Preparation of phenanthrenes by photocyclization of stilbenes containing a tosyl group on the central double bond. A versatile approach to the synthesis of phenanthrenes and phenanthrenoids

Article abstract of DOI:10.1021/jo100742e

We have developed a useful modification of the classical preparation of phenanthrenes by UV irradiation of stilbenes in the presence of an oxidant. This modification involves the irradiation, in the presence of base, of stilbenes possessing a sulfonyl group linked to the central double bond. We have proved that this protocol can be successfully applied for the synthesis of diverse phenanthrenes and phenanthrenoids.

Full text of DOI:10.1021/jo100742e

pubs.acs.org/joc
Preparation of Phenanthrenes by Photocyclization of Stilbenes
Containing a Tosyl Group on the Central Double Bond. A Versatile
Approach to the Synthesis of Phenanthrenes and Phenanthrenoids
†
Ana G. Neo, Carmen Lopez, Victor Romero, Berta Antelo, Jose Delamano,
ꢀ
ꢀ
Antonio Perez, Dolores Fernandez, Jesus F. Almeida, Luis Castedo, and Gabriel Tojo*
ꢀ
ꢀ
ꢀ
´
Departamento de Quımica Organica y Unidad Asociada al C.S.I.C., Universidad de Santiago de Compostela,
15782-Santiago de Compostela, Spain. Present address: Departamento de Quımica Organica e Inorganica,
ꢀ
†
´
ꢀ
ꢀ
ꢀ
Universidad de Extremadura, 10071-Caceres, Spain.
gabriel.tojo@usc.es
Received May 4, 2010
We have developed a useful modification of the classical preparation of phenanthrenes by UV
irradiation of stilbenes in the presence of an oxidant. This modification involves the irradiation, in the
presence of base, of stilbenes possessing a sulfonyl group linked to the central double bond. We have
proved that this protocol can be successfully applied for the synthesis of diverse phenanthrenes and
phenanthrenoids.
Introduction
so-called “phenanthrenoids”, which are similarly prepared
from “stilbenoids.”3
The irradiation with UV light of stilbenes (1) produces an
inicial cis-trans isomerization (Scheme 1).1 The cis isomer
suffers a photochemically allowed conrotatory cyclization
resulting in the formation of the unstable intermediate di-
hydrophenanthrene (2). This intermediate can be aromatized
in situ by an oxidant, leading to a phenanthrene (3). This
probably represents the most useful and versatile synthesis of
phenanthrenes.2 This reaction is equally useful for the pre-
paration of the heterocyclic analogues of phenanthrenes, the
SCHEME 1. Oxidative Photocyclization of Stilbenes
(1) (a) Buckles, R. E. J. Am. Chem. Soc. 1955, 77, 1040. (b) Waldeck,
D. H. Chem. Rev. 1991, 91, 415. (c) Fisher, T.; Ruhmann, R.; Seeboth, A.
J. Chem. Soc., Perkin Trans. 2 1996, 1087. (d) Fischer, E.; Larsen, J.;
ꢀ
Christensen, J. B.; Fourmigue, M.; Madsen, H. E.; Harrit, N. J. Org. Chem.
1996, 61, 6997.
(2) (a) Parker, C. O.; Spoerri, P. E. Nature 1950, 166, 603. (b) Srinivasan,
R. J. Am. Chem. Soc. 1961, 83, 2806. (c) Mallory, F. B.; Wood, C. S.;
Gordon, J. T.; Lindquist, L. C.; Savitz, M. L. J. Am. Chem. Soc. 1962, 84,
4361. (d) Mallory, F. B.; Gordon, J. T.; Wood, C. S. J. Am. Chem. Soc. 1963,
85, 828. (e) Wierchowski, K. L.; Shugar, D.; Katritsky, A. R J. Am. Chem.
Soc. 1963, 85, 829. (f ) Sargent, M. V.; Timmons, C. J. J. Am. Chem. Soc.
1963, 85, 2187. (g) Miyazawa, T.; Koshihara, S.; Segawa, Y.; Kira, M. Chem.
Lett. 1995, 217.
Many oxidants have been used for the transformation of
dihydrophenanthrenes in phenanthrenes, including O2,4 I2,5
I2/CuCl2,6 and TCNE.7 The most commonly used oxidant is
catalytic iodine in the presence of an excess of atmospheric
ꢀ
(3) (a) Leon, P.; Garbay-Jaureguiberry, C.; Le Pecq, J.-B.; Roques, B. P.
