Synthesis of polycyclic xanthenes and furans via palladium-catalyzed cyclization of polycyclic aryltriflate esters

Article abstract of DOI:10.1016/S0040-4020(02)00534-3

Palladium-catalyzed cyclization of polycyclic aromatic o-(arylmethyl)phenol triflate esters takes place with unexpected sulfur-oxygen bond cleavage to furnish polycyclic xanthenes. These are the first examples of Pd-catalyzed cross-coupling of aryl triflate esters with arenes to form diaryl ethers. In contrast, analogous palladium-catalyzed cyclization of polycyclic o-(aryloxy)phenol triflate esters proceeds via a mechanism that involves conventional carbon-oxygen bond cleavage to furnish diaryl furans.

Full text of DOI:10.1016/S0040-4020(02)00534-3

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 5927±5931
Synthesis of polycyclic xanthenes and furans via palladium-
catalyzed cyclization of polycyclic aryltri¯ate esters
Ji-Quan Wang and Ronald G. Harveyp
Ben May Institute for Cancer Research, University of Chicago, MC 6027, 5841 South Maryland Avenue, Chicago, IL 60637, USA
Received 19 March 2002; accepted 21 May 2002
AbstractÐPalladium-catalyzed cyclization of polycyclic aromatic o-(arylmethyl)phenol tri¯ate esters takes place with unexpected sulfur±
oxygen bond cleavage to furnish polycyclic xanthenes. These are the ®rst examples of Pd-catalyzed cross-coupling of aryl tri¯ate esters with
arenes to form diaryl ethers. In contrast, analogous palladium-catalyzed cyclization of polycyclic o-(aryloxy)phenol tri¯ate esters proceeds
via a mechanism that involves conventional carbon±oxygen bond cleavage to furnish diaryl furans. q 2002 Elsevier Science Ltd. All rights
reserved.
Administration of coal tar to mice in the diet results in
the formation of DNA adducts in mouse lung and a high
incidence of lung tumors.1,2 A principal component of tar
responsible for formation of the DNA adducts has recently
been identi®ed as 7H-benzo[c]¯uorene (BcF).3 This ®nding
has important implications for cancer in human populations
because BcF is a relatively common environmental pollu-
tant produced by incomplete combustion of fossil fuels, and
BcF is also a component of mainstream cigarette smoke.4 In
connection with studies to identify the active metabolites of
BcF that bind to DNA,5 we required practical syntheses of
BcF and 3-methoxy-BcF.6
bis(triphenylphosphine)palladium(II) chloride was employed
by Rice and Cai11 as a key step in the synthesis of several
benzo¯uoranthenes. Their synthesis resembles the proposed
synthesis of BcF in that a ®ve-membered ring is formed in
the coupling step, but differs in that it entails cyclization to a
peri ring position of an adjacent aromatic ring, whereas the
synthesis of BcF involves reaction at an ortho position of the
Synthesis of BcF was accomplished via alkylation of the
enamine of cyclohexanone by 2-bromomethylnaphthalene
(Scheme 1) to furnish 2-(2-naphthylmethyl)cyclohexanone
(1), followed by acid-catalyzed cyclodehydration and
dehydrogenation.7,8 Because the yield in the cyclization
step was only moderate, we investigated a modi®cation of
this method. The alternative approach entailed conversion
of 1 to the corresponding phenol derivative (2a) and
cyclization of its tri¯ate ester derivative (2b) by palladium-
catalyzed intramolecular coupling.
1. Results and discussion
Although palladium-catalyzed coupling of aryl halides with
arenes has numerous synthetic applications,9 analogous
coupling of aryl tri¯ates with arenes is less well known.10
Intramolecular aryl tri¯ate±arene coupling mediated by
Keywords: palladium-catalyzed coupling; polycyclic xanthenes; polycyclic
furans.
p
Corresponding author. Tel.: 11-773-702-6998; fax: 11-773-702-6260;
e-mail: rharvey@benmay.bsd.uchicago.edu
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00534-3

5928
J.-Q. Wang, R. G. Harvey / Tetrahedron 58 (2002) 5927±5931
same aromatic ring. The geometries of the ®ve-membered
rings that are formed in these cases are signi®cantly
different.
