Rearrangements of the Diels-Alder cycloadducts obtained from acetylenic sulfones and 1,3-diphenylisobenzofuran

Article abstract of DOI:10.1021/jo060598e

1,3-Diphenylisobenzofuran afforded Diels-Alder cycloadducts 4a,b with n-butyl- and phenyl-substituted acetylenic sulfones 3a,b, respectively. The products underwent various types of rearrangements under pyrolytic, acid-catalyzed, and photochemical conditi

Full text of DOI:10.1021/jo060598e

Rearrangements of the Diels-Alder Cycloadducts Obtained from
Acetylenic Sulfones and 1,3-Diphenylisobenzofuran
Thomas G. Back,* Masood Parvez, and Huimin Zhai
Department of Chemistry, UniVersity of Calgary, Calgary, Alberta, Canada, T2N 1N4
tgback@ucalgary.ca
ReceiVed March 18, 2006
1,3-Diphenylisobenzofuran afforded Diels-Alder cycloadducts 4a,b with n-butyl- and phenyl-substituted
acetylenic sulfones 3a,b, respectively. The products underwent various types of rearrangements under
pyrolytic, acid-catalyzed, and photochemical conditions. In the presence of acid, or upon heating in xylenes,
they afforded the ketones 5a,b. In addition, the dehydration product 7a was produced from the pyrolysis
of 4a, and the unexpected transposed ketone 6b was generated under acid-catalyzed or pyrolytic conditions
from 4b via a postulated epoxide intermediate. The photolysis of 4a afforded ketone 5a as the sole
isolated product, whereas 5b afforded oxepin 8b and indenyl phenyl ketone 9b. The formation of the
latter two products can be rationalized by a series of pericyclic reactions. These include an intramolecular
[2+2] cycloaddition, followed by a 1,3-dipolar cycloreversion, for the transformation of 4b to 8b and a
series of electrocyclic and [1,3]sigmatropic reactions to convert 8b into 9b.
1,3-Diphenylisobenzofuran (1) is a highly reactive diene that
readily undergoes Diels-Alder cycloadditions with a wide range
of dienophiles.1-4 It has most notably served as a reagent for
the preparation of various classes of polycyclic aromatic
compounds, as well as for trapping unstable dienophiles. The
aromatization of the benzene ring during cycloadditions provides
a strong driving force for such processes.
Earlier studies have shown that a variety of further reactions
of the Diels-Alder products obtained from 1 and various
alkenes or acetylenes are possible under the conditions of the
cycloadditions, upon subsequent workup, or upon treatment
under acidic conditions. When an acetylene is employed as the
dienophile, the resulting cycloadduct is an oxabenzonorborna-
diene derivative 2 (Scheme 1), which lends itself readily to a
variety of further transformations. These include hydrogenation
and dehydration5a or deoxygenation3,5c,6 to afford naphthalene
derivatives, as well as spontaneous rearrangements to ketones,7or
transformations that are promoted by acids,5 silica gel,8 or by
the presence of a bridgehead alkylthio substituent.9 The conver-
sion of the initial cycloadducts derived from cyclopropenes and
1 to ketones or epoxides by oxygen via free radical reactions
has also been reported.10
* Corresponding author. Tel.: (403) 220-6256. Fax: (403) 289-9488.
(1) Kierkus, P. C. In Encyclopedia of Reagents for Organic Synthesis;
Paquette, L. A., Ed.; Wiley: Chichester, 1995; Vol. 4, pp 2223-2225.
(2) For reviews of the reactions, synthesis, and applications of benzo-
furans, including isobenzofurans, see: (a) Heaney, H.; Ahn, J. S. In
ComprehensiVe Heterocyclic Chemistry II; Bird, C. W., Ed.; Elsevier:
Oxford, 1996; Chapter 2.06, pp 297-350. (b) Friedrichsen, W. In
ComprehensiVe Heterocyclic Chemistry II; Bird, C. W., Ed.; Elsevier:
Oxford, 1996; Chapter 2.07, pp 351-393. (c) Keay, B. A.; Dibble, P. W.
In ComprehensiVe Heterocyclic Chemistry II; Bird, C. W., Ed.; Elsevier:
Oxford, 1996; Chapter 2.08, pp 395-436.
(5) (a) Wittig, G.; Krebs, A. Chem. Ber. 1961, 94, 3260. (b) Wittig, G.;
Pohlke, R. Chem. Ber. 1961, 94, 3276. (c) Wittig, G.; Weinlich, J.; Wilson,
E. R. Chem. Ber. 1965, 98, 458. (d) Wittig, G.; Mayer, U. Chem. Ber.
1963, 96, 329.
(6) Feldman, K. S.; Ruckle, R. E., Jr.; Ensel, S. M.; Weinreb, P. H.
Tetrahedron Lett. 1992, 33, 7101.
(7) Kitamura, T.; Kotani, M.; Yokoyama, T.; Fujiwara, Y. J. Org. Chem.
1999, 64, 680.
(8) (a) Komatsu, K.; Aonuma, S.; Jinbu, Y.; Tsuji, R.; Hirosawa, C.;
Takeuchi, K. J. Org. Chem. 1991, 56, 195.
(9) Cochran, J. E.; Padwa, A. Tetrahedron Lett. 1995, 36, 3495.