(4) (a) Bromberg, A.; Muszkat, K. A. J. Am. Chem. Soc. 1969, 91, 2860.
(b) Rio, G.; Hardy, J. C. Bull. Soc. Chem. Fr. 1970, 3578. (c) Karminski-
Zamola, G.; Pavlicic, D.; Bajic, M.; Blazevic, N. Heterocycles 1991, 32, 2323.
(d) Leigh, W. J.; Lewis, T. J.; Lin, V.; Postigo, J. A. Can. J. Chem. 1996, 74,
263.
Tetrahedron Lett. 1985, 26, 4929. (b) Sudhakar, A.; Katz, T. J.; Yang, B.-W.
J. Am. Chem. Soc. 1986, 108, 2790. (c) Modi, S. P.; Zayed, A.-H.; Archer, S.
J. Org. Chem. 1989, 54, 3084. (d) Prinsen, W. J. C.; Laarhoven, W. H. J. Org.
Chem. 1989, 54, 3689.
6764 J. Org. Chem. 2010, 75, 6764–6770
Published on Web 09/13/2010
DOI: 10.1021/jo100742e
r
2010 American Chemical Society

Neo et al.
JOCArticle
SCHEME 2. Photochemical Preparation of Phenanthrenes
from Stilbenes Containing a Leaving Group at a Phenyl Ring
the central double bond (6) (Scheme 3). This leads to the
formation;via intermediate dihydrotosylphenathrene 7;
of the tosylphenanthrene 8. This compound can be purified
and detosylated in a subsequent reaction by the action of
a reducing agent, such as sodium naphthanelide13 or mag-
nesium in methanol.14
This procedure is very efficient in the preparation of both
phenanthrenes and phenanthrenoids, being particularly use-
ful for the synthesis of certain electron-rich phenanthrenoids
that need to be prepared from electron-rich stilbenoids,
which normally are easily destroyed by oxidants. Particu-
larly, stilbenoids belonging to the bispyrrylethylene kind are
very oxygen sensitive and their photochemical cyclization to
the corresponding pyrroleindoles must be done under very
exacting experimental conditions to succeed.15
The presence of a strongly electron-withdrawing sulfonyl
group in stilbene 6;as in the corresponding stilbenoids;
renders such compounds much more resistant to oxidants, and
therefore allows a much more convenient and higher yielding
photochemical preparation of certain phenathrenoids.
SCHEME 3. Irradiation of Stilbenes Containing a Leaving
Group in the Central Double Bond
Results an Discussion
We speculated that the intermediate dihydrotosylphenan-
threnes 7 could be made to evolve directly to phenanthrenes 3
by the action of a base.16 This would be facilitated by the gain
in aromaticity accompanying the transformation of dihydro-
tosylphenanthrenes 7 into phenanthrenes 3. It is important
to note that this novel photochemical phenanthrene syn-
thesis would allow the direct preparation of phenanthrenes
(3) devoid of tosyl substituents, starting from tosylstilbenes,
in a single operation involving the irradiation of tosylstil-
benes 6 in the presence of a base.
Preparation of the Starting 1,2-Biaryl-1-tosylethylenes.
1,2-Biaryl-1-tosylethylenes (9) can be prepared by based-
induced elimination of β-acetoxy17- and β-halosulfones,18
Wittig-Horner condensation between diethyl sulfonylmethyl
phosphonates and aldehydes,19 Peterson reaction between
R-silylsulfones and aldehydes,20 and oxidation of 1,2-biaryl-
1-arylthioethylenes.21 Rather than employing some of these
well-documented procedures, we opted for the direct;although
less-precedented;method of condensing an aromatic aldehyde
(10) with an arylmethyl aryl sulfone (11) followed by dehydra-
tion of the resulting β-hydroxysulfone (12) (Scheme 4).