Dehydrogenation of 2-(2-naphthylmethyl)cyclohexanone
(1) over a 10% palladium±charcoal catalyst in re¯uxing
triglyme at 2408C gave 2-(2-naphthylmethyl)phenol (2a)
(Scheme 1). The latter was converted to the corresponding
tri¯ate ester (2b) by treatment with tri¯uoromethanesulfonic
acid anhydride and 2,6-lutidine. Reaction of 2b, LiCl, and
DBU with bis(triphenylphosphine)palladium(II) chloride
(0.1 equiv.) in DMF at 1458C gave a white solid, mp
88±898C, whose 1H and 13C NMR spectra and other proper-
ties were inconsistent with the structure of BcF, the
expected product of palladium-catalyzed cyclization. The
novel product was identi®ed as 7H-benzo[c]xanthene (3),
a polycyclic aromatic compound with one more oxygen
1
atom [FAB MS m/z 232 (M1)]. The H and 13C NMR
spectra of 3 were in agreement with this structural assign-
ment as were its melting point (88±898C; lit12 90±918C) and
elemental analysis. Evidently, cyclization of the tri¯ate ester
(2b) took place with cleavage of the sulfur±oxygen bond
rather than the carbon±oxygen bond. This mode of bond
cleavage was not observed previously in the analogous
cyclization of tri¯ate esters to form benzo¯uoranthenes.11
As far as we are aware, this is the ®rst example of
palladium-catalyzed cross-coupling of an aryl tri¯ate ester
with an arene to form a diaryl ether product.
We also examined whether aryloxyphenol tri¯ate esters
might participate in palladium-catalyzed reactions to afford
cyclized products with one or two oxygen atoms in
the saturated ring. 2-(2-Naphthoxy)phenol tri¯ate (14c)
was prepared (Scheme 2) by base-catalyzed reaction of
2-¯uorobenzaldehyde with 2-naphthol to yield the aryloxy-
benzaldehyde derivative (13), followed by Baeyer±Villiger
oxidation with m-chloroperbenzoic acid to furnish
2-(2-naphthyloxy)phenol formate (14a). The latter was
hydrolyzed to the free phenol (14b) which was converted
to the tri¯ate ester (14c) by treatment with tri¯ic acid
anhydride in the presence of lutidine. The tri¯ate ester of
2-(phenoxy)phenol (15c) was similarly prepared from
analogous reaction of 2-¯uorobenzaldehyde and phenol.
In view of the novelty of the synthesis of 7H-benzo[c]-
xanthene, we investigated the utility of the method for the
synthesis of other oxygen-containing heterocyclic poly-
cyclic aromatic compounds. Ketones 4±6 were prepared
by alkylation of the enamine of cyclohexanone by 2-bromo-
methylnaphthalene, 9-bromomethylphenanthrene, and ben-
zyl bromide, respectively. The ketones 4±6 were converted
to the corresponding tri¯ate esters (7b±9b) via dehydro-
genation over a 10% palladium±charcoal catalyst in
triglyme followed by treatment of the phenolic products
(7a±9a) with tri¯uoromethanesulfonic anhydride in the
presence of 2,6-lutidine. Palladium-catalyzed reaction of
tri¯ate esters 7b and 8b under the same conditions as 2b
furnished as the principal products 12H-benzo[a]xanthene
(11) and 14H-dibenzo[a,c]xanthene (12), respectively.
However, analogous reaction of the tri¯ate ester 9b failed
to afford xanthene or ¯uorene, the products anticipated to
arise via either mode of cyclization. Instead, there was
obtained an insoluble residue of indeterminate structure.
Analogous reaction of 2-hydroxybiphenyl tri¯ate (10b)
also failed to afford cyclized products.
Palladium-catalyzed reaction of the tri¯ate esters 14c and
15c under the same conditions employed for 2b provided
the corresponding polycyclic aromatic furan derivatives,
benzo[b]naphtho[2,3-d]furan (16) and dibenzofuran (17),
in yields of 96 and 80%, respectively. In both these
Scheme 2.

J.-Q. Wang, R. G. Harvey / Tetrahedron 58 (2002) 5927±5931
5929
examples, cyclized products were formed via exclusive
carbon±oxygen bond cleavage. The related polycyclic
aromatic dioxanes expected to arise from the alternative
mode of bond cleavage were not detected. It is also worthy
of note that cyclization of 14c took place regioselectively to
the 3-position of the naphthalene ring rather than to the
usually more reactive 1-position, as observed in cyclization
of 2b.