(10) Lee, G.-A.; Huang, A. N.; Chen, C.-S.; Li, Y. C.; Jann, Y.-C. J.
Org. Chem. 1997, 62, 3355.
(3) Rodrigo, R. Tetrahedron 1988, 44, 2093.
(4) Friedrichsen, W. AdV. Heterocycl. Chem. 1980, 26, 135.
10.1021/jo060598e CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/16/2006
5254
J. Org. Chem. 2006, 71, 5254-5259

Rearrangements of Diels-Alder Cycloadducts
SCHEME 1
SCHEME 3
SCHEME 2
ketone 5a and the alkenyl naphthalene 7a in roughly equal
amounts. The similar treatment of the cycloadduct 4b, obtained
from 1 and the phenyl-substituted acetylenic sulfone 3b,
produced 5b (analogous to 5a) along with the transposed ketone
6b in the ratio of about 1:2. Under acid-catalyzed conditions,
the reactions of 4a and 4b proceeded smoothly at room
temperature. Thus, 5a was the exclusive product from 4a, while
4b afforded a mixture of 5b and 6b similar to that obtained
earlier under neutral conditions and elevated temperature.
Finally, photolysis of the cycloadducts 4a and 4b in dichloro-
methane at 300 nm produced ketone 5a as the only isolable
product in the n-butyl series, while the corresponding analogue
5b was completely absent in the phenyl series. Instead, 4b
afforded the benzoxepin 8b and the indenyl phenyl ketone 9b
as the major and minor products. The structures of 4a, 5a, 5b,
6b, and 8b were established unequivocally by X-ray crystal-
lography, while those of 4b, 7a, and 9b were deduced from
spectroscopic data (see Experimental Section and Supporting
Information).
A plausible mechanism for the rearrangement of 4a,b to 5a,b
under acid-catalyzed conditions is shown in Scheme 3. The
formation of carbocations 10a,b, followed by a 1,2-shift of the
phenyl substituent via the phenonium ions 11a,b, would account
for the formation of 5a,b. This resembles the acid-catalyzed
rearrangements of cycloadducts 2 [where R, R′ ) -(CH2)n-],
which were reported previously by Wittig and co-workers.5c,d
The formation of 6b from 4b under similar conditions is more
noteworthy, because it requires the formal 1,2-transposition of
the bridging oxygen atom with that of the phenyl group. This
can be rationalized by invoking an epoxide intermediate 12,
which can either regenerate 10 or produce the rearranged
carbocation 13. 1,2-Phenyl migration in 13b leads to the
observed isomeric ketone 6b. Although the epoxides 12a,b could
not be isolated, their intermediacy in Scheme 3 is supported by
the observation that 14a, obtained by hydrogenation of 7a,
afforded the same rearranged ketone 5a when treated with
MCPBA, under conditions which are expected to produce the
same epoxide 12a (Scheme 4).14 The formation of the transposed
Among the acetylenic dienophiles that have been investigated
to date, three fluorinated acetylenic sulfones underwent Diels-
Alder reactions with 1, affording the corresponding stable,
isolable cycloadducts 2 [R ) n-C4F9SO2; R′ ) Ph or n-Pr11
and R ) CF3SO2; R′ ) 1-(8-iodonaphthyl)6]. Our ongoing
interest in acetylenic sulfones12,13 prompted us to investigate
the cycloadditions of two representative nonfluorinated deriva-
tives with 1. We now report the results of these cycloadditions,
along with a series of remarkable rearrangements of the resulting
products.
Results and Discussion
The cycloaddition of 1 with acetylenic sulfones 3a and 3b
proceeded smoothly upon heating in toluene to afford the
expected products 4a and 4b in high yield. The latter were then
subjected to further transformations under pyrolytic, acid-
catalyzed, and photolytic conditions. The results are summarized
in Scheme 2. Thus, when heated for 60 h in xylenes at 150 °C,
the butyl-substituted cycloadduct 4a afforded the rearranged
(11) (a) Hanack, M.; Massa, F. Tetrahedron Lett. 1977, 661. (b) Massa,
F.; Hanack, M.; Subramanian, L. R. J. Fluorine Chem. 1982, 19, 601.
(12) For a review of acetylenic and allenic sulfones, see: Back, T. G.
Tetrahedron 2001, 57, 5263.
(13) For recent examples, see: (a) Back, T. G.; Hamilton, M. D.; Lim,
V. J. J.; Parvez, M. J. Org. Chem. 2005, 70, 967. (b) Back, T. G.; Parvez,
M.; Wulff, J. E. J. Org. Chem. 2003, 68, 2223. (c) Back, T. G.; Nakajima,
K. J. Org. Chem. 2000, 65, 4543. (d) Back, T. G.; Nakajima, K. J. Org.
Chem. 1998, 63, 6566.
(14) For the oxidation of other polycyclic arenes with peracids, see:
Lewis, S. N. In Oxidation; Augustine, R. L., Ed.; Dekker: New York, 1969;
Vol. 1, pp 235-236.
J. Org. Chem, Vol. 71, No. 14, 2006 5255

Back et al.
