS, calcd
for C11H9NO: 194.0582 (M+Na), found: 194.0577.
4.4. General protocol for aryl radical addition to oxygen
and sulfur heterocycles
A solution of aryl iodide (1.0 mmol), diphenyl diselenide
(62.0 mg, 0.2 mmol), and freshly distilled furan (thiophene)
(20 mL) was sparged with argon for 45 min, followed by
heating at 50 ꢀC (bath temperature) with stirring. A solution
of 2,20-azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70)
(62.0 mg, 0.2 mmol) and Bu3SnH (0.47 mL, 1.75 mmol) in
degassed furan (thiophene) (10 mL) was added via syringe
pump over 16 h, after which heating was continued for 1 h,
before the reaction mixture was cooled to room temperature
and concentrated under vacuum. The residue was taken up in
acetonitrile (75 mL) and washed with hexane (4ꢂ25 mL).
The acetonitrile phase was concentrated and purified by sil-
ica gel column chromatography (eluent: EtOAc/hexane).
4.4.7. Methyl 2-(2,3-dihydrofuran-2-yl)benzoate (52).
Colorless oil; eluent: 1:1 (hexane/benzene with 0.5%
1
EtOAc); H NMR d: 2.34–2.40 (ddt, J¼15.5, 10.5, 2.0 Hz,
1H), 3.31–3.37 (ddt, J¼15.5, 10.5, 2.5 Hz, 1H), 3.90 (s,
3H), 4.90 (app. q, J¼2.5 Hz, 1H), 6.26 (dd, J¼11.5,
7.5 Hz, 1H), 6.51 (q, J¼3.0 Hz, 1H), 7.33 (dt, J¼8.0,
1.5 Hz, 1H), 7.54 (dt, J¼7.5, 1.0 Hz, 1H), 7.63 (dd, J¼7.5,
1.0 Hz, 1H), 7.98 (dd, J¼7.5, 1.0 Hz, 1H); 13C NMR d:
38.6, 52.1, 79.7, 99.0, 125.5, 126.8, 126.9, 130.7, 132.7,
145.1, 145.8, 167.2; ESIHRMS, calcd for C12H12O3:
227.0684 (M+Na), found: 227.0691.
4.4.8. Methyl 2-(2,5-dihydrofuran-2-yl)benzoate (53).
Colorless oil; eluent: 1:1 (hexane/benzene with 1.5%
EtOAc); H NMR d: 3.90 (s, 3H), 4.85 (m, 1H), 4.95 (m,
4.4.1. 2,3,4,5-Tetrahydro-2,5-epoxy-1-benzoxepin (46).72
Colorless oil; 1H NMR d: 2.19–2.28 (m, 4H), 5.12 (d,
J¼4.5 Hz, 1H), 5.94 (m, 1H), 6.75 (d, J¼8.5 Hz, 1H), 6.84
(dt, J¼7.5, 1.5 Hz, 1H), 6.94 (dd, J¼7.0, 2.0 Hz, 1H), 7.15
(dt, J¼7.5, 2.0 Hz, 1H); 13C NMR d: 33.4, 35.7, 77.2,
100.4, 116.1, 120.1, 124.4, 127.2, 128.7, 150.0.
1
1H), 5.92 (m, 1H), 6.04 (m, 1H), 6.50 (m, 1H), 7.31 (dt,
J¼7.5, 1.0 Hz, 1H), 7.53 (dt, J¼7.5, 1.5 Hz, 1H), 7.63 (dd,
J¼7.0, 1.0 Hz, 1H), 7.92 (dd, J¼8.0, 1.0 Hz, 1H); 13C
NMR d: 52.1, 76.2, 85.4, 125.5, 126.6, 127.0, 127.3,
130.2, 130.9, 132.8, 145.1, 167.5; ESIHRMS, calcd for
C12H12O3: 227.0684 (M+Na), found: 227.0686.
4.4.2. 2-(2,5-Dihydrofuran-2-yl)phenol (47). Colorless oil;
1H NMR d: 4.79 (m, 1H), 4.86 (m, 1H), 6.07 (m, 3H), 6.86
(m, 2H), 7.02 (ddd, J¼7.5, 2.0, 1.0 Hz, 1H), 7.17 (dt, J¼7.5,
1.5 Hz, 1H), 7.98 (s, 1H); 13C NMR d: 75.5, 87.2, 117.1,
4.4.9. Methyl [2-(2,3-dihydrofuran-2-yl)phenyl]carba-
mate (54). Colorless oil; eluent: 1.5:1 (hexane/chloroform
with 1.5% EtOAc); H NMR d: 2.78 (m, 1H), 2.92 (m,
1

7834
D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
1H), 3.77 (s, 3H), 5.15 (q, J¼2.5 Hz, 1H), 5.53 (t, J¼
10.5 Hz, 1H), 6.45 (q, J¼2.5 Hz, 1H), 7.08 (t, J¼7.5 Hz,
1H), 7.23 (d, J¼7.0 Hz, 1H), 7.34 (dt, J¼7.5, 1.5 Hz, 1H),
7.38 (br s, 1H), 7.95 (br s, 1H); 13C NMR d: 35.0, 52.4,
82.8, 101.4, 121.9, 123.7, 127.7, 129.1, 129.3, 136.6,
144.6, 154.3; ESIHRMS, calcd for C12H13NO3: 242.0793
(M+Na), found: 242.0794.
d: 2.89 (m, 1H), 3.31 (m, 1H), 3.91 (s, 3H), 5.58 (m, 1H),
5.69 (dd, J¼10.0, 4.5 Hz, 1H), 6.23 (m, 1H), 7.29 (dt,
J¼7.5, 1.5 Hz, 1H), 7.49 (dt, J¼7.5, 1.5 Hz, 1H), 7.76 (dd,
J¼8.0, 1.0 Hz, 1H), 7.85 (dd, J¼8.0, 1.5 Hz, 1H); 13C
NMR d: 43.3, 47.9, 52.2, 120.4, 125.5, 126.9, 127.8,
128.2, 130.2, 132.6, 145.3, 167.9; ESIHRMS, calcd for
C12H12O2S: 221.0636 (M+H), found: 221.0635.