2.1.1. 2-(9-Phenanthrylmethyl)cyclohexanone (5). To a
solution of 9-(bromomethyl)phenanthrene (5.00 g, 18.4
mmol) in dry dioxane (30 mL) was added 1-pyrrolidino-1-
cyclohexene (3.0 mL, 18.6 mmol). The solution was heated
at re¯ux for 18 h. Then water (10 mL) was added, and
re¯uxing was continued for another 2 h. After cooling to
room temperature, the solution was transferred to a sepa-
ratory funnel and ether (500 mL) and 5% HCl (300 mL)
were added. The organic layer was washed with 5% HCl,
5% aqueous NaHCO3 solution and water, dried over
MgSO4, and evaporated to dryness. The residue was
chromatographed on a silica gel column eluted with
benzene±hexane (1:1) to afford 5 (4.55 g, 86%) as a white
In summary, palladium-catalyzed cyclization of arylmethyl-
phenol tri¯ate esters (2b, 7, 8) takes place with preferential
sulfur±oxygen bond cleavage to furnish polycyclic
xanthene compounds, 7H-benzo[c]xanthene (3), 12H-ben-
zo[a]xanthene (11) and 14H-dibenzo[a,c]xanthene (12). In
contrast, analogous palladium-catalyzed reactions of the
tri¯ate esters of aryloxyphenols (14c and 15c) occur with
preferential carbon±oxygen bond cleavage to furnish
polycyclic furans, benzo[b]naphtho[2,3-d]furan (16) and
dibenzofuran (17). These reactions provide convenient
synthetic access to polycyclic xanthenes and furan
compounds.
1
solid, mp 100±1018C: H NMR (CDCl3) d 8.72±8.75 (m,
1), 8.62±8.66 (m, 1), 7.98±8.02 (m, 1), 7.81±7.85 (m, 1),
7.56±7.68 (m, 5), 3.96 (dd, 1, Jˆ10.42 Hz), 1.41±2.81 (m,
10); 13C NMR (CDCl3) d 212.3, 134.2, 131.5, 131.0, 130.7,
129.6, 128.0, 127.7, 126.6, 126.5, 126.1, 126.0, 124.2,
123.3, 122.3, 50.7, 42.11, 33.8, 32.8, 27.9, 24.9; FAB MS
m/z 288 (M1). Anal. Calcd for C21H20O: C, 87.46; H, 6.99.
Found: C, 87.74; H, 7.22.
Details of the mechanisms of these reactions are not known.
We are grateful to a reviewer for pointing out that ortho-
palladation of unsubstituted diary ethers is an established
reaction14 and the intermediates involved may be the same
as in the synthesis of the furans whose synthesis is reported
herein. More extensive investigation will be required to
determine the details of the mechanisms and the roles of
the factors involved in determining the mode of bond
cleavage and the direction of cyclization.
2.1.2. 2-(2-Naphthylmethyl)phenol (2a). To a solution of 1
(1.00 g, 4.2 mmol) in dry triglyme (20 mL) was added 10%
Pd/C (500 mg). The mixture was heated to 2308C under
argon for 14 h. After cooling, the mixture was diluted
with ether and ®ltered. The ®ltrate was washed three
times with water. The ether layer was dried over MgSO4,
and evaporated to dryness. The crude product was puri®ed
by chromatography on a column of silica gel eluted with
EtOAc±hexane (1:15) to afford 2a (810 mg, 83%) as a
1
white solid, mp 58±598C: H NMR (CDCl3) d 7.75±7.82
(m, 3), 7.66 (s, 1), 7.41±7.48 (m, 2), 7.37 (d, 1, Jˆ8.45 Hz),
7.13±7.19 (m, 2), 6.91 (t, 1, Jˆ7.42 Hz), 6.79 (d, 1, Jˆ
7.88 Hz), 4.76 (s, 1, OH), 4.16 (s, 2, CH2); 13C NMR
(CDCl3) d 153.7, 137.4, 133.6, 132.2, 131.0, 128.3, 127.9,
127.6, 127.5, 127.3, 126.8, 126.0, 125.4, 121.0, 115.7, 36.5;
FAB MS m/z 234 (M1). Anal. Calcd for C17H14O: C, 87.15;
H, 6.02. Found: C, 87.26; H, 6.22.