SCHEME 4
SCHEME 5
SCHEME 6
ketone 6b in the phenyl series, but not of 5b in the butyl series,
can be attributed to the generally more facile migration of the
phenyl group in cation 13b compared to that of an n-butyl group
in cation 13a.15
The absence of any noticeable amounts of the regioisomeric
products of 5a,b and 6b, which would result from the acid-
catalyzed cleavage of the other C-O bond in 4a,b, is notewor-
thy. This is attributed to the greater expected stability resulting
from the cross-conjugation of the delocalized cation with the
sulfone moiety in 10a,b, compared to the linear conjugation in
the regioisomeric species 15a,b, because the electron-withdraw-
ing sulfone group is expected to destabilize the respective
cations. Similarly, 16a,b is expected to be destabilized relative
to 11a,b by the proximity of the sulfone moiety.16
of either 0.2 or 2.0 mol of the radical inhibitor 2,6-di-tert-butyl-
4-cresol (butylated hydroxytoluene, BHT) did not suppress the
formation of the above products. This suggests that 4a and 4b
undergo heterolytic C-O bond cleavage to produce dipolar,
rather than diradical, intermediates in the pyrolytic reaction.
The photolysis of the butyl derivative 4a afforded the same
ketone 5a that had been previously observed as the sole or major
product under acid-catalyzed or pyrolytic conditions, respec-
tively. In contrast to the pyrolytic conversion of 4a to 5a, the
photochemical formation of 5a was suppressed by the inclusion
of BHT, suggesting that, under these conditions, the photo-
chemical process does proceed via a radical pathway. However,
in the phenyl series, 4b produced no significant amounts of
either ketone 5b or 6b. Instead, the benzoxepin 8b and exocyclic
ketone 9b were obtained. Earlier photochemical experiments
on 7-oxanorbornadienes revealed that such systems undergo
formal intramolecular photochemical [2+2] cycloadditions to
the corresponding oxaquadricyclanes, followed by thermal
isomerization to oxepins via carbonyl ylides.17 A similar process
is shown in Scheme 6, where the photoisomerization of 4b via
oxaquadricyclane 18b and ylide 19b affords the observed
product 8b.
The reactions in Scheme 2 that were performed under neutral
pyrolytic conditions resemble the acid-catalyzed process in the
case of the phenyl series, affording comparable amounts of the
principal products 5b and 6b from 4b. On the other hand, 4a
in the butyl series produced a new product 7a, along with a
comparable amount of the previously observed 5a. The forma-
tion of 7a can be rationalized by the elimination and ring-
opening of the oxygen bridge in 4a to generate 17a, followed
by elimination of water and aromatization (Scheme 5). Inclusion
(15) For lead references and a discussion of the migratory aptitudes of
various types of substituents, see: Smith, M. B.; March, J. March’s
AdVanced Organic Chemistry: Reactions, Mechanisms and Structure, 5th
ed.; Wiley: New York, 2001; pp 1384-1386.
(16) On the other hand, preliminary molecular modeling performed by
subjecting 10a,b, 11a,b, 15a,b, and 16a,b to MMFF conformation searches
and PM3 geometry optimizations, followed by 3-21G* ab initio single-
point energy calculations (Spartan 2004 for Windows platform; Wave
function, Inc.), suggests that 15a,b and 16a,b are stabilized relative to 10a,b
and 11a,b, respectively, by intramolecular hydrogen bonding between their
hydroxyl groups and one of their sulfone oxygen atoms. Higher level
computations will be required to establish more precisely the relative roles
of resonance, inductive, and hydrogen-bonding effects in determining the
regioselectivity of these processes.
Moreover, control experiments revealed that photolysis of
pure benzoxepin 8b under similar conditions resulted in its
conversion to ketone 9b, whereas this transformation failed in
the dark. This indicates that 9b is produced from the further
(17) (a) Prinzbach, H.; Argue¨lles, M.; Druckrey, E. Angew. Chem., Int.
Ed. Engl. 1966, 5, 1039. (b) Vogel, P.; Willhalm, B.; Prinzbach, H. HelV.
Chim. Acta 1969, 52, 584. (c) Tochtermann, W.; Olsson, G. Chem. ReV.
1989, 89, 1203. (d) Tochtermann, W.; Timm, H.; Diekmann, J. Tetrahedron
Lett. 1977, 4311. (e) Tochtermann, W.; Ko¨hn, H. Chem. Ber. 1980, 113,
3249.
5256 J. Org. Chem., Vol. 71, No. 14, 2006

Rearrangements of Diels-Alder Cycloadducts
SCHEME 7
pentadienecarbaldehydes via a series of fused-ring dihydrofurans
and cyclopropanecarbaldehydes. Evidence for this pathway was
based on NMR detection of the intermediates. Formally, one
can envisage these transformations taking place by means of a
4π-electron electrocyclic ring closure, followed by a [1,3]sigma-
tropic rearrangement and a 4π-electron electrocyclic cyclo-
reversion to the cyclopentadienecarbaldehyde. A similar mech-
anism in the present case would proceed via intermediates 24b
and 25b and is shown in path C of Scheme 7.