4.4.10. Methyl [2-(2,5-dihydrofuran-2-yl)phenyl]carba-
mate (55). Colorless oil; H NMR d: 3.77 (s, 3H), 4.79
4.4.16. Methyl 2-(2,5-dihydrothiophen-2-yl)benzoate
(62). Colorless oil; eluent: 1:1 (hexane/benzene); H NMR
1
1
(m, 2H), 5.89 (m, 1H), 6.04 (m, 1H), 6.13 (m, 1H), 7.04 (t,
J¼8.0 Hz, 1H), 7.12 (dd, J¼7.5, 1.5 Hz, 1H), 7.31 (dt,
J¼9.0, 1.5 Hz, 1H), 7.82 (br s, 1H), 7.93 (br s, 1H); 13C
NMR d: 52.3, 75.3, 85.9, 121.4, 123.4, 127.0, 127.7,
128.1, 128.9, 129.2, 137.1, 154.3; ESIHRMS, calcd for
C12H13NO3: 220.0974 (M+H), found: 220.0967.
d: 3.81–3.93 (m, 2H), 3.90 (s, 3H), 5.85 (m, 1H), 6.05 (m,
1H), 6.13 (m, 1H), 7.27 (dt, J¼6.5, 1.5 Hz, 1H), 7.48 (m,
2H), 7.85 (d, J¼9.0 Hz, 1H); 13C NMR d: 39.1, 52.2, 54.8,
126.9, 128.7, 128.7, 129.5, 130.2, 132.5, 132.5, 144.9,
167.8; ESIHRMS, calcd for C12H12O2S: 221.0636 (M+H),
found: 221.0636.
4.4.11. 2,3,4,5-Tetrahydro-2,5-epithio-1-benzoxepin (56).
Colorless oil; eluent: 1:1:1 (benzene/chloroform/hexane);
1H NMR d: 2.26–2.53 (m, 4H), 4.36 (d, J¼5.0 Hz, 1H),
6.19 (d, J¼4.5 Hz, 1H), 6.81 (m, 2H), 6.99 (dd, J¼7.5,
2.0 Hz, 1H), 7.13 (dt, J¼7.5, 1.5 Hz, 1H); 13C NMR d:
38.0, 40.4, 49.9, 86.9, 117.6, 120.1, 126.0, 128.6, 129.5,
151.3; ESIHRMS, calcd for C10H10OS: 179.0531 (M+H),
found: 179.0536.
4.4.17. Methyl [2-(2,3-dihydrothiophen-2-yl)phenyl]car-
bamate (63). Colorless oil; eluent: 1:1 (hexane/benzene
with 2% EtOAc); H NMR d: 2.97 (m, 1H), 3.17 (m, 1H),
3.77 (s, 3H), 5.09 (dd, J¼10.5, 8.0 Hz, 1H), 5.68 (m, 1H),
6.23 (m,1H), 7.06 (t, J¼7.0 Hz, 1H), 7.15 (br s, 1H), 7.29
(m, 2H), 7.81 (br s, 1H); 13C NMR d: 41.8, 50.2, 52.5,
122.3, 123.3, 124.4, 124.9, 128.5, 129.0, 132.0, 136.0,
154.5; ESIHRMS, calcd for C12H13NO2S: 258.0565
(M+Na), found: 258.0558.
1
4.4.12. 2-(2,5-Dihydrothiophen-2-yl)phenol (57). White
1
solid; mp 67–68 ꢀC (EtOAc/hexane); H NMR d: 3.95 (m,
4.4.18. Methyl [2-(2,5-dihydrothiophen-2-yl)phenyl]car-
bamate (64). Colorless oil; H NMR d: 3.75 (s, 3H), 3.94
1
2H), 5.57 (m, 1H), 5.85 (m, 1H), 6.03 (m, 1H), 6.40 (br s,
1H), 6.85 (d, J¼8.5 Hz, 1H), 6.88 (dt, J¼7.5, 1.0 Hz, 1H),
7.15 (dd, J¼7.5, 2.0 Hz, 1H), 7.19 (dt, J¼7.0, 1.5 Hz, 1H);
13C NMR d: 39.6, 56.0, 117.2, 120.7, 126.1, 129.2, 129.2,
129.4, 132.5, 155.0; Anal. Calcd for C10H10OS: C, 67.38;
H, 5.65. Found: C, 67.16; H, 5.44.
(br m, 2H), 5.50 (br s, 1H), 5.81 (m, 1H), 6.03 (m, 1H),
7.08 (t, J¼7.0 Hz, 1H), 7.20 (d, J¼7.5 Hz, 1H), 7.22 (br s,
1H), 7.27 (dt, J¼9.5, 2.0 Hz, 1H), 7.73 (br s, 1H); 13C
NMR d: 39.8, 52.4, 56.7, 123.5, 124.6, 128.6, 129.4,
129.5, 132.2, 136.2, 154.5; ESIHRMS, calcd for
C12H13NO2S: 258.0565 (M+Na), found: 258.0568.