oxygen.8 As this oxidizing system leads to the generation of
hydroiodic acid, that can cause side reactions, a new very
useful method was developed, in which an excess of iodine in
the presence of propylene oxide;acting as a hydroiodic acid
scavenger;is employed.9
The use of stilbenes containing a good leaving group at one
of the ortho positions of the aryl substituents (4) allows the
operation of an interesting variant of the photochemical
preparation of phenanthrenes. Thus, the irradiation of stil-
benes (4) (Scheme 2) leads to a dihydrophenathrene 5, that
can be aromatized by the action of a base.10 Leaving groups
commonly employed include Cl and Br. A methoxy group
can also be used as a leaving group, being imperative in this
case the addition of an acid. This results in the operation of a
slightly different mechanism in which the methoxy group is
protonated before the elimination of methanol from the
intermediate dihydrophenanthrene.11
SCHEME 4. Preparation of 1,2-Biaryl-1-tosylethylenes
We described12 the photocyclization in the presence of
an oxidant of stilbenes containing a tosyl group linked to
(5) (a) Laarhoven, W. H.; Peters, W. H. M.; Tinnemans, A. H. A.
€
Tetrahedron 1978, 34, 769. (b) Kaliakoudas, D.; Eugster, C. H.; Ruedi, P.
Helv. Chim. Acta 1990, 73, 48. (c) Jayabalan, L.; Shanmugan, P. Synthesis
1990, 789.
(6) Kellog, R. M.; Groen, M. B.; Wynberg, H. J. Org. Chem. 1967, 32,
3093.
(7) Bendig, J.; Beyermann, M.; Kreysig, D. Tetrahedron Lett. 1977, 3659.
(8) Laarhoven, W. H. Recl. Trav. Chim. Pays Bas 1983, 102, 241.
(9) Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem. 1991,
56, 3769.
(13) Bank, S.; Platz, M. Tetrahedron Lett. 1973, 23, 2097.
(14) Brown, A. C.; Carpino, L. A. J. Org. Chem. 1985, 50, 1749.
(15) Rawal, V. H.; Jones, R. J.; Cava, M. P. Tetrahedron Lett. 1985, 26,
2423.
ꢀ
(16) Almeida, J. F.; Castedo, L.; Fernandez, D.; Neo, A. G.; Romero, V.;
Tojo, G. Org. Lett. 2003, 5, 4939.
(10) (a) Wood, C. S.; Mallory, F. B. J. Org. Chem. 1964, 29, 3373. (b)
Kupchan, S. M.; Wormser, H. C. Tetrahedron Lett. 1965, 6, 359.
(11) Giles, R. G. F.; Sargent, M. V. J. Chem. Soc., Chem. Commun. 1974,
215.
(17) (a) Julia, M.; Launay, M.; Stacino, J.-P.; Verpeaux, J.-N. Tetrahe-
dron Lett. 1982, 23, 2465. (b) Otera, J.; Misawa, H.; Sugimoto, K. J. Org.
Chem. 1986, 51, 3830.
(18) (a) Cristol, S. J.; Pappas, P. J. Org. Chem. 1963, 28, 2066. (b)
´ ´ ´
Carretero, J. C.; Garcıa-Ruano, J. L.; Martınez, M. C.; Rodrıguez, J. H.
Tetrahedron 1987, 43, 4417.
ꢀ
(12) Antelo, B.; Castedo, L.; Delamano, J.; Gomez, A.; Lopez, C.; Tojo,
ꢀ
G. J. Org. Chem. 1996, 61, 1188.
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Neo et al.
SCHEME 5. Dehydration of β-Hydroxysulfones 12a-d
JOCArticle
TABLE 1. Preparation of β-Hydroxysulfonesa
TABLE 2. Condensation of Pyrrolecarbaldehydes with Arylmethylsul-
fonesa
aConditions of condensation: NaOMe, MeOH, Δ.
the addition of mineral acid guarantees good yields of β-hydroxy-
sulfones (12), which are obtained as a single diastereisomer or a
mixture of two diastereoisomers in varying ratios depending in
an unpredicted way on the substrates and the exacting reaction
conditions.
It was found that good and reliable yields for the dehy-
dration of β-hydroxysulfones 12 to tosylstilbenes (9) can
be obtained by the use of mesylchloride and triethylamine
in methylene chloride (Scheme 5). Other dehydrating con-
ditions such as Ac2O/Py, Et3N/CH3COCl, Ac2O/NaOAc,25
or p-TsOH/PhH26 were less successful.