2. Experimental
2.1. Materials and methods
2-(2-Naphthylmethyl)cyclohexanone (1) and 2-(1-naphthyl-
methyl)cyclohexanone (4) were synthesized by reaction of
2-bromomethylnaphthalene and 1-bromomethylnaphtha-
lene, respectively, with 1-pyrrolidino-1-cyclohexene by
the published method.7 9-Bromomethylphenanthrene was
synthesized from 9-methylphenanthrene by bromination
with N-bromosuccinimide in CCl4 in the presence of
benzoyl peroxide.7 2-Phenoxyphenol (15b) was prepared
by the published method.13 1-Pyrrolidino-1-cyclohexene,
2-benzylphenol (9a), 2-hydroxybiphenyl (10a), and
m-chloroperbenzoic acid (m-CPBA) were purchased from
the Aldrich Chemical Co. (CAUTION: m-CPBA is poten-
tially explosive when dry). 1-Pyrrolidino-1-cyclohexene
and tri¯uoromethanesulfonic anhydride (Tf2O) were puri-
®ed by distillation. Dimethylformamide (DMF), dimethyl-
acetamide (DMA), and 2,6-lutidine were dried over CaH2
prior to use. 1,4-Dioxane and triglyme were freshly distilled
from sodium/benzophenone ketal.
2.1.3. 2-(2-Naphthylmethyl)phenol tri¯ate (2b). To a
solution of 2a (1.00 g, 4.3 mmol) and 2,6-lutidine
(0.80 mL, 6.9 mmol) in dry CH2Cl2 (30 mL) was added
tri¯ic anhydride (0.90 mL, 5.4 mmol) in CH2Cl2 (20 mL)
over 1 h under argon at 2308C. The cooling bath was
changed to ice, and stirring was continued for an additional
hour. Reaction was quenched by addition of water (50 mL),
and the solution was allowed to warm to room temperature.
Conventional workup followed by chromatography on a
silica gel column eluted with EtOAc±hexane (1:15) gave
2b (1.56 g, 100%) as a white solid, mp 50±518C: 1H NMR
(CDCl3) d 7.76±7.85 (m, 3), 7.65 (s, 1), 7.43±7.50 (m, 2),
7.18±7.34 (m, 5), 4.27 (s, 2, CH2); 13C NMR (CDCl3) d
147.9, 135.9, 133.9, 133.5, 132.2, 131.9, 128.4, 128.2,
127.7, 127.6, 127.3, 126.2, 125.7, 121.4, 118.6 (q, CF3,
Jˆ320.0 Hz), 35.8; 19F NMR (CDCl3) d 273.50; FAB
MS m/z 366 (M1). Anal. Calcd for C18H13F3O3S: C,
59.01; H, 3.58. Found: C, 59.02; H, 3.64.
NMR spectra were recorded on a 400 MHz spectrometer
in CDCl3 with tetramethylsilane as an internal standard.
Integrations were consistent with all structural assignments.
Mass spectra (MS) and HRMS were performed by the
University of Illinois at Urbana-Champaign, School of
Chemical Sciences. Microanalyses were conducted by
Atlantic Microlab, Inc. Melting points are uncorrected.
2.1.4. 2-(1-Naphthylmethyl)phenol (7a). Dehydrogenation
of 4 (3.07 g, 12.9 mmol) by the procedure employed for
analogous reaction of 1 gave 7a (2.43 g, 81%) as an oil:
1H NMR (CDCl3) d 8.02±8.97 (m, 1), 7.84±7.90 (m, 1),

5930
J.-Q. Wang, R. G. Harvey / Tetrahedron 58 (2002) 5927±5931
7.76 (d, 1, Jˆ8.26 Hz), 7.45±7.50 (m, 2), 7.37±7.42 (m, 1),
7.22±7.26 (m, 1), 7.10±7.16 (m, 1), 6.95±7.00 (m, 1), 6.80±
6.86 (m, 2), 4.82 (br s, 1, OH), 4.44 (s, 2, CH2); 13C NMR
(CDCl3) d 153.5, 135.4, 133.9, 132.1, 130.8, 128.7, 127.7,
127.3, 126.5, 126.2, 126.1, 125.7, 125.6, 124.0, 121.0,
115.5, 33.0.
273.91; FAB MS m/z 302 (M1). Anal. Calcd for
C13H9F3O3S: C, 51.66; H, 3.00. Found: C, 51.74; H, 3.04.