4.4.13. 2-(2,3-Dihydrothiophen-2-yl)benzonitrile (58)
and 2-(2,3-dihydrothiophen-3-yl)benzonitrile (59). Com-
pounds 58 and 59 were obtained as a 1.4:1 inseparable mix-
ture with ESIHRMS, calcd for C11H9NS: 210.0354 (M+Na),
4.5. General protocol for aryl radical addition to
carbocyclic arenes
1
found: 210.0352. Compound 58 was characterized by H
A solution of aryl iodide (1.0 mmol), diphenyl diselenide
(62.0 mg, 0.2 mmol), and freshly distilled solvent (20 mL)
was sparged with argon for 45 min, followed by heating at
90 ꢀC (bath temperature) with stirring. A solution of AIBN
(33.0 mg, 0.2 mmol) and Bu3SnH (0.47 mL, 1.75 mmol) in
degassed solvent (10 mL) was added via syringe pump
over 16 h, after which heating was continued for 1 h, before
the reaction mixture was cooled to room temperature and
concentrated under vacuum. The residue was taken up in
acetonitrile (75 mL) and washed with hexane (4ꢂ25 mL)
(except Table 4 entries 1 and 4, which were purified without
acetonitrile/hexane workup). The acetonitrile phase was
concentrated and purified by silica gel chromatography.
NMR d: 2.89 (m, 1H), 3.35 (m, 1H), 5.27 (dd, J¼10.0,
5.5 Hz, 1H), 5.58 (m, 1H), 6.25 (m, 1H), 7.36 (m, 1H),
7.62 (dd, J¼7.5, 1.0 Hz, 1H), 7.75 (d, J¼8.0 Hz, 1H),
1
7.26–7.66 (1H). Compound 59 was characterized by H
NMR d: 3.13 (ddd, J¼11.0, 6.5, 2.0 Hz, 1H), 3.83 (dt,
J¼11.5, 2.0 Hz, 1H), 4.73 (m, 1H), 5.65 (m, 1H), 6.47 (m,
1H), 7.35 (t, J¼7.0 Hz, 1H), 7.53 (d, J¼8.0 Hz, 1H), 7.57
(t, J¼8.0 Hz, 1H), 7.66 (d, J¼7.5 Hz, 1H). Compounds 58
and 59 13C NMR d: 39.5, 43.6, 49.3, 51.0, 111.1, 111.7,
117.5, 117.8, 120.1, 123.9, 125.4, 127.6, 127.6, 127.7,
129.3, 132.7, 133.0, 133.32, 133.36, 146.6, 147.5.
4.4.14. 2-(2,5-Dihydrothiophen-2-yl)benzonitrile (60).
1
White solid; mp 80–81 ꢀC (EtOAc/hexane); H NMR d:
4.5.1. ( )-(4aR*,9bS*)-4a-Methoxy-3,4,4a,9b-tetrahydro-
dibenzofuran (66). Reaction solvent: anisole; colorless
oil; eluent: 1:4 (hexane/benzene); H NMR d: 1.82–1.88
(m, 1H), 2.14–2.18 (m, 2H), 2.42–2.46 (td, J¼13.0,
4.5 Hz, 1H), 3.39 (s, 3H), 3.71 (s, 1H), 5.73–5.79 (m, 2H),
6.86 (d, J¼8.0 Hz, 1H), 6.90 (t, J¼8.0 Hz, 1H), 7.16 (t,
J¼8.0 Hz, 1H), 7.20 (d, J¼7.5 Hz, 1H); 13C NMR d: 22.0,
27.8, 47.3, 49.5, 110.1, 111.6, 121.1, 124.3, 126.4, 126.9,
128.1, 130.3, 157.6; EIHRMS, calcd for C13H14O2:
202.0994 (M+), found: 202.0999.
3.93 (m, 1H), 4.03 (m, 1H), 5.70 (m, 1H), 5.78 (m, 1H),
6.08 (m, 1H), 7.32 (dt, J¼8.0, 1.5 Hz, 1H), 7.48 (dd,
J¼7.5, 1.0 Hz, 1H), 7.55 (dt, J¼7.5, 1.5 Hz, 1H), 7.62 (dd,
J¼7.5, 1.5 Hz, 1H); 13C NMR d: 40.3, 56.5, 111.5, 117.4,
127.7, 128.9, 130.6, 130.9, 133.1, 133.1, 147.3; Anal. Calcd
for C11H9NS: C, 70.55; H, 4.84. Found: C, 70.47; H, 4.88.
1
4.4.15. Methyl 2-(2,3-dihydrothiophen-2-yl)benzoate
(61). Colorless oil; eluent: 1:1 (hexane/benzene); H NMR
1

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7835
4.5.2. 2-(2-Methoxyphenyl)phenol (67). Reaction solvent:
anisole; white solid; mp 72 ꢀC, lit.73 73–74 ꢀC; spectro-
scopic data identical to literature values;73 1H NMR d:
3.91 (s, 3H), 6.29 (s, 1H), 7.02–7.08 (m, 3H), 7.14 (dt, J¼
7.5, 1.0 Hz, 1H), 7.29 (dd, J¼8.0, 1.5 Hz, 1H), 7.32 (dt,
J¼8.5, 1.5 Hz, 1H), 7.37 (dd, J¼8.0, 1.5 Hz, 1H), 7.42 (dt,
J¼8.0, 1.5 Hz, 1H).