Interestingly, reaction of tosyl aryl sulfones with N-MOM-
pyrrol-2-carbaldehydes (10i) failed to give a useful yield of
the corresponding β-hydroxysulfone. We think that this is due
to the instability of these β-hydroxysulfones which contain
pyrrol rings. Compounds with alcohols located at the benzylic
position of pyrrols are known to be unstable because they have
a tendency to decompose by hydroxy detachment via highly
stabilized carbocations.27 Howewer, pyrrole-containing
β-hydroxysulfones 12e-f are stable compounds and can be
prepared in high yields, because the ester groups located in the
pyrrol rings moderate its electron-richness.
aThe LDA-generated anions of the tosyl derivatives were condensed
at ca. -50 °C with the corresponding aldehyde in THF. Quenching was
carried out by addition of 10% HCl at low temperature.
Aryl tosyl sulfones 11 are easely obtained by benzylation
of commercially available sodium p-toluenesulfinate22 with a
benzyl halide.23 As pyrrylmethyl halides tend to be very
unstable compounds, the preparation of pyrrylmethyl tosyl
sulfones is best done by reaction of pyrryl methyl alcohols
with sodium p-toluenesulfinate in formic acid.24
After considerable experimentation, it was found that the
LDA-generated anions of arylmethyl aryl sulfones (11) react
efficiently in THF with aromatic aldehydes in a highly reliable
manner, resulting in the formation of the desired β-hydroxy-
sulfones, (12) (Table 1). This reaction has a tendency to parti-
ally revert during the elaboration, resulting in capricious yields,
unless it is quenched at low temperature by the addition of 10%
hydrochloric acid. The use of an elaboration protocol including
It was observed that, in variance with other aromatic
aldehydes, pyrrolcarbaldehydes 10e and 10i can be efficiently
(19) Jang, W. B.; Jeon, H. C.; Oh, D. Y. Synth. Commun. 1998, 28, 1253.
(20) (a) Ager, D. J. J. Chem. Soc., Chem. Commun. 1984, 486. (b) Ager,
D. J. J. Chem. Soc., Perkin I 1986, 183.
(21) Cristol, S. J.; Pappas, P. J. Org. Chem. 1963, 28, 2066.
(22) Tietze, L. F.; Eicher, Th. Reaktionem und synthesen im organisch-
chemischem praktikum; Georg Thieme Verlag: New York, 1981; p 342.
(23) Otto, R. B. Chem. Ber. 1880, 13, 1272.
(25) For a list or reagents, with references, see: Larock Comprehensive
Organic Transformations; VCH: New York, 1989; pp 151-152.
(26) Utermoehlen, C. M.; Singh, M.; Lehr, R. E. J. Org. Chem. 1987, 52, 5574.
ꢀ
(27) Castedo, L.; Delamano, J.; Lopez, C.; Lopez, M. B.; Tojo, G.
ꢀ
(24) Balfe, M. P.; Kenyon, I.; Searle, C. E. J. Chem. Soc. 1950, 3309.
Heterocycles 1994, 38, 495.
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SCHEME 6. Preparation of Acetoxystilbenoids
condensed with aryl arylmethylsulfones by heating with
sodium methoxyde in methanol (Table 2). This result is
consistent with the operation of an E1CB dehydrating me-
chanism facilitated by the better leaving group ability of the
hydroxy group in the intermediate β-hydroxysulfones.
Condensation with sodium methoxyde in methanol of
sulfone 11e with pyrrolecarbaldehyde 10e results in partial
hydrolysis of the esters in stilbenoid 9e. We do not believe that
this results from adventitious water, as consistent results are
obtained in various runs. Most probably, the partial hydrolysis
of the esters in 9e results from the 1 equiv of water generated in
the condensation. The methyl ester 9e can be regenerated in
situ by the subsequent addition of an excess of thionyl chloride
after the condensation is complete. This allows the isolation of
89% of tosylstilbenoid 9e in a one-pot reaction.
Thus, two complementary protocols were developed for the
preparation of 1,2-diaryl-1-tosylethenes. The first one, which
is useful for condensation with most aromatic aldehydes,
involves the isolation of an intermediate β-hydroxysulfone,
which is dehydrated with mesyl chloride and triethylamine
(Table 1 and Scheme 5). The second one, which is useful in
condensations with pyrrolecarbaldehydes, employs a direct
condensation mediated by sodium methoxide (Table 2).