We repeated the photoisomerization of 8b to 9b in the
presence of the radical inhibitor BHT but observed no significant
change in the rate or nature of the products of the reaction. While
this experiment does not unequivocally rule out the possibility
of radical intermediates, it is most consistent with path C, where
radical intermediates are not required. Furthermore, the photo-
chemical 6π-electron electrocyclic reaction required to convert
8b to epoxide 21b in path B would require a conrotatory ring
closure that would lead to a highly strained trans-epoxide. Path
B, therefore, appears unlikely if one assumes a concerted
mechanism for the formation of 21b. On the other hand, a
photochemical 4π-electron electrocyclic ring closure of 8b to
24b in path C would be disrotatory and would, therefore, lead
to the less-strained cis-fused dihydrofuran-cyclobutene system.
The subsequent sigmatropic rearrangement of 24b to 25b would
be expected to proceed with retention of configuration under
photochemical conditions to again afford a cis-fused cyclo-
propane moiety. Based on the above considerations and on
precedents with analogous systems, we tentatively favor the
Tochtermann mechanism shown in path C for the formation of
9b from 8b.21
The conversion of 8b to 9b was also highly regioselective,
and the isomer 26b was not observed. The reason for the
difference in behavior of 4a and 4b under photochemical
conditions is unclear at this time and requires further investiga-
tion.
photoisomerization of the benzoxepin 8b rather than via an
independent pathway from 4b or via a thermal process from
8b.
Several possible pathways for the transformation of 8b to
9b have at least partial precedent in the literature and are
summarized in Scheme 7. A diradical mechanism was suggested
as a possible pathway for the related photoisomerization of 4,5-
dihydrooxepin to 2-cyclopentenecarbaldehyde via homolytic
cleavage of a C-O bond, followed by radical recombination.18
This corresponds to path A in Scheme 7. Alternatively, the
photochemical interconversions of arene oxides with the cor-
responding oxepins have been extensively studied in polycyclic
aromatic hydrocarbon systems.19 Electrocyclic ring closures have
been proposed for these transformations.19a,d,e The analogous
process here would lead to epoxide 21b from 8b, which could
then undergo further rearrangement to 9b, possibly via diradicals
22b and 23b (path B in Scheme 7) or similarly by means of
dipolar intermediates. A third possibility is based on earlier work
by Tochtermann et al.20 who reported that the photolysis of
certain 3,6-alkanooxepins produced the corresponding cyclo-
In conclusion, the cycloaddition of 1,3-diphenylisobenzofuran
(1) with acetylenic sulfones 3a and 3b afforded the expected
Diels-Alder cycloadducts 4a and 4b. The further transforma-
tions of the latter products under acid-catalyzed and pyrolytic
conditions resulted in the regioselective formation of rearranged
ketones 5a and 5b, as well as the dehydration product 7a, from
the pyrolysis of 4a. The remarkable formation of ketone 6b
from 4b was rationalized by invoking an epoxide intermediate
that provides a pathway for the transposition of the oxygen
functionality. Although 4a again produced ketone 5a under
photochemical conditions, different products were observed from
4b. Thus, benzoxepin 8b was the initial product via a postulated
intramolecular [2+2] cycloaddition leading to an oxaquadri-
cyclane intermediate, followed by isomerization via a carbonyl
(18) Cockroft, R. D.; Waali, E. E.; Rhoads, S. J. Tetrahedron Lett. 1970,
3539.
(19) For example, see: (a) Balani, S. K.; Brannigan, I. N.; Boyd, D. R.;
Sharma, N. D.; Hempenstall, F.; Smith, A. J. Chem. Soc., Perkin Trans. 1
2001, 1091. (b) Agarwal, R.; Boyd, D. R. J. Chem. Soc., Perkin Trans. 1
1993, 2869. (c) Boyd, D. R.; Sharma, N. D.; Agarwal, S. K.; Gadaginamath,
G. S.; O’Kane, G. A.; Jennings, W. B.; Yagi, H.; Jerina, D. M. J. Chem.
Soc., Perkin Trans. 1 1993, 423. (d) Boyd, D. R.; Agarwal, S. K.; Balani,
S. K.; Dunlop, R.; Gadaginamath, G. S.; O’Kane, G. A.; Sharma, N. D.;
Jennings, W. B.; Yagi, H.; Jerina, D. M. J. Chem. Soc., Chem. Commun.
1987, 1633. (e) Shudo, K.; Okamoto, T. Chem. Pharm. Bull. 1973, 21,
2809. (f) Griffin, G. W.; Satra, S. K.; Brightwell, N. E.; Ishikawa, K.;
Bhacca, N. S. Tetrahedron Lett. 1976, 1239.
(20) (a) Heber, D.; Ro¨sner, P.; Tochtermann, W. Eur. J. Org. Chem.
2005, 4231. (b) Sczostak, A.; So¨nnichsen, F.; Tochtermann, W.; Peters,
E.-M.; Peters, K.; von Schnering, H. G. Tetrahedron Lett. 1985, 26, 5677.
(c) Tochtermann, W.; Olsson, G.; Sczostak, A.; So¨nnichsen, F.; Frauenrath,
H.; Runsink, J.; Peters, E.-M.; Peters, K.; von Schnering, H. G. Chem. Ber.
1989, 122, 199.
J. Org. Chem, Vol. 71, No. 14, 2006 5257

Back et al.