4.5.9. 2-(4-Methoxyphenyl)aniline (74). Reaction solvent:
anisole; colorless oil; spectroscopic data identical to litera-
ture values;78 1H NMR d: 3.84 (s, 3H), 6.79 (dd, J¼8.0,
0.5 Hz, 1H), 6.84 (dt, J¼7.5, 1.0 Hz, 1H), 6.99 (d,
J¼8.5 Hz, 2H), 7.11–7.16 (m, 2H), 7.38 (d, J¼9.0 Hz, 2H).
4.5.10. 1-(2-Hydroxyphenyl)-2-chloro-cyclohexa-2,5-
diene (75). Reaction solvent: chlorobenzene; colorless oil;
eluent: 2:1:1 (hexane/benzene/chloroform); 1H NMR d:
2.93–2.98 (m, 2H), 4.42–4.45 (m, 1H), 5.12 (s, 1H), 5.74–
5.78 (m, 1H), 5.82–5.85 (m, 1H), 6.05 (m, 1H), 6.82 (d,
J¼8.5 Hz, 1H), 6.93 (t, J¼7.0 Hz, 1H), 7.15–7.18 (m, 2H);
13C NMR d: 28.2, 43.2, 116.4, 121.2, 122.9, 123.5, 127.1,
127.4, 128.5, 130.2, 131.9, 153.9; EIHRMS, calcd for
C12H11ClO: 206.0498 (M+), found: 206.0508.
4.5.3. 2-(4-Methoxyphenyl)phenol (68). Reaction solvent:
anisole; white solid; mp 60–62 ꢀC, lit.74 65–66 ꢀC; spectro-
scopic data identical to literature values;74 1H NMR d: 3.87
(s, 3H), 5.23 (s, 1H), 6.97–7.00 (m, 2H), 7.03 (d, J¼9.0 Hz,
2H), 7.22–7.26 (m, 2H), 7.40 (d, J¼9.0 Hz, 2H).
4.5.4. ( )-(4aR*,10bS*)-4a-Methoxy-3,4,4a,10b-tetra-
hydro-4H-dibenzo[b,d]pyran-6-one (69). Reaction sol-
vent: anisole; colorless oil; eluent: 1:9 (EtoAc/hexane);
1H NMR d: 1.68–1.74 (ddd, J¼17.5, 11.0, 6.0 Hz, 1H),
2.26–2.32 (m, 1H), 2.40–2.47 (m, 1H), 2.54–2.58 (ddd,
J¼13.5, 6.0, 2.0 Hz, 1H), 3.40 (s, 3H), 3.67 (m, 1H), 5.37–
5.40 (qd, J¼10.0, 2.0 Hz, 1H), 5.73–5.77 (m, 1H),
7.31 (dd, J¼7.5, 1.0 Hz, 1H), 7.38 (dt, J¼7.5, 1.0 Hz,
1H), 7.59 (dt, J¼7.5, 1.0 Hz, 1H), 8.10 (dd, J¼7.5, 1.0 Hz,
1H); 13C NMR d: 23.5, 28.0, 43.7, 49.3, 103.7, 123.3,
126.7, 126.8, 127.5, 128.0, 130.0, 134.5, 141.3, 164.2;
ESIHRMS, calcd for C14H14O3: 231.1016 (M+H), found:
231.1015.
4.5.11. 1-(2-Hydroxyphenyl)-3-chloro cyclohexa-2,5-
diene (76). Reaction solvent: chlorobenzene; colorless oil;
eluent: 2:1:1 (hexane/benzene/chloroform); 1H NMR d:
3.02–3.05 (m, 2H), 4.41–4.45 (m, 1H), 5.03 (br s, 1H),
5.78–5.81 (m, 1H), 5.83–5.86 (m, 1H), 5.90–5.91 (m, 1H),
6.77–6.78 (dd, J¼8.0, 1.0 Hz, 1H), 6.90–6.93 (dt, J¼7.5,
1.5 Hz, 1H), 7.10–7.15 (m, 2H); 13C NMR d: 33.1, 39.3,
115.9, 121.2, 123.8, 124.8, 126.7, 128.2, 128.3, 129.5,
129.9, 153.4; ESIHRMS, calcd for C12H11ClO: 205.0420
(MꢃH), found: 205.0411.
4.5.12. 2-(2-Hydroxyphenyl)benzonitrile (77). Reaction
solvent: benzonitrile; white solid; mp 92–93 ꢀC, lit.79 71–
73 ꢀC, eluent: 1:19 (EtOAc/hexane); spectroscopic data
4.5.5. 2-(2-Methoxyphenyl)benzoic acid (70). Reaction
solvent: anisole; white solid; mp 150–152 ꢀC, lit.75 149–
152 ꢀC; spectroscopic data identical to literature values;75
1H NMR d: 3.71 (s, 3H), 6.88 (d, J¼8.0 Hz, 1H), 7.05 (dt,
J¼7.5, 1.0 Hz, 1H), 7.28 (dd, J¼7.0, 1.5 Hz, 1H), 7.32–
7.36 (m, 2H), 7.42 (dt, J¼8.0, 1.5 Hz, 1H), 7.59 (dt,
J¼7.5, 1.5 Hz, 1H), 7.94 (dd, J¼8.0, 1.5 Hz, 1H).