Stilbenoids containing an acetoxy group linked to the
central double bond in addition to a tosyl group (9f-h,m)
can be obtained by oxidation of β-hydroxysulfones 12e-h by
DDQ to the corresponding ketones, followed by treatment
with acetyl chloride and triethylamine (Scheme 6).
to the efficient oxidation to ketone 13a in 92%. This successful
result is consistent with the intermediacy of a carbocation
stabilized by the pyrrole ring. Mckittrick and Ganem supplied
experimental data supporting the intermediacy of benzylic
cations in the oxidation of benzyl alcohols to aldehydes or
ketones with DDQ.33 On the other hand, DDQ was shown to
be a very good oxidant for other β-hydroxysulfones such as
12f-h, leading to good yields of ketones 13b-d (Scheme 6).
Additionally, we found that ketone 13d can be obtained by Jones
oxidation34 of alcohol 12h, in a reaction with a much simpler
elaboration than the oxidations with DDQ, in which removal the
secondary product dihydro-1,2-dichoro-4,5-dicyanobenzoqui-
none can be very time consuming.
Treatment of ketones 13a-d with acetyl chloride and
triethylamine led uneventfully to acetoxytosylstilbenoids
9f-h and 9m. In all cases, a single isomer;of unknown
but irrelevant stereochemistry due to the subsequent photo-
chemical isomerization;was obtained.35
SCHEME 7. Preparation of Tosyloxystilbenoids 9j and 9k
Exploratory chemistry for the oxidation of alcohols 12 to
ketones 13 was done on β-hydroxysulfone 12e. It was found that
some oxidants such as KMnO4,28 PCC,29 or BaMnO430 cause
the reversion of the condensation leading to 12e, resulting in the
isolation of pyrrolecarbaldehyde 10e and sulfone 11e. Other
oxidants, such as DMSO/TFAA/Et3N31 or PPh3þBF4-32, cause
the dehydration of β-hydroxysulfone 12e to tosylstilbenoid 9e.
After substantial experimentation, it was found that treatment of
β-hydroxysulfone 12e with DDQ in boiling chlorobenzene leads
Ketones 13c-d can be transformed into stilbenoids, con-
taining a tosyloxy group located at the central double bond
in addition to a tosyl group, by treatment with tosyl chloride
and triethylamine (Scheme 7).
As in acetoxytosylstilbenoids 9f-h,m, tosyloxystilbenoids
9j-k are obtained as a single isomer of unknown but
irrelevant stereochemistry.
(33) McKittrick, B. A.; Ganem, B. J. Org. Chem. 1985, 50, 5897.
(34) (a) Bowden, K.; Heilbron, I. M.; Jones, E. R. H.; Weedon, B. C. L.
J. Chem. Soc. 1946, 39. (b) Bowers, A.; Halsall, T. G.; Jones, E. R. H.; Lemin,
A. J. J. Chem. Soc. 1953, 2548.
(35) It is possible to obtain stilbenoids 9 directly from hydroxysulfones 12
in a one-pot reaction, involving DDQ in chlorobenzene, followed by addition
of excess of AcCl and Et3N. Although good yields of stilbenoids 9 can
obtained, we do not recommend this procedure as it leads to a complex
purification of stilbenoids 9.
(28) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Pedrini, P. J. Org. Chem.
1990, 55, 1439.
(29) Nemoto, H.; Nagai, M.; Fukumoto, K.; Kametani, T. J. Org. Chem.
1985, 50, 2764.
(30) Shea, K. J.; Gilman, J. W.; Haffner, C. D.; Dougherty, T .K. J. Am.
Chem. Soc. 1986, 108, 4953.
(31) Omura., K.; Sharma, A. K.; Swern, D. J. Org. Chem. 1976, 41, 957.
(32) Jung, M. E.; Brown, R. W. Tetrahedron Lett. 1978, 31, 2771.
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TABLE 3. Photochemical Cyclization of Tosylstilbenes and Stilbenoids
in the Presence of Oxidant
TABLE 4. Detosylation of Tosylphenanthrenes and Tosylphenanthrenoidsa
aReagents and conditions: Mg (50 equiv), MeOH, rt. bReagents and
conditions: Na (11 equiv), naphthalene (13 equiv), THF, -78 °C.
aPyrex filter, EtOH, I2 (0.10 equiv), air. bPyrex filter, PhH, I2 (1.1
equiv), propylene oxide (150 equiv), Ar.
to use sodium naphthanylide in cool THF. The detosylation
with magnesium in methanol requires an induction period
of uncertain duration marked by the beginning of a con-
spicuous reaction of metallic magnesium with the solvent.