2.1.10. 7H-Benzo[c]xanthene (3). A solution of 2b (1.00 g,
2.7 mmol), Pd(PPh3)2Cl2 (192 mg, 0.27 mmol), LiCl (347
mg, 8.2 mmol), and DBU (0.5 mL, 3.3 mmol) in dry DMF
(30 mL), was heated at 1458C under argon for 18 h. After
cooling, the dark brown solution was transferred to a sepa-
ratory funnel. Water and ether were added. The ether layer
was washed 3 times with water, dried over MgSO4, and
evaporated to dryness. The residue was chromatographed
on a column of silica gel eluted with hexane to yield 3
(210 mg, 33%) as a white solid, mp 88±898C (lit12 90±
2.1.5. 2-(1-Naphthylmethyl)phenol tri¯ate (7b). Conver-
sion of 7a (2.37 g, 10 mmol) to a tri¯ate ester by the method
employed for 2b gave 7b (3.42 g, 92%) as an oil: 1H NMR
(CDCl3) d 7.86±7.91 (m, 1), 7.80±7.85 (m, 2), 7.42±7.51
(m, 3), 7.24±7.37 (m, 3), 7.11±7.17 (m, 1), 6.86±6.91 (m,
1), 4.54 (s, 2, CH2); 13C NMR (CDCl3) d 147.8, 134.0,
133.9, 133.6, 132.0, 131.2, 128.8, 128.4, 128.1, 127.9,
127.8, 126.3, 125.8, 125.5, 123.9, 121.2, 118.6 (q, CF3,
Jˆ319.55 Hz), 32.78; 19F NMR (CDCl3) d 273.42; FAB
HRMS Calcd for C18H13F3O3S: m/z 366.0538; Found:
366.0537. Anal. Calcd for C18H13F3O3S: C, 59.01; H,
3.58. Found: C, 59.29; H, 3.60.
1
918C): H NMR (CDCl3) d 8.40 (d, 1, Jˆ8.20 Hz), 7.80
(d, 1, Jˆ7.95 Hz), 7.45±7.60 (m, 3), 7.20±7.29 (m, 4),
7.04±7.12 (m, 1), 4.19 (s, 2, CH2); 13C NMR (CDCl3) d
151.7, 146.3, 133.3, 129.0, 127.6, 127.5, 126.6, 125.9,
125.8, 124.2, 123.2, 122.3, 121.4, 120.3, 116.6, 114.1,
28.0; FAB MS m/z 232 (M1). Anal. Calcd for C17H12O:
C, 87.90; H, 5.21. Found: C, 88.03; H, 5.18.
2.1.6. 2-(9-Phenanthrylmethyl)phenol (8a). Catalytic
dehydrogenation of 5 (2.00 g, 6.9 mmol) by the procedure
employed for reaction of 1 gave 8a (1.50 g, 76%) as a white
2.1.11. 12H-Benzo[a]xanthene (11). Analogous reaction of
7b (3.35 g, 9.1 mmol) gave 11 (470 mg, 22%) as a white
1
1
solid, mp 165±1668C: H NMR (CDCl3) d 8.75 (d, 1, Jˆ
solid, mp 89±908C (lit15 808C): H NMR (CDCl3) d 7.86
8.43 Hz), 8.68 (d, 1, Jˆ8.48 Hz), 8.10 (d, 1, Jˆ8.44 Hz),
7.79 (d, 1, Jˆ8.07 Hz), 7.54±7.70 (m, 4), 7.50 (s, 1), 7.14±
7.20 (m, 1), 7.02±7.07 (m, 1), 6.83±6.90 (m, 2), 4.91 (br s,
1, OH), 4.47 (s, 2, CH2); 13C NMR (CDCl3) d 153.5, 133.7,
131.7, 131.3, 130.8, 130.7, 129.9, 128.3, 127.7, 127.1,
126.7, 126.6, 126.4, 126.3, 125.9, 124.7, 123.1, 122.4,
121.1, 115.5; FAB MS m/z 284 (M1). Anal. Calcd for
C21H16O: C, 88.70; H, 5.67. Found: C, 88.48; H, 5.63.
(d, 1, Jˆ8.44 Hz), 7.82 (d, 1, Jˆ8.11 Hz), 7.72 (d, 1, Jˆ
8.93 Hz), 7.54±7.59 (m, 1), 7.40±7.45 (m, 1), 7.29±7.32
(m, 1), 7.20±7.27 (m, 2), 7.05±7.10 (m, 2), 4.37 (s, 2,
CH2); 13C NMR (CDCl3) d 151.0, 148.6, 132.0, 130.1,
129.4, 128.5, 128.3, 127.7, 126.7, 124.1, 123.1, 122.2,
119.5, 117.9, 116.5, 111.6, 24.8; FAB MS m/z 232 (M1).
Anal. Calcd for C17H12O: C, 87.90; H, 5.21. Found: C,
87.81; H, 5.34.