1
identical to literature values; H NMR d: 7.32–7.38 (m,
2H), 7.48 (dt, J¼8.5, 1.5 Hz, 1H), 7.58 (dt, J¼8.0, 0.5 Hz,
1H), 7.82 (dt, J¼8.0, 1.5 Hz, 1H), 8.06 (dd, J¼7.5, 1.0 Hz,
1H), 8.12 (d, J¼8.0 Hz, 1H), 8.40 (dd, J¼7.5, 1.0 Hz, 1H);
13C NMR d: 117.8, 118.1, 121.3, 121.7, 122.8, 124.6,
128.9, 130.5, 130.6, 134.8, 134.7, 151.3, 161.2; ESIHRMS,
calcd for C13H9NO: 196.0757 (M+H), found: 196.0756.
4.5.6. 2-(4-Methoxyphenyl)benzoic acid (71). Reaction
solvent: anisole; white solid; mp 140–141 ꢀC, lit.76 140–
143 ꢀC; spectroscopic data identical to literature values;76
1H NMR d: 3.85 (s, 3H), 6.93 (d, J¼9.0 Hz, 2H), 7.28 (d,
J¼9.0 Hz, 2H), 7.35 (dd, J¼8.0, 2.0 Hz, 1H), 7.40 (dt, J¼
8.0, 1.0 Hz, 1H), 7.54 (dt, J¼8.5, 1.0 Hz, 1H), 7.93 (dd,
J¼8.5, 1.5 Hz, 1H).
4.5.13. 4-(2-Hydroxyphenyl)benzonitrile (78). Reaction
solvent: benzonitrile; white solid; mp 111–113 ꢀC, lit.80
111–112 ꢀC; spectroscopic data identical to literature
1
values; H NMR d: 5.13 (s, 1H), 6.95 (dd, J¼8.0, 0.5 Hz,
1H), 7.04 (t, J¼8.0 Hz, 1H), 7.26–7.32 (m, 2H), 7.67 (d,
J¼8.5 Hz, 2H), 7.74 (d, J¼8.5 Hz, 2H).
4.5.7. 2-(2-Methoxyphenyl)aniline (72). Reaction solvent:
anisole; yellowish solid; mp 65–67 ꢀC, lit.77 80 ꢀC; spectro-
scopic data identical to literature values;77 1H NMR d: 3.52
(br s, 2H), 3.82 (s, 3H), 6.80 (dd, J¼8.5, 1.5 Hz, 1H), 6.85
(dt, J¼7.0, 1.0 Hz, 1H), 7.01 (d, J¼9.0 Hz, 1H), 7.05 (dt,
J¼7.5, 1.0 Hz, 1H), 7.12 (dd, J¼7.5, 1.5 Hz, 1H), 7.18
(dt, J¼8.0, 2.0 Hz, 1H), 7.27 (dd, J¼7.5, 2.0 Hz, 1H), 7.37
(dt, J¼8.5, 2.0 Hz, 1H).
4.5.14. 3-(2-Hydroxyphenyl)benzonitrile (79). Reaction
solvent: benzonitrile; colorless oil; spectroscopic data iden-
tical to literature values;79 1H NMR d: 4.99 (s, 1H), 6.95 (dd,
J¼8.0, 1.0 Hz, 1H), 7.04 (dt, J¼7.5, 1.0 Hz, 1H), 7.25–7.31
(m, 2H), 7.56 (t, J¼8.0 Hz, 1H), 7.66 (tt, J¼8.0, 1.5 Hz, 1H),
7.78 (tt, J¼7.5, 1.5 Hz, 1H), 7.85 (t, J¼2.0 Hz, 1H).
4.5.15. 1-(2-Hydroxyphenyl)-1,4-dihydronaphthalene
(80). Reaction solvent: benzene (80 equiv of naphthalene
in benzene); colorless oil; eluent: 1:1 (hexane/benzene);
1H NMR d: 3.53–3.58 (m, 2H), 4.86 (m, 1H), 5.00 (s, 1H),
5.98–6.01 (m, 1H), 6.11–6.14 (m, 1H), 6.79 (dd, J¼8.0,
1.5 Hz, 1H), 6.90 (dt, J¼7.0, 1.0 Hz, 1H), 7.05 (d,
J¼8.0 Hz, 1H), 7.10–7.19 (m, 5H); 13C NMR d: 29.7,
41.3, 116.6, 120.9, 125.3, 126.6 (2C), 128.1, 128.3, 128.4,
129.0, 130.6, 130.7, 133.3, 136.0, 153.8; ESIHRMS, calcd
for C16H14O: 221.0966 (MꢃH), found: 221.0961.
4.5.8. 2-(3-Methoxyphenyl)aniline (73). Reaction solvent:
anisole; yellowish oil; eluent: 1:19 (EtoAc/hexane); 1H
NMR d: 3.83 (s, 3H), 6.80 (d, J¼7.5 Hz, 1H), 6.85 (dt,
J¼7.0, 1.0 Hz, 1H), 6.90 (ddd, J¼8.5, 2.5, 1.0 Hz, 1H),
7.00 (t, J¼2.0 Hz, 1H), 7.05 (td, J¼7.5, 1.0 Hz, 1H), 7.14–
7.19 (m, 2H), 7.36 (t, J¼8.0 Hz, 1H); 13C NMR d: 55.3,
113.0, 114.5, 115.9, 118.9, 121.4, 127.8, 128.6, 129.8,
130.3, 140.8, 142.9, 159.9; ESIHRMS, calcd for
C13H13NO: 200.1070 (M+H), found: 200.1069.