Very low yields are obtained when a delay is observed for the
outset of the reaction of magnesium with methanol, as
witnessed by the evolution of bubbles of gaseous hydrogen
from the metallic shavings.
The photochemical cyclization in the presence of an
oxidant of stilbenes and stilbenoids, as in Table 3, followed
by detosylation, as shown in Table 4, represents a new and
versatile method for the preparation of phenanthrenes and
phenanthrenoids that have the great advantage of the ready
availability of the starting tosylstilbenes and stilbenoids.
This methodology can be further improved by subjecting
the tosylstilbenes and stilbenoids to photocyclization in the
presence of a base, whereby the final detosylated phenan-
threne or phenanthrenoid can be directly obtained, as shown
in the next section of this paper.
Photochemical Cyclization of Tosylstilbenes in the Presence
of an Oxidant. Irradiation of tosylstilbenes and stilbenoids
9a-i and 9l,m in benzene36 in the presence of 1 equiv of
iodine and an excess of propylene oxide, under Katz0s con-
ditions,38 leads to the corresponding tosylphenanthrenes and
phenanthrenoids 14a-i and 14l,m (Table 3), a fact that
proves that a tosyl group exerts no interference with the
photochemical cyclization of stilbenes. The use of Katz0s
conditions for the photochemical cyclization of stilbenes and
stilbenoids, as opposed to the use of the more common
protocole involving catalytic iodine and atmospheric oxy-
gen, guarantees a consistent better yield in most cyclizations.
In our experience, for the obtention of good yields of
stilbenes under classical conditions, an excess of oxygen
must be guaranteed by continuous liberal bubbling of air
through the cooled reaction solution, this being particularly
important in photocyclizations on a multigram scale.
Photochemical Cyclization of Tosylstilbenes in the Presence
of a Base. Stilbene 9a and stilbenoid 9i were singled out in
order to check the empirical soundness of the putative
transformation depicted in Scheme 3, in which the irradia-
tion of tosylstilbenes in the presence of a base would lead
directly to a desulfonated phenanthrene. Quite gratifyingly,
it was found that regardless of the base or the solvent tried, in
all essays some amount of the desired detosylated phena-
threne 15a or phenanthrenoid 15i was produced (Scheme 8).
Detosylation of phenanthrenes and phenanthrenoids
14a-e,i,m can be done either with magnesium in methanol14
or with sodium naphthanylide13 (Table 4). Although the use
of magnesium in methanol gives generally better yields and is
more facile from the experimental point of view, as this
reaction is highly irreproducible, it can be more convenient
(36) Longbin, L.; Bingwei, Y.; Katz, T. J.; Poindexter, M. K. J. Org.
Chem. 1991, 56, 3769.
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SCHEME 8. Photochemical Cyclization of Stilbene 9a and Stilbenoid 9i in the Presence of a Base
TABLE 5. Photochemical Cyclization of Tosylstilbenes with DBU in
THFa
SCHEME 9. Mechanism of the Photochemical Cyclization in
the Presence of a Base
This reaction was also carried out with triflylstilbenes, whose
UV irradiation in the presence of base generates the corres-
ponding phenanthrenes. This work is in preparation for pub-
lication.
Interestingly, stilbenoids 9j-k, possessing both a tosyl ( p-Me-
Ph-S(O)2-) and tosyloxy (p-Me-Ph-S(O)2O-) group linked to
the central double bond, suffer loss of the tosyl group. This
happens regardless of the much better leaving group ability
of the tosyloxy anion (TsO-) versus a Tosyl anion (Ts-).
Scheme 9 shows a mechanism that is consistent with this fact.
The key dihydrophenanthrene 17 suffers abstraction of a proton
leading to the sulfone-stabilized anion 18. This anion evolves by
protonation followed by elimination of TsH. A parallel mecha-
nism resulting in detachment of the tosyloxy group is not viable,
because no sulfone-stabilized anion is possible.
Sulfones are known to suffer carbon-sulfur bond break-
age on UV irradiation.37 This poses the possibility of an
alternative mechanism, in which a photocyclization in the
presence of adventitious oxygen leads to a tosylphenathrene
that is detosylated under the action of UV light. In fact, we
aThe tosylstilbenes and stilbenoids were irradiated as a 0.2 M solution
in dry THF containing 5 equiv of DBU.