2.1.7. 2-(9-Phenanthrylmethyl)phenol tri¯ate (8b). Con-
version of 8a (1.00 g, 3.52 mmol) to its tri¯ate ester by the
method employed for 2b gave 8b (1.42 g, 97%) as a viscous
oil: 1H NMR (CDCl3) d 8.75 (d, 1, Jˆ8.44 Hz), 8.69 (d, 1,
Jˆ8.24 Hz), 7.81±7.90 (m, 2), 7.53±7.70 (m,5), 7.38 (d, 1,
Jˆ8.18 Hz), 7.26±7.32 (m, 1), 7.10±7.16 (m, 1), 6.97 (d, 1,
Jˆ7.70 Hz), 4.57 (s, 2, CH2); 13C NMR (CDCl3) d 147.8,
133.3, 132.1, 131.6, 131.2, 130.9, 130.8, 130.1, 128.7,
128.4, 128.3, 128.2, 126.9, 126.8, 126.6, 126.5, 124.7,
123.2, 122.5, 121.3, 118.7 (q, CF3, Jˆ320.60 Hz), 33.35;
19F NMR (CDCl3) d 273.37; FAB HRMS Calcd for
C22H15F3O3S: m/z 416.0694; Found: 416.0695. Anal.
Calcd for C22H15F3O3S: C, 63.46; H, 3.63. Found: C,
63.31; H, 3.76.
2.1.12. 14H-Dibenzo[a,c]xanthene (12). Analogous reac-
tion of 8b (1.24 g, 3.0 mmol) gave 12 (480 mg, 57%) as a
white solid, mp 186±1888C: 1H NMR (CDCl3) d 8.61±8.67
(m, 2), 8.46±8.50 (m, 1), 7.84±7.87 (m, 1), 7.55±7.70 (m,
4), 7.22±7.34 (m, 3), 7.08±7.13 (m,1), 4.32 (s, 2, CH2); 13
C
NMR (CDCl3) d 150.7, 144.0, 131.0, 130.4, 129.4, 127.3,
127.1, 126.81, 126.7, 124.7, 123.3, 122.8, 122.7, 122.4,
122.2, 119.5, 116.5, 107.9, 25.0; FAB MS m/z 282 (M1).
Anal. Calcd for C21H14O: C, 89.34; H, 5.00. Found: C,
89.26; H, 5.10.
2.1.13. 2-(2-Naphthoxy)phenol (14b). To a solution of
2-naphthol (5.48 g, 38 mmol) and 2-¯uorobenzaldehyde
(4.0 mL, 38 mmol) in dry DMA (40 mL) was added
anhydrous K2CO3. The mixture was heated at re¯ux for
2 h, then allowed to cool. EtOAc was added, and the solu-
tion was washed with water and brine. The organic layer
was dried over MgSO4, and evaporated to dryness. The
residue was chromatographed on a silica gel column.
Elution with hexane±CH2Cl2 provided 2-(2-naphthoxy)-
2.1.8. 2-Benzylphenol tri¯ate (9b). Analogous conversion
of 2-benzylphenol (2.12 g, 11.5 mmol) to its tri¯ate ester
gave 9b (3.51 g, 97%) as an oil: 1H NMR (CDCl3) d
7.20±7.40 (m, 9), 4.13 (s, 2, CH2); 13C NMR (CDCl3) d
147.9, 138.4, 134.0, 131.8, 129.1, 128.6, 128.4, 128.2,
126.6, 121.3, 118.6 (q, CF3, Jˆ319.40 Hz), 35.72; 19F
NMR (CDCl3) d 273.58; Anal. Calcd for C14H11F3O3S:
C, 53.16; H, 3.51. Found: C, 53.26; H, 3.55.
1
benzaldehyde (13) (7.94 g, 84%) as a pale yellow oil: H
NMR (CDCl3) d 10.56 (s, 1, CHO), 7.98 (d, 1, Jˆ9.7 Hz),
7.84±7.89 (m, 2), 7.71 (m, 1), 7.45±7.51 (m, 3), 7.37 (s, 1),
7.28±7.31 (m, 1), 7.21 (m, 1), 6.94 (d, 1, Jˆ10.3 Hz). Anal.
Calcd for C17H12O2: C, 82.24; H, 4.87. Found: C, 82.12; H,
5.94.