7836
D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7. The rate constants for trapping of primary alkyl radicals by
PhSeH and Bu3SnH at 25 ꢀC are, respectively, 1ꢂ109 and
4.5.16. 1-(2-Hydroxyphenyl)-1,2-dihydronaphthalene
(81) and 2-(2-hydroxyphenyl)-1,2-dihydronaphthalene
(82). Compounds 81 and 82 were obtained as a 1.4:1 mix-
ture. Reaction solvent: benzene (80 equiv of naphthalene
in benzene); eluent: 1:1 (hexane/benzene); Characteristic
1H NMR peaks of compound 81 d: 2.61–2.71 (m, 2H),
4.47–4.51 (dd, J¼10.5, 8.0 Hz, 1H), 4.81 (s, 1H), 6.03–
2ꢂ106 Mꢃ1 sꢃ1 8,9
.
8. Newcomb, M.; Choi, S.-Y.; Horner, J. H. J. Org. Chem. 1999,
64, 1225–1231.
9. Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem.
Soc. 1981, 103, 7739–7742.
10. Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25–36.
1
6.07 (m, 1H), 6.57 (d, J¼10.0 Hz, 1H); Characteristic H
´
11. Martınez-Barrasa, V.; Garcia de Viedma, A.; Burgos, C.;
NMR peaks of compound 82 d: 3.03 (dd, J¼16.0, 12.0 Hz,
1H), 3.13 (dd, J¼15.5, 7.5 Hz, 1H), 4.09–4.13 (m, 1H),
4.96 (s, 1H), 6.09–6.11 (dd, J¼9.5, 3.5 Hz, 1H), 6.68–6.70
Alvarez-Builla, J. Org. Lett. 2000, 2, 3933–3935.
12. Studer, A.; Bossart, M. Radicals in Organic Synthesis; Renaud,
P., Sibi, M., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2,
pp 62–80.
13. Beckwith, A. L. J.; Bowry, V. W.; Bowman, W. R.; Mann, E.;
Parr, J.; Storey, J. M. D. Angew. Chem., Int. Ed. 2004, 43,
95–98.
14. Curran, D. P.; Yu, H.; Liu, H. Tetrahedron 1994, 50, 7343–
7366.
15. Curran, D. P.; Liu, H. J. Chem. Soc., Perkin Trans. 1 1994,
1377–1393.
1
(dd, J¼9.5, 2.5 Hz, 1H); 81 and 82 H NMR d: 6.80–6.81
(dd, J¼8.0, 0.5 Hz, 1H), 6.84–6.85 (dd, J¼8.0, 1.0 Hz
1H), 6.90–6.93 (m, 3H), 7.06–7.26 (m, 11H); 13C NMR d:
30.0, 34.6, 35.3, 38.4, 115.8, 116.1, 121.05, 121.08, 126.2,
126.4, 126.7, 127.2, 127.3, 127.5, 127.6, 127.7, 127.81,
127.83, 127.88, 127.89, 129.0, 129.1, 129.8, 130.24,
130.28, 131.2, 133.3, 134.4, 134.6, 136.2, 153.2, 153.3;
ESIHRMS, calcd for C16H14O: 221.0966 (MꢃH), found:
221.0961.
16. Engel, P. S.; Wu, W.-X. J. Am. Chem. Soc. 1989, 111, 1830–
1835.
4.6. ( )-(3S*,4R*)-Allyl-3-(2-hydroxyphenyl)-4-
methoxycyclohexene (83)
17. For an excellent overview of the large body of early work
on the oxidative radical arylation of arenes, including
relative rates and regioselectivities see: Williams, G. H.
Homolytic Aromatic Substitution; Pergamon: New York, NY,
1960.
18. Preliminary communications: (a) Crich, D.; Patel, M.
Heterocycles 2004, 64, 499–564; (b) Crich, D.; Patel, M.
Org. Lett. 2005, 7, 3625–3628.
19. Harrowven, D. C.; Sutton, B. J. Progress in Heterocyclic
Chemistry; Gribble, G. W., Joule, J. A., Eds.; Elsevier:
Amsterdam, 2005; Vol. 16.
20. Abramovitch, R. A.; Saha, M. J. Chem. Soc. 1964, 2175–2187.
21. Abramovitch, R. A.; Saha, M. J. Chem. Soc. B 1966, 733–739.
22. Vernin, G.; Dou, H.-J. M. C. R. Acad. Sci. 1967, 265C, 828–
830.
To a solution of compound 66 (50 mg, 0.25 mmol) and allyl-
trimethylsilane (0.039 mL, 0.25 mmol) in CH2Cl2 (3.0 mL)
under argon at ꢃ78 ꢀC was added TiCl4 (0.027 mL,
0.25 mmol). The reaction mixture was quenched with satu-
rated NaHCO3 after 15 min of stirring and extracted with di-
ethyl ether (3ꢂ20 mL). The combined organic layer was
dried (Na2SO4), and the solvent was removed under reduced
pressure. Purification by silica gel column chromatography
(EtOAc/hexane) afforded compound 83 in 84%, yield. Col-
orless oil; 1H NMR d: 1.78–1.83 (m, 1H), 1.90–1.95 (m, 1H),
2.11–2.16 (m, 1H), 2.23–2.30 (m, 1H), 2.36–2.48 (dq,
J¼14.0, 7.5 Hz, 2H), 3.28 (s, 3H), 3.63 (t, J¼2.5 Hz, 1H),
5.13–5.19 (m, 2H), 5.50–5.53 (qd, J¼7.5, 2.5 Hz, 1H),
5.84–5.89 (m, 2H), 6.83 (dt, J¼7.5, 1.5 Hz, 1H), 6.90 (dd,
J¼8.0, 1.0 Hz, 1H), 7.09 (dd, J¼7.5, 2.0 Hz, 1H), 7.17 (dt,
J¼8.0, 2.5 Hz, 1H), 8.34 (br s, 1H); 13C NMR d: 22.9,
26.3, 38.8, 48.0, 48.8, 79.7, 118.0, 119.1, 119.6, 126.8,
127.6, 127.8, 128.5, 132.4, 133.2, 156.5; EIHRMS, calcd
for C16H20O2: 244.1463 (M+), found: 244.1460.
