1188
J . Org. Chem. 1996, 61, 1188-1189
Communications
Sch em e 1. Oxid a tive P h otocycliza tion of
Stilben oid s
P h otoch em ica l Rin g Closu r e of
1-Tosyl-1,2-d ia r yleth en es
Berta Antelo, Luis Castedo, J ose´ Delamano,
Ana Go´mez, Carmen Lo´pez, and Gabriel Tojo*
Departamento de Quı´mica Orga´nica y Seccio´n de Alcaloides
del CSIC, Universidad de Santiago de Compostela,†
15706-Santiago de Compostela, Spain
Received August 7, 1995
UV irradiation of 1,2-diarylethenes (1a , 2a ) leads to
E-Z isomerization followed by conrotatory cyclization to
the dihydroaromatic 3a . When the irradiation is carried
out in the presence of an oxidant, the dihydroaromatics
3 may produce good yields of the tricyclic aromatics 4.1
This oxidative cyclization has been extensively used
for the preparation of numerous compounds of type 4 in
which Ar and Ar′ are benzene rings (phenanthrenes).
Nevertheless, its application to the synthesis of hetero-
cycles has been rather limited.2 This is probably due to
either (1) the sensitivity of heterocycles, particulary
electron-rich ones like pyrroles, to the oxidants necessary
for the aromatization of the dihydro intermediates 3 or
(2) the different π-π* excited state distribution in
heterocyclic diarylethenes relative to stilbenes.
Here we describe a novel strategy involving the intro-
duction of an electron-withdrawing sulfonyl group in the
starting diarylethenes 1 and 2. The 1,2-diaryl-1-sulfo-
nylethenes 1b and 2b are easily prepared stable crystal-
line solids which upon oxidative irradiation give good
yields of sulfonyl tricyclic heterocycles 4b without detect-
able desulfonylation. Unlike the sulfonyl compounds 1b
and 2b, 1,2-diarylethenes with a pyrrole or thiophene
ring and no stabilizing electron-withdrawing group are
reported to be “very light sensitive, quickly becoming
dark in room light”.2a The tricyclic heterocycles 4a may
easily be obtained by reductive desulfonylation of the
sulfonyl heterocycles 4b.
desired tosylstilbenoid 7b together with the acids result-
ing from partial hydrolysis of the esters by the equivalent
of water released upon condensation. Reesterification
was easily carried out by adding 23 equiv of thionyl
chloride and refluxing for 1 h. This one-flask procedure
allowed the isolation of an 89% yield of tosyl diester 7b.
When these NaOMe-catalyzed condensations were
tried on furan or thiophenecarbaldehydes, the tosyl
stilbenoid yields were low or erratic. We believe that this
was due to a Cannizzaro side reaction, to which less
electron-rich aromatic aldehydes are prone. However,
treatment of sulfones 6a and 10 with BuLi (1.1 equiv) in
THF at -78 °C, followed by sequential addition of
thiophene-2-carbaldehyde or furan-2-carbaldehyde and
HCl (10%) at -40 °C, allowed the isolation of alcohols
13 and 16 in 96 and 91% yield, respectively, as a mixture
of diastereoisomers. Slow addition of 5 equiv of mesyl
chloride over a cooled (-78 °C) solution of alcohols 13 or
16 and Et3N (10 equiv) in CH2Cl2, followed by stirring
at room temperature, yielded the sulfonyl stilbenoids 14
(88%) and 17 (97%).
UV irradiation5 of water-cooled solutions of tosylstil-
benoids 7a ,b, 14, and 17 in ethanol containing catalytic
iodine led to the corresponding tosylphenanthrenoids in
46-89% yield. Alternatively, the cyclization conditions
of Katz et al.,6 involving the addition of 1 equiv of iodide
and excess propylene oxide (CAUTION: propylene oxide
is carcinogenic), gave consistently good yields (82-90%)
of the corresponding tosylphenanthrenoids. While ir-
radiation of stilbenoid 11 under Katz’s conditions af-
forded a 90% yield of the desired phenanthrenoid 12a ,
we were not able to isolate any sizeable amount of 12a
using O2/catalytic I2 as oxidants.
Condensation of sulfone 6a 3 or benzyl tosyl sulfone
(10)4 with N-(methoxymethylpyrrole)-2-carbaldehyde (5a)3
using NaOMe (50 equiv) in boiling MeOH gave the tosyl
stilbenoids 7a and 11 in 78% and 76% yield, respectively.
(The stereochemistry about the central double bond of
these stilbenoids, and all others prepared in this work,
is unknown but is irrelevant for our purposes because
UV irradiation induces rapid E-Z isomerization, afford-
ing the desired isomers for the photochemical cyclization.)
Under the same conditions, condensation of sulfone 6b3
with pyrrolecarbaldehyde 5b3 led to a mixture of the
Finally, the tosyl group was removed either simply
with magnesium in methanol7 or, generally with better,
less erratic yields, with sodium dihydronaphthalenidyl
at -78 °C.8
In conclusion, we have developed a simple, efficient,
three- or four-step synthesis of heterocyclic phenan-
threnoids. Its application to the preparation of biologi-
† The authors wish to dedicate this paper to commemorate the 5th
centenary of the University of Santiago de Compostela (1495-1995).
(1) Mallory, F. B.; Mallory, C. W. Org. Reac. 1984, 30, 1.
(2) For some recent successful photochemical synthesis of hetero-
cyclic phenanthrenoids see: (a) Rawal, V. H.; J ones, R. J .; Cava, M.
P. Tetrahedron. Lett. 1985, 26, 2423. (b) Pascale, L.; Garbay-J au-
reguiberry, C.; Le Pecq, J . B.; Roques, B. P. Tetrahedron Lett. 1985,
26, 4929. Beccalli, E. M.; Marchesini, A.; Pilati, T. Tetrahedron 1993,
49, 4741. Das, B. P.; Nuss, M. E.; Boykin, D. W. J . Med. Chem. 1974,
17, 516. Karminski-Zamola, G.; Pavlicic, D.; Bajic, M.; Blazevic, N.
Heterocycles 1991, 12, 2323. Modi, S. P.; Zayed, A. H.; Archer, S. J .
Org. Chem. 1989, 54, 3084. Pelaprat, D.; Oberlin, R.; Le Guen, I.;
Roques, B. P. J . Med. Chem. 1980, 23, 1330.
(5) A 450 W Hanovia medium-pressure UV lamp and Pyrex filter
were used. A stream of air was passed through the solution. Batches
of 0.1-1 g were irradiated during 3-18 h.
(6) Longin, L.; Bingwei, Y.; Katz, T. J .; Poindexter, M. K. J . Org.
Chem. 1991, 56, 3769.
(7) Brown, A. C.; Carpino, L. A. J . Org. Chem. 1985, 50, 1749.
(8) Bank, S.; Platz, M. Tetrahedron Lett. 1973, 23, 2097.
(3) Castedo, L.; Delamano, J .; Lo´pez, C.; Lo´pez, M. B.; Tojo, G.
Heterocycles 1994, 38, 495.
(4) Otto, R. B. Dtsch. Chem. Ges. 1880, 13, 1272.
0022-3263/96/1961-1188$12.00/0 © 1996 American Chemical Society
Antelo, Berta