2.1.9. 2-Hydroxybiphenyl tri¯ate (10b). Analogous
conversion of 2-hydroxybiphenyl (1.95 g, 11.5 mmol) to
1
its tri¯ate ester gave 10b (3.20 g, 93%) as an oil: H NMR
(CDCl3) d 7.40±7.53 (m, 9); 13C NMR (CDCl3) d 146.8,
135.5, 135.5, 131.9, 129.3, 129.0, 128.5, 128.5, 128.3,
122.1, 118.3 (q, CF3, Jˆ320.80 Hz); 19F NMR (CDCl3) d
To a solution of 13 (5.43 g, 22 mmol) in CHCl3 (80 mL) was
added m-CPBA (9.50 g). The solution was stirred at 308C
for 6 h then washed with dilute NaHSO3, saturated NaHCO3

J.-Q. Wang, R. G. Harvey / Tetrahedron 58 (2002) 5927±5931
5931
(3X), and water. Evaporation of the solvent afforded crude
References
2-(2-naphthoxy)phenol formate (14a) as an oil. This
compound was dissolved MeOH (100 mL), 2 drops of
conc. HCl were added, and the solution was stirred at
room temperature for 1 h. Reaction was quenched by
addition of NaCO3 (2 g), and the solution was ®ltered and
evaporated to dryness. Chromatography of the residue on a
silica gel column eluted with hexane±CH2Cl2 (2:1) afforded
2-(2-naphthoxy)phenol (14b) (2.73 g, 53%) as a white solid,
mp 106±1078C: 1H NMR (CDCl3) d 7.82 (t, 2, Jˆ8.00 Hz),
7.69 (d, 1, Jˆ8.50 Hz), 7.38±7.47 (m, 2), 7.23±7.30 (m, 2),
7.05±7.10 (m, 2), 6.94 (d, 1, Jˆ8.50 Hz), 6.83±6.88 (m, 1),
5.62 (br s, 2, OH); 13C NMR (CDCl3) d 154.5, 147.5, 143.4,
134.2, 130.3, 130.1, 127.8, 127.2, 126.7, 125.0, 124.9,
120.7, 119.1, 119.1, 116.3, 113.2; FAB MS m/z 236 (M1).
Anal. Calcd for C16H12O2: C, 81.34; H, 5.12. Found: C,
81.24; H, 5.10.
1. Weyand, E. H.; Chen, Y.-C.; Wu, Y.; Koganti, A.; Dunsford,
H. A.; Rodriguez, L. V. Chem. Res. Toxicol. 1995, 8, 949.
2. Weyand, E. H.; Wu, Y. Chem. Res. Toxicol. 1995, 8, 955.
Culp, S. J.; Warbritton, A. R.; Smith, B. A.; Li, E. E.; Beland,
F. A. Carcinogenesis 2000, 21, 1433.
3. Koganti, A.; Singh, R.; Rozett, K.; Modi, N.; Goldstein, L. S.;
Roy, T. A.; Zhang, F.-J.; Harvey, R. G.; Weyand, E. H.
Carcinogenesis 2000, 21, 1601.
4. International Agency for Research on Cancer. Polynuclear
Aromatic Compounds, Part 1, Chemical, Environmental,
and ExperimentalData ; Monographs on the Evaluation of
the Carcinogenic Risk of Chemicals to Humans, Vol. 32;
IARC: Lyon, France, 1983; p 189.
5. The principal mechanism of carcinogenesis by polycyclic
aromatic hydrocarbons involves activation by microsomal
enzymes to bay or fjord region diol epoxide metabolites that
bind to DNA, resulting in mutations that lead to tumor
induction. Reviews: Harvey, R. G. Polycyclic Aromatic
Hydrocarbons: Chemistry and Carcinogenesis; Cambridge
University: Cambridge, UK, 1991. Harvey, R. G.; Geacintov,
N. E. Acc. Chem. Res. 1988, 21, 66.
2.1.14. 2-(2-Naphthoxy)phenol tri¯ate (14c). Conversion
of 14b (1.00 g, 4.2 mmol) to its tri¯ate ester by the usual
method gave 14c (1.55 g, 100%) as a white solid, mp 528C:
1H NMR (CDCl3) d 7.82±7.92 (m, 2), 7.74 (d, 1, Jˆ
7.80 Hz), 6.97±7.52 (m, 8); 13C NMR (CDCl3) d 153.1,
149.4, 140.0, 134.1, 130.8, 130.3, 129.3, 127.8, 127.3,
126.8, 125.3, 123.7, 123.1, 119.7, 119.5, 118.7 (q, CF3, Jˆ
319.75 Hz); 19F NMR (CDCl3) d 273.36. Anal. Calcd for
C17H11F3O4S: C, 55.44; H, 3.01. Found: C, 55.54; H, 2.99.
6. 3-Methoxybenzo[c]¯uorene is a potential synthetic precursor
of the anti- and syn-diol epoxides of BcF, suspected to be the
ultimate carcinogenic metabolites of BcF. Wang, J.-Q.;
Weyand, E. H.; Harvey, R. G. J. Org. Chem., in press.