23. Further data on the relative rates of addition of substituted
phenyl radicals to pyridines may be found in Ref. 17 and in
24
€
the Landolt-Bornstein series.
24. Lorand, J. P. Landolt-Bo€rnstein New Series; Fischer, H., Ed.;
Springer: Berlin, 1984; Vol. 13a, pp 202–248.
25. Hey, D. H.; Shingleton, D. A.; Williams, G. H. J. Chem. Soc.
1963, 5612–5619.
26. Abramovitch, R. A.; Saha, M. Can. J. Chem. 1966, 44, 1765–
1771.
Acknowledgements
27. Except in solvents such as acetonitrile, when a significant pref-
erence for the para-position was reported. Gurczynski, M.;
Tomasik, P. Org. Prep. Proced. Int. 1991, 23, 438–441.
We thank the NSF (CHE 9986200) for partial support of this
work and Bhushan Surve for the X-ray crystal structure.
´
´
28. Nun˜ez, A.; Sanchez, A.; Burgos, C.; Alvarez-Builla, J.
Tetrahedron 2004, 60, 6217–6224.
References and notes
29. Fowler, F. W. Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984;
Vol. 2, pp 365–394.
30. Lounasmaa, M.; Tolvanen, A. Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V.,
Eds.; Pergamon: Oxford, 1996; Vol. 5, pp 135–165.
31. Pausacker, K. H. Aust. J. Chem. 1958, 11, 200–210.
32. Vernin, G.; Dou, H. J. M.; Metzger, J. Bull. Soc. Chim. Fr. 1971,
2612–2616.
1. Crich, D.; Hwang, J.-T. J. Org. Chem. 1998, 63, 2765–2770.
2. Crich, D.; Yao, Q. J. Org. Chem. 1995, 60, 84–88.
3. Crich, D.; Jiao, X.-Y.; Yao, Q.; Harwood, J. S. J. Org. Chem.
1996, 61, 2368–2373.
4. The BDE’s for Me3Sn-H and PhSe-H are 78 and 78ꢁ4 cal
molꢃ1, respectively.5,6
5. Laarhoven, L. J. J.; Mulder, P.; Wayner, D. D. M. Acc. Chem.
Res. 1999, 32, 342–349.
6. Leeck, D. T.; Li, D. T.; Chyall, L. J.; Kenttamaa, H. I. J. Phys.
Chem. 1996, 100, 6608–6611.
33. Dyall, L. K.; Pullin, C. J. Aust. J. Chem. 1979, 32, 345–352.
34. Vernin, G.; Dou, H. J. M.; Loridan, G.; Metzger, J. Bull. Soc.
Chim. Fr. 1970, 2705–2707.

D. Crich, M. Patel / Tetrahedron 62 (2006) 7824–7837
7837
35. Alcock, N. W.; Brown, J. M.; Hulmes, D. I. Tetrahedron:
Asymmetry 1993, 4, 743–756.
36. Barton, D. H. R.; Brewster, A. G.; Ley, S. V.; Read, C. M.;
Rosenfeld, M. N. J. Chem. Soc., Perkin Trans. 1 1981, 1473–
1476.
37. Benati, L.; La Barba, N.; Tiecco, M.; Tundo, A. J. Chem. Soc. B
1969, 1253–1256.
38. Camaggi, C. M.; Leardini, R.; Tiecco, M.; Tundo, A. J. Chem.
Soc. B 1969, 1251–1253.
59. Edwards, M. L.; Stemerick, D. M.; Sabol, J. S.; Diekema,
K. A.; Dinerstein, R. J. J. Med. Chem. 1994, 37, 4357–4362.
60. Sledeski, Y. M.; McGarry, D. G.; Green, D. M.; Mason, H. J.;
Becker, M. R.; Davis, R. S.; Ewing, W. R.; Dankulich, W. P.;
Manetta, V. E.; Morris, R. L.; Spada, A. P.; Cheney, D. L.;
Brown, K. D.; Colussi, D. J.; Chu, V.; Heran, C. L.; Morgan,
S. R.; Bentley, R. G.; Leadley, R. J.; Maignan, S.; Guilloteau,
J. P.; Dunwiddie, C. T.; Pauls, H. W. J. Med. Chem. 1999, 42,
3572–3587.
´
39. Walling, C. Tetrahedron 1985, 41, 3887–3900.
40. Kita, Y.; Gotanda, K.; Sano, A.; Oka, M.; Murata, K.; Suemua,
M.; Matsugi, M. Tetrahedron Lett. 1997, 38, 8345–8348.
41. Kita, Y.; Matsugi, M. Radicals in Organic Synthesis; Sibi,
M. P., Renaud, P., Eds.; Wiley-VCH: Weinheim, 2001;
Vol. 1, pp 1–10.