129.2, 128.9, 128.8, 128.39, 128.37, 128.2, 127.7, 127.3, 126.1,
125.7, 123.3, 122.3, 95.7, 95.4, 21.5; MS (m/z, %) 526 (M+, 0.2),
510 (0.7), 371 (100), 270 (78); HRMS calcd for C35H26O3S (M+),
526.1603; found, 526.1628. Anal. Calcd for C35H26O3S: C, 79.82;
H, 4.98. Found: C, 79.60; H, 4.98.
ylide. The exocyclic ketone 9b was produced by further
irradiation of 8b, rather than via an independent pathway from
4b. The transformation of 8b to 9b is consistent with a
mechanism involving successive pericyclic reactions: an elec-
trocyclic ring closure, a [1,3]sigmatropic rearrangement, and
an electrocyclic ring opening. These processes further illustrate
the rich and diverse behavior of 1 and its Diels-Alder
cycloadducts.
Pyrolysis of Cycloadduct 4a. A solution of 4a (342 mg, 0.676
mmol) in xylenes (4 mL) was heated in a sealed V-vial at 150 °C
for 60 h. The mixture was concentrated under reduced pressure to
afford a colorless oil that was separated by flash chromatography
(elution with 50% pentane-dichloromethane) to afford 149 mg
(45%) of 2-(trans-1-butenyl)-1,4-diphenyl-3-(p-toluenesulfonyl)-
naphthalene (7a) as a colorless oil: IR (film) 1595, 1440, 1321,
Experimental Section
Acetylenic sulfones 3a13c and 3b22 were prepared as descrbed
previously.
1
1150 cm-1; H NMR (300 MHz) δ 7.54-7.30 (m, 14H), 7.22-
7.14 (m, 2H), 7.12 (d, J ) 8.2 Hz, 2H), 6.42 (dt, J ) 16.1, 1.5 Hz,
1H), 4.93 (dt, J ) 16.1, 6.7 Hz, 1H), 2.36 (s, 3H), 1.80-1.68 (m,
2H), 0.56 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz) δ 142.8, 142.0,
141.1, 140.7, 139.9, 139.3, 137.7, 135.9, 134.34, 134.30, 132.5,
130.9, 130.3, 128.8, 128.31, 128.26, 128.0, 127.5, 127.4, 127.2,
126.92, 126.88, 126.34, 126.26, 26.2, 21.5, 12.6; MS (m/z, %) 488
(M+, 94), 381 (81), 302 (97), 119 (71), 105 (100); HRMS calcd
for C33H28O2S (M+), 488.1810; found, 488.1820.
Cycloaddition of 1,3-Diphenylisobenzofuran (1) with 1-(p-
Toluenesulfonyl)-1-hexyne (3a). A solution of 1 (567 mg, 2.10
mmol) and 3a (472 mg, 2.00 mmol) in toluene (4.5 mL) was heated
in a sealed V-vial at 109 °C for 1 d. The mixture was concentrated
under reduced pressure and separated by flash chromatography
(elution with 10% ethyl acetate-hexanes) to afford 806 mg (80%)
of the cycloadduct 4a as a light yellow oil. Crystallization from
ethyl acetate-hexanes gave white crystals: mp 159-164 °C; IR
(KBr) 1600, 1452, 1317, 1146 cm-1; 1H NMR (300 MHz) δ 7.88-
7.78 (m, 4H), 7.63-7.44 (m, 5H), 7.36-7.29 (m, 3H), 7.15-7.06
(m, 4H), 6.99 (d, J ) 8.2 Hz, 2H), 2.94 (ddd, J ) 12.3, 10.5, 5.3
Hz, 1H), 2.66 (ddd, J ) 12.0, 10.5, 4.3 Hz, 1H), 2.34 (s, 3H),
1.36-0.98 (m, 4H), 0.80 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz)
δ 171.8, 149.7, 148.2, 147.9, 143.4, 137.9, 134.0, 133.5, 129.0,
128.6, 128.5, 128.3, 128.1, 127.7, 127.2, 126.6, 125.9, 125.4, 121.4,
120.9, 93.4, 91.6, 30.1, 26.5, 22.7, 21.5, 13.6; MS (m/z, %) 506
(M+, 0.4), 350 (100), 270 (99), 105 (98), 77 (73); HRMS calcd for
C33H30O3S (M+), 506.1916; found, 506.1961. Anal. Calcd for
C33H30O3S: C, 78.23; H, 5.97. Found: C, 77.89; H, 5.76. The
structure was confirmed by X-ray crystallography (see Supporting
Information).
Further elution (50% pentane-dichloromethane) provided 164
mg (48%) of 2-n-butyl-2,4-diphenyl-3-(p-toluenesulfonyl)-2H-
naphthalen-1-one (5a) as a light yellow oil. Crystallization from
ethyl acetate-hexanes gave white crystals: mp 186-188 °C; IR
1
(KBr) 1677, 1594, 1447, 1315, 1301, 1137 cm-1; H NMR (300
MHz) δ 8.17-8.11 (m, 1H), 7.51-7.29 (m, 10H), 6.97 (td, J )
7.2 Hz, 1.6 Hz, 1H), 6.84 (d, J ) 8.2 Hz, 2H), 6.71-6.66 (m, 1H),
6.61 (d, J ) 8.2 Hz, 2H), 6.52 (d, J ) 7.7 Hz, 1H), 3.37 (td, J )
12.8 Hz, 4.1 Hz, 1H), 3.01 (td, J ) 12.8 Hz, 4.1 Hz, 1H), 2.30 (s,
3H), 1.92-1.75 (m, 1H), 1.58-1.42 (m, 2H), 1.19-1.04 (m, 1H),
0.96 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz) δ 198.4, 148.1, 144.2,
142.7, 141.1, 139.6, 137.9, 134.7, 134.1, 131.9, 130.6, 130.2, 129.2,
128.7, 128.6, 128.3, 128.1, 127.9, 127.8, 127.5, 127.4, 127.2, 126.8,
60.2, 36.3, 26.9, 23.2, 21.4, 13.9; MS (m/z, %) 506 (M+, 0.2), 449
(13), 351 (100), 307 (30), 295 (56), 265 (41), 219 (65), 91 (59);
HRMS calcd for C33H30O3S (M+), 506.1916; found, 506.1937. Anal.