Interestingly, best yields where obtained when DBU;which is
the strongest base among amines;was used. This suggest that
the slow step in these reactions is not the photochemical step,
but the base-induced transformation of an intermediate tosyl-
dihydrophenanthrene into the detosylated phenanthrene.
As the best yields were obtained with DBU in dry THF, these
conditions were tried in a number of tosylstilbenes and stil-
benoids, resulting in consistent good yields of the corresponding
detosylated phenanthrenes and phenanthrenoids (Table 5).16
(37) (a) Laarhoven, W. H.; Cuppen, Th. J. H. M. Tetrahedron Lett. 1966,
ꢀ
41, 5003. (b) Zen, S.; Tashima, S.; Koto, S. Bull. Chem. Soc. Jpn. 1968, 41,
3025. (c) Nakai, M.; Furukawa, N.; Oae, S.; Nakabayashi, T. Bull. Chem.
Soc. Jpn. 1972, 45, 1117. (d) Szarek, W. A.; Dmytraczenko, A. Synthesis
1974, 579. (e) Chang, C.-D.; Hullar, T. J. Carbohydr. Res. 1977, 54, 217. (f )
Givens, R. S.; Matuszewski, B. Tetrahedron Lett. 1978, 19, 861. (g) Berki,
R. J.; Binkley, E. R.; Binkley, R. W.; Hehemann, D. G.; Koholic, D. J.;
Masnovi, J. Carbohydr. Chem. 1996, 15, 33.
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SCHEME 10. Detosylation of Tosylstilbene 14a
found that tosylstilbene 16a suffers detosylation by irradia-
tion in the presence of several bases (Scheme 10).
I2 (1.1 equiv), and propylene oxide (150 equiv) in dry benzene
was irradiated under Ar through a Pyrex filter with a 450 W
Hannovia medium pressure mercury lamp. After 2-10 h, a
workup similar to that of procedure A gave the phenantrenoid.
Methyl 5-Acetoxy-8-methoxy-3-metoxymethyl-4-tosyl-3H-
benz[d]indole-1-carboxylate, 14g. 14g was obtained in 82% yield
with procedure A. Mp 163-164 °C (hexane:EtOAc). 1H NMR
(CDCl3, 250 MHz) δ 9.42 (d, J = 2.5 Hz, 1H), 8.24 (s, 1H), 7.60
(s, 1H), 7.59 (d, J = 8 Hz, 2H), 7.20 (d, J = 8 Hz, 2H), 7.13 (dd,
J1 = 2.5, J2 = 9 Hz, 1H), 5.86 (s, 2H), 4.06 (s, 3H), 3.95 (s, 3H),
2.95 (s, 3H), 2.39 (s, 3H), 2.37 (s, 3H). UV (EtOH) 326, 272, 216
nm. MS (EI, 75 eV, m/z) 511 (Mþ•, 11), 469 (100), 437 (35), 315
(41), 139 (26). Anal. Calcd for C26H24NO8S: C 61.17, H 4.74, N
2.74. Found: C 60.78, H 4.77, N 2.53.
Methyl 5-Acetoxy-3-metoxymethyl-4-tosyl-7,8,9-trimethoxy-
3H-benz[d ]indole-1-carboxylate, 14h. 14h was obtained in 100%
employing procedure A and in 94% employing procedure B. Mp
165 -167 °C (hexane/EtOAc). 1H NMR (CDCl3, 250 MHz) δ
7.74 (s, 1H), 7.67 (d, J = 8 Hz, 2H), 7.25 (d, J = 8 Hz, 2H), 6.79
(s, 1H), 5.85 (s, 2H), 4.06 (s, 3H), 3.91 (s, 3H), 3.85 (s, 3H), 3.74
(s, 3H), 2.96 (s, 3H), 2.40 (s, 6H). 13C NMR (CDCl3, 62.83 MHz)
δ 168.7, 167.5, 152.6, 148.6, 145.2, 144.9, 143.9, 141.4, 131.6,
129.5, 127.7, 126.3, 121.4, 120.8, 119.1, 118.8, 114.8, 98.8, 83.4,
61.2, 56.3, 55.9, 51.5, 21.4, 20.8. UV (EtOH) 334, 256, 212 nm.