42. Griller, D.; Nonhebel, D. C.; Walton, J. C. J. Chem. Soc., Perkin
Trans. 2 1984, 1817–1821.
43. Korth, H.-G.; Sustmann, R. Tetrahedron Lett. 1985, 26, 2551–
2554.
44. Korth, H.-G.; Lommes, P.; Sustmann, R. J. Am. Chem. Soc.
1984, 106, 663–668.
45. Edge, D. J.; Kochi, J. K. J. Chem. Soc., Perkin Trans. 2 1973,
182–190.
46. 96.06ꢁ0.15, 93.9ꢁ2, and 93.9ꢁ2 kcal molꢃ1, respectively.
Luo, Y.-R. Handbook of Bond Dissociation Energies in
Organic Compounds; CRC: Boca Raton, FL, 2003.
61. Boy, P.; Combellas, C.; Thiebault, A.; Amatore, C.; Jutland, A.
Tetrahedron Lett. 1992, 33, 491–494.
62. Tingoli, M.; Tiecco, M.; Testaferri, L.; Andrenacci, R.;
Balducci, R. J. Org. Chem. 1993, 58, 6097–6102.
63. Novak, I.; Ng, S.-C.; Mok, C.-Y.; Huang, H.-H.; Fang, J.;
Wang, K. K.-T. J. Chem. Soc., Perkin Trans. 2 1994, 1771–
1775.
64. Abbotto, A.; Bradamante, S.; Facchetti, A.; Pagani, G. A.
J. Org. Chem. 1997, 62, 5755–5765.
65. Molina, P.; Lorenzo, A.; Aller, E. Tetrahedron 1992, 48, 4601–
4616.
66. Rebstock, A.-S.; Mongin, F.; Trecourt, F.; Quequiner, G. Org.
Biomol. Chem. 2003, 1, 3064–3068.
67. Mongin, F.; Mojovic, L.; Guillamet, B.; Trecourt, F.;
Quequiner, G. J. Org. Chem. 2002, 67, 8991–8994.
68. Barros, A. I. R. N. A.; Silva, A. M. S. Tetrahedron Lett. 2003,
44, 5893–5896.
ˆ
47. Ito, R.; Migita, T.; Morikawa, N.; Simamura, O. Tetrahedron
1965, 21, 955–961.
69. Nelson, J. T.; Davis, R. S. Magn. Reson. Chem. 1991, 29,
513–517.
48. Pyror, W. A.; Echols, J. T.; Smith, K. J. Am. Chem. Soc. 1966,
88, 1189–1199.
49. Scaiano, J. C.; Stewart, L. C. J. Am. Chem. Soc. 1983, 105,
3609–3614.
50. Levy, A.; Meyerstein, D.; Ottolenghi, M. J. Phys. Chem. 1973,
77, 3044–3047.
51. Kryger, R. G.; Lorand, J. P.; Stevens, N. R.; Herron, N. R.
J. Am. Chem. Soc. 1977, 99, 7589–7600.
52. Dannley, R. l.; Gregg, E. C. J. Am. Chem. Soc. 1954, 76, 2997–
3000.
70. Xu, Z.; Lu, X. J. Org. Chem. 1998, 63, 5031–5041.
71. Tachikawa, R.; Wachi, K.; Terada, A. Heterocycles 1981, 16,
1165–1168.
72. Holzapfel, C. W.; Williams, D. B. G. Synth. Commun. 1994, 24,
2139–2146.
73. Baret, P.; Beguin, C.; Gaude, D.; Gellon, G.; Mourral, C.
Tetrahedron 1994, 50, 2077–2094.
74. Abramovitch, R. A.; Alvernhe, G.; Bartnik, R.; Dassanayake,
N. L.; Inbasekara, M. N.; Kato, S. J. Am. Chem. Soc. 1981,
103, 4558–4565.
53. Dickerman, S. C.; Vermont, G. B. J. Am. Chem. Soc. 1962, 84,
4150–4151.
54. Bonnier, J.-M.; Rinaudo, J.; Bouvier, C. Bull. Soc. Chim. Fr.
1967, 4067–4069.
55. Dix, I.; Doll, C.; Hopf, H.; Jones, P. G. Eur. J. Org. Chem. 2002,
2547–2556.
56. Abramovitch, R. A.; Shinkai, I. J. Am. Chem. Soc. 1974, 96,
5265–5267.
75. Xia, M.; Chen, Z. Synth. Commun. 2000, 30, 63–68.
76. Tao, B.; Goel, S. C.; Singh, J.; Boykin, D. W. Synthesis 2002,
1043–1046.
77. Downie, I. M.; Heaney, H.; Kemp, G.; King, D.; Wosley, M.
Tetrahedron 1992, 48, 4005–4016.
78. Takeuchi, H.; Taniguchi, T.; Ueda, T. J. Chem. Soc., Perkin
Trans. 2 2000, 295–300.
79. Rossiter, B. E.; Reese, S. L.; Morgan, S. R.; Malik, A.;
Bradshaw, J. S.; Lee, M. L. J. Microcolumn Sep. 1992, 4,
521–527.
57. Ishikura, M.; Ohta, T.; Terashima, M. Chem. Pharm. Bull.
1985, 33, 4755–4763.
58. Malmberg, H.; Nilsson, M. Tetrahedron 1986, 42, 3981–3986.
80. Haga, N.; Takayanagi, H. J. Org. Chem. 1996, 61, 735–745.