Calcd for C33H30O3S: C, 78.23; H, 5.97. Found: C, 77.92; H, 5.96.
The structure was confirmed by X-ray crystallography (see Sup-
porting Information).
Further elution with 15% ethyl acetate-hexanes gave 49 mg
(5%) of 5a as a light yellow oil (vide infra).
Cycloaddition of 1,3-Diphenylisobenzofuran (1) with 1-Phen-
yl-2-(p-toluenesulfonyl)ethyne (3b). A solution of 1 (567 mg, 2.10
mmol) and 3b (512 mg, 2.00 mmol) in toluene (4.5 mL) was heated
in a sealed V-vial at 124 °C for 42 h. The reaction mixture was
concentrated under reduced pressure and separated by flash
chromatography (elution with 40% pentane-dichloromethane) to
afford 852 mg (81%) of 4b as a light yellow oil. Crystallization
from methanol gave white crystals: mp 200-202 °C; IR (KBr)
Pyrolysis of Cycloadduct 4b. A solution of 4b (150 mg, 0.285
mmol) in xylenes (4 mL) was heated in a sealed V-vial at 155 °C
for 60 h. The solution was cooled to room temperature, and the
reaction mixture was concentrated under reduced pressure. The
residue was triturated with hot methanol and filtered. The white
solid was washed with methanol and dried to afford 41 mg (27%)
of 2,2,4-triphenyl-3-(p-toluenesulfonyl)-2H-naphthalen-1-one (5b),
obtained as white crystals: mp 294.5-295.5 °C (from dichloro-
1
1595, 1450, 1312, 1304, 1143 cm-1; H NMR (300 MHz) δ 8.05
(d, J ) 6.7 Hz, 2H), 7.81 (d, J ) 6.7 Hz, 1H), 7.57-7.37 (m, 5H),
7.34-7.21 (m, 6H), 7.16 (d, J ) 7.2 Hz, 1H), 7.09 (d, J ) 8.2 Hz,
1H), 7.07 (d, J ) 7.2 Hz, 1H), 6.89 (d, J ) 7.2 Hz, 2H), 6.71-
6.62 (m, 4H), 2.17 (s, 3H); 13C NMR (75 MHz) δ 167.1, 153.4,
149.9, 149.6, 143.2, 136.9, 133.9, 132.5, 132.2, 129.33, 129.32,
methane-methanol); IR (KBr) 1680, 1590, 1449, 1323, 1151 cm-1
;
1H NMR (300 MHz) δ 8.03-7.98 (m, 1H), 7.80-7.73 (m, 4H),
7.47-7.29 (m, 11H), 7.12 (d, J ) 7.2 Hz, 2H), 6.73 (d, J ) 8.2
Hz, 2H), 6.71-6.65 (m, 1H), 6.00 (d, J ) 8.7 Hz, 2H), 2.26 (s,
3H); 13C NMR (75 MHz) δ 198.2, 147.9, 145.5, 143.0, 139.2, 139.1,
137.9, 134.7, 134.5, 131.1, 130.8, 130.7, 129.2, 128.3, 128.12,
128.07, 128.03, 127.98, 127.8, 127.7, 66.8, 21.4; MS (m/z, %) 371
(M+ - Ts, 100), 309 (12), 293 (13), 265 (15). Anal. Calcd for
C35H26O3S: C, 79.82; H, 4.98. Found: C, 80.13; H, 4.96. The
structure was confirmed by X-ray crystallography (see Supporting
Information).
(21) We thank a reviewer for suggesting an alternative pathway for the
conversion of 8b to 9b via the zwitterionic intermediate 27b, a possibility
that we cannot rule out at this time. Zwitterionic intermediates have been
proposed in the somewhat related photochemical rearrangements of cyclo-
hexadienones and bicyclo[3.1.0]hex-3-en-2-ones (skeletal isomers of
oxepins), but this has not been without controversy. For some key references,
see: (a) Zimmerman, H. E.; Schuster, D. I. J. Am. Chem. Soc. 1961, 83,
4486. (b) Schultz, A. G.; Reilly, J. J. Am. Chem. Soc.1992, 114, 5068. (c)
Zimmerman, H. E.; Pasteris, R. J. J. Org. Chem. 1980, 45, 4864. (d)
Schuster, D. I. Acc. Chem. Res. 1978, 11, 65. For a different point of view,
see: (e) Go´mez, I.; Olivella, S.; Reguero, M.; Riera, A.; Sole´, A. J. Am.
Chem. Soc. 2002, 124, 15375.