7. Harvey, R. G.; Pataki, J.; Cortez, C.; Di Raddo, P.; Yang, C. X.
J. Org. Chem. 1991, 56, 1210.
2.1.15. 2-Phenoxyphenol tri¯ate (15c). Conversion of
2-phenoxyphenol (15b) (2.14 g, 11.5 mmol) to its tri¯ate
ester by the usual method gave 15c (3.41 g, 93%) as an
8. Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Wiley±
VCH: New York, 1997.
1
oil: H NMR (CDCl3) d 7.35±7.44 (m, 3), 7.26±7.31 (m,
9. Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 977.
1), 7.20±7.25 (m, 1), 7.11±7.16 (m, 3), 6.98 (dd, 1, Jˆ
1.50 Hz); 13C NMR (CDCl3) d 155.4, 149.5, 140.0, 130.0,
129.2, 124.6, 123.4, 122.9, 119.4, 119.1, 118.8 (q, CF3,
Jˆ320.50 Hz); 19F NMR (CDCl3) d 273.54; FAB MS
m/z 318 (M1). Anal. Calcd for C13H9F3O4S: C, 49.06; H,
2.85. Found: C, 49.03; H, 2.74.
10. Aryl tri¯ates are widely used as substrates in cross-coupling
reactions of alkenes (Heck reaction) and alkynes: Ritter, K.
Synthesis 1993, 735±762. Hayashi, T.; Kubo, A.; Ozawa, F.
Pure Appl. Chem. 1992, 64, 421. Dushin, R. G.; Danishefsky,
S. J. Am. Chem. Soc. 1992, 110, 3296.
11. Rice, J. E.; Cai, Z. W. J. Org. Chem. 1993, 58, 1415.
12. Baddar, F. G.; Gindy, M. J. Chem. Soc. 1951, 64.
13. Yeager, G. W.; Schissel, D. N. Synthesis 1995, 28.
14. Tsuji, J. Palladium Reagents and Catalysis; Wiley: New
York, 1995; pp 87±97. Sargent, M. V.; Stransky, P. O.
J. Chem. Soc., Perkin Trans. 1 1982, 1605. De Lombaert,
S.; Blanchard, L.; Stamford, L. B.; Tan, J.; Wallace, E. M.;
Satoh, Y.; Fitt, J.; Hoyer, D.; Simonsbergen, D.; Moliterni, J.;
Marcopoulos, N.; Savage, P.; Chou, M.; Trapani, A. J.; Jeng,
A. Y. J. Med. Chem. 2000, 43, 488.
2.1.16. Dibenzofuran (17). Palladium-catalyzed reaction of
14c (2.73 g, 8.6 mmol) by the procedure employed for the
preparation of 7H-benzo[c]xanthene (3) furnished 17
(1.38 g, 96%) as a white solid, mp 81±828C (lit16 838C):
1H NMR (CDCl3) d 7.99 (d, 2, Jˆ7.69 Hz); 7.64 (d, 2,
Jˆ8.17 Hz); 7.99 (t, 2, Jˆ7.39 Hz); 7.99 (t, 2, Jˆ
1
7.54 Hz); the H NMR spectrum of 17 matched that of a
commercial sample.17
2.1.17. Benzo[b]naphtho[2,3-d]furan (16). Analogous
reaction of 14c (1.22 g, 3.3 mmol) by the same procedure
gave 17 (580 mg, 80%) as a white solid, mp 202±2048C
(lit18 207.5±2098C): 1H NMR (CDCl3) d 8.39 (s, 1),
7.99±8.12 (m, 2), 7.96 (d, 1, Jˆ7.55 Hz), 7.91 (s, 1),
7.43±7.62 (m, 4), 7.32±7.42 (m, 1); 13C NMR (CDCl3) d
157.6, 154.8, 133.0, 130.1, 128.3, 127.7, 125.8, 125.4,
124.3, 123.9, 122.7, 121.3, 119.2, 111.5, 106.9. Anal. Calcd
for C16H10O: C, 88.05; H, 4.62. Found: C, 88.14; H, 4.62.
15. Knapp, W. J. Prakt. Chem. 1936, 146 (ii), 113.
16. Williams, A. F. Nature 1948, 162, 925.
17. Aldrich Library of 13C and 1H FT NMR Spectra; Vol. 3,
Spectrum #171, 1993.
18. Markgraf, J. H.; Patterson, D. E. J. Hetercycl. Chem. 1996, 33,
109.
Acknowledgements
This research was supported by contract EP-P2394/C1070
from the Electric Power Research Institute, Palo Alto, CA.