The methanol filtrate was concentrated under reduced pressure
and purified by flash chromatography on silica gel (elution with
20% pentane-dichloromethane) to afford 84 mg (56%) of 1,1,4-
triphenyl-3-(p-toluenesulfonyl)-1H-naphthalen-2-one (6b), obtained
as yellow crystals: mp 187-193 °C (from methanol); IR (KBr)
1700, 1684, 1443, 1321, 1148 cm-1; 1H NMR (300 MHz) δ 7.47-
7.40 (m, 3H), 7.39-7.16 (m, 12H), 7.04 (d, J ) 8.2 Hz, 2H), 6.95
(dd, J ) 8.2, 1.5 Hz, 1H), 6.82-6.76 (m, 4H), 6.73 (dd, J ) 7.7,
1.5 Hz, 1H), 2.39 (s, 3H); 13C NMR (75 MHz) δ 195.0, 156.3,
144.2, 143.4, 139.2, 137.5, 134.8, 134.3, 132.2, 131.5, 131.4, 131.2,
(22) Back, T. G.; Collins, S.; Kerr, R. G. J. Org. Chem. 1983, 48, 3077.
5258 J. Org. Chem., Vol. 71, No. 14, 2006

Rearrangements of Diels-Alder Cycloadducts
130.2, 129.0, 128.8, 128.7, 128.2, 128.1, 127.9, 127.72, 127.68,
69.6, 21.5; MS (m/z, %) 526 (M+, 0.5), 371 (58), 330 (100), 265
(40); HRMS calcd for C35H26O3S (M+), 526.1603; found, 526.1635.
Anal. Calcd for C35H26O3S: C, 79.82; H, 4.98. Found: C, 79.68;
H, 5.25. The structure was confirmed by X-ray crystallography (see
Supporting Information).
131.2, 131.1, 131.0, 130.2, 129.5, 129.1, 129.0, 128.6, 128.1, 128.0,
127.9, 127.8, 127.7, 127.5, 127.4, 126.8, 21.5; MS (m/z, %) 526
(M+, 1.2), 372 (27), 343 (26), 265 (31), 105 (100). Anal. Calcd
for C35H26O3S: C, 79.82; H, 4.98. Found: C, 79.62; H, 4.94. The
structure was confirmed by X-ray crystallography (see Supporting
Information).
Acid-Catalyzed Rearrangement of Cycloadduct 4a. A solution
of 4a (16 mg, 0.032 mmol) in 5 mL of acetic acid and 0.5 mL of
concentrated HCl was stirred at room temperature for 1 d to afford
16 mg (quantitative) of 5a as a homogeneous colorless oil with
properties identical to those of 5a obtained via pyrolysis of 4a (vide
infra).
Further elution (15% ethyl acetate-hexanes) afforded 85 mg
(42%) of 1-benzoyl-1,2-diphenyl-3-(p-toluenesulfonyl)-1H-indene
(9b) as white crystals: mp 133-134 °C (from ethyl acetate-
1
hexanes); IR (KBr) 1670, 1443, 1323, 1148 cm-1; H NMR (400
MHz) δ 8.39 (d, J ) 7.9 Hz, 1H), 7.59 (d, J ) 8.2 Hz, 2H), 7.56
(m, 1H), 7.42 (m, 1H), 7.40 (m, 1H), 7.36 (d, J ) 7.5 Hz, 2H),
7.34 (m, 1H), 7.26 (d, J ) 6.4 Hz, 1H), 7.23 (d, J ) 7.1 Hz, 1H),
7.18 (d, J ) 8.2 Hz, 2H), 7.14 (d, J ) 7.7 Hz, 2H), 7.11 (d, J )
7.6 Hz, 2H), 7.05 (t, J ) 7.8 Hz, 2H), 6.65 (d, J ) 7.4 Hz, 2H),
6.37 (d, J ) 7.7 Hz, 2H), 2.38 (s, 3H); 13C NMR (75 MHz) δ
195.9, 160.3, 144.1, 143.3, 140.6, 140.0, 137.9, 137.3, 136.3, 132.4,
132.2, 129.7, 129.3, 129.1, 129.0, 128.6, 128.2, 128.1, 127.9, 127.8,
127.7, 127.4, 126.6, 125.6, 123.9, 79.5, 21.4; MS (m/z, %) 526
(M+, 0.7), 371 (73), 265 (53), 105 (100); HRMS calcd for
C35H26O3S (M+), 526.1603; found, 526.1590. Anal. Calcd for
C35H26O3S: C, 79.82; H, 4.98. Found: C, 79.47; H, 4.81. See
Supporting Information for HMBC and HMQC correlations for 9b.
Photolysis of Benzoxepin 8b. A solution of 8b (53 mg, 0.10
mmol) in 3 mL of dichloromethane was irradiated for 2 d, as in
the preceding experiments. The solvent was evaporated, and the
residue was separated by flash chromatography (14% ethyl acetate-
hexanes) to afford 21 mg (40%) of recovered 8b, followed by 29
mg (55%) of 9b.
Reactions in the Presence of BHT. A solution of 4a (44 mg,
0.087 mmol) and BHT (3.8 mg, 0.017 mmol) in xylenes (2 mL)
was heated in a sealed V-vial at 150 °C for 60 h. After the solution
was cooled to room temperature, the reaction mixture was
concentrated under reduced pressure and dried to afford 48 mg of
a yellow solid that contained 5a and 7a (vide supra) in the ratio of
about 1:1 (NMR analysis).
The above reaction was repeated with 4a (51 mg, 0.10 mmol)
and BHT (44 mg, 0.20 mmol). The product again contained 5a
and 7a in the ratio of about 1:1 (NMR analysis).
Acid-Catalyzed Rearrangement of Cycloadduct 4b. A solution
of 4b (10 mg, 0.019 mmol) in acetic acid (5 mL) and 0.5 mL of
concentrated HCl was stirred at room temperature for 4 d to afford
10 mg (quantitative) of a yellow oil that consisted of ketones 5b
and 6b (vide infra) in the ratio of 2:1 (NMR analysis).
Hydrogenation and MCPBA Oxidation of 7a. Product 7a (89
mg, 0.18 mmol) was dissolved in 8 mL of methanol, and palladium
hydroxide on carbon (64 mg) was added. The mixture was
hydrogenated at 1 atm for 4 d. After filtration of the mixture through
a pad of Celite, the methanol was evaporated, and the residue was
separated by flash chromatography (elution with 40% pentane-
dichloromethane) to afford 78 mg (88%) of 14a as a colorless oil:
1
IR (film) 1598, 1439, 1316, 1151 cm-1; H NMR (300 MHz) δ
7.57-7.42 (m, 3H), 7.40-7.17 (m, 11H), 7.17-7.07 (m, 4H),
3.09-2.98 (m, 2H), 2.38 (s, 3H), 1.50-1.38 (m, 2H), 1.08 (sextet,
J ) 7.2 Hz, 2H), 0.65 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz) δ
142.7, 142.6, 141.7, 139.0, 137.6, 137.1, 136.2, 134.7, 132.1, 130.9,
130.3, 129.2, 128.4, 128.2, 128.0, 127.5, 127.2, 127.1, 126.5, 126.2,
125.9, 34.1, 31.6, 23.1, 21.5, 13.4; MS (m/z, %) 490 (M+, 53),
455 (100), 291 (53); HRMS calcd for C33H30O2S (M+), 490.1967;
found, 490.1989.
A solution of 14a (38 mg, 0.077 mmol) and MCPBA (77%, 1.0
mmol) in benzene (3 mL) was sealed in a V-vial and heated at 90
°C for 62 h. After the solution was cooled to room temperature,
the reaction mixture was washed with 10% aqueous KHCO3
solution, and the aqueous layer was extracted with dichloromethane.
The organic layer was dried and evaporated, and the residue was
purified by flash chromatography (elution with 40% pentane-
dichloromethane) to afford 19 mg (50%) of the starting material
and 13 mg (34%) of ketone 5a, identical to the sample prepared
from 4a.
Photolysis of Cycloadduct 4a. A solution of 4a (30 mg, 0.057
mmol) in 4 mL of dichloromethane was irradiated for 2 d in a
Rayonet reactor equipped with 300 nm lamps. The solvent was
evaporated, and the residue was purified by flash chromatography
(15% ethyl acetate-hexanes) to afford 24 mg (80%) of ketone 5a.
Photolysis of Cycloadduct 4b. A solution of 4b (203 mg, 0.386
mmol) in 4 mL of dichloromethane was irradiated for 2 d, as in
the preceding experiment. The solvent was evaporated, and the
residue was purified by flash chromatography (14% ethyl acetate-
hexanes) to afford 103 mg (51%) of 2,3,7-triphenyl-6-(p-toluene-
sulfonyl)-4,5-benzoxepin (8b), obtained as white crystals: mp 225-
227 °C (from hexanes/ethyl acetate); IR (KBr) 1595, 1442, 1318,
1148 cm-1; 1H NMR (300 MHz) δ 8.27 (d, J ) 8.1 Hz, 1H), 7.47
(d, J ) 8.7 Hz, 2H), 7.42-7.08 (m, 17H), 6.75 (d, J ) 8.2 Hz,
1H), 6.56 (d, J ) 7.2 Hz, 2H), 2.39 (s, 3H); 13C NMR (75 MHz)
δ 173.6, 155.8, 143.4, 139.0, 138.7, 138.5, 136.0, 134.0, 133.4,
A solution of 4b (53 mg, 0.10 mmol) and BHT (4.4 mg, 0.020
mmol) in xylenes (2 mL) was heated in a sealed V-vial at 154 °C
for 60 h. After the solution was cooled to room temperature, the
reaction mixture was concentrated under reduced pressure to afford
57 mg of a yellow solid that contained ketones 5b and 6b (vide
supra) in the ratio of 1:2.6 (NMR analysis).
The above reaction was repeated with 4b (39 mg, 0.074 mmol)
and BHT (33 mg, 0.15 mmol). The product again contained 5b
and 6b in the ratio of 1:2.6 (NMR analysis).
Acknowledgment. We thank Merck Frosst (Canada), Ltd.,
and the Natural Sciences and Engineering Research Council of
Canada for financial support.
Supporting Information Available: X-ray crystallographic data
for compounds 4a, 5a, 5b, 6b, and 8b, as well as NMR data for
9b. This material is available free of charge via the Internet at
http://pubs.acs.org.
JO060598E
J. Org. Chem, Vol. 71, No. 14, 2006 5259