MS (EI, 75 eV, m/z) 571 (Mþ•, 12), 529 (45), 497 (16), 375 (100).
Photochemical Cyclization of Tosylstilbenoids in the Presence
of a Base. A solution of stilbenoid (1 equiv) and DBU (5 equiv) in
dry THF was irradiated with a 450 W medium pressure Hanovia
mercury lamp until no substantial amount of starting compound
was detected by TLC. The reaction mixture was poured onto
H2O, HCl (10%) was added, and the resulting mixture was
extracted with CH2Cl2. The combined organic extracts were dried
(Na2SO4) and concentrated, leading to a residue that was puri-
fied by flash chromatography (SiO2, EtOAc-hexane gradient),
affording the corresponding phenanthrenoids.
Also, we found that irradiation of tosylphenanthrene 14a
in THF during 11 h in the presence of DBU yields quantita-
tively the detosylated phenanthrene 15a. However, this
photochemical detosylation procedure seems to be restricted
to certain aryl sulfones, as we found no reaction in the case of
p-tolyl p-tolylmethyl sulfone and allyl p-tolyl sulfone.
In our opinion, this mechanistically intriguing deto-
sylation38 is not operating in the photocyclization in the pre-
sence of a base for the following reasons:
(1) No adventitious oxygen was present in the experiments
shown in Scheme 8 and Table 5. We checked the unaerobicity
of the experimental settings by irradiating tosylstilbene 9a, in
the absence of oxidant or base, resulting only in a E-Z
photoisomerization with no formation of phenanthrene at all.
(2) No photochemical detosylation of tosylphenanthrene
was observed when CaCO3 was used as base (Scheme 10)
while this base is effective in the photocyclization of tosyl-
stilbene 9a, resulting in the formation of detosylated phen-
anthrene 15a (Scheme 8).
We have proved that tosylstilbenes and stilbenoids are
easily prepared compounds that can be transformed effi-
ciently in phenanthrenes and phenanthrenoids by UV irra-
diation in the presence of base. This represents a novel
preparation of phenanthrenes and phenanthrenoids that
may find ample use for the synthesis of this important and
broad type of compounds.
Experimental Section
Air- and moisture-sensitive reactions were performed in flame-
dried round-bottomed flasks fitted with rubber septa under a
positive pressure of argon. Air-andmoisture-sensitive liquids and
solutions were transferred via syringe or stainless steel cannula.
2-Thiophenaldehyde, 2-furanaldehyde, p-anisaldehyde, 3,4,5-tri-
methoxybelzaldehyde, and p-tolualdehyde were purchased from
commercial sources and used without purification.
Preparation of Key Compouds. Photochemical Cyclization of
Tosylstilbenoids in the Presence of an Oxidant. Procedure A: A
water-cooled solution of tosylstilbenoid (1 equiv) and I2 (0.1
equiv) in ethanol was irradiated through a Pyrex filter with a 450
W Hannovia medium pressure mercury lamp, while it was being
oxygenated by a stream of air. After 5-15 h, a saturated
aqueous solution of Na2S2O5 was added and most of the ethanol
was removed in the rotatory evaporator. Extraction with
CH2Cl2, drying (Na2SO4), and concentration gave a residue
that was purified by flash chromatography (SiO2, hexane:
EtOAc gradient) giving the desired phenanthrenoid. Proce-
dure B: A water-cooled solution of tosylstilbenoid (1 equiv),
Spectroscopic data of 15k: Mp 129-131 °C (hexane/EtOAc). 1H
NMR (CDCl3, 250 MHz) δ 7.75 (d, J = 8 Hz, 2H), 7,49 (s, 1H),
7.33 (s, 1H), 7.24 (d, J = 8 Hz, 2H), 6,97 (s, 1H), 5.37 (s, 2H), 3.97
(s, 3H), 3.83 (s, 3H), 3.77 (s, 3H), 3.72 (s, 3H), 3.20 (s, 3H), 2.39 (s,
3H). 13C NMR (CDCl3, 62.83 MHz) δ 168.07 (C), 151.42 (C),
148.53 (C), 145.47 (C), 142.27 (C), 142.23 (C), 132.87 (C), 130.85
(C), 129.79 (CH), 128.51 (CH), 128.14 (CH), 121.16 (C), 118.45
(C), 116.18 (C), 113.72 (C), 104.748 (CH), 98.14 (CH), 77.98 (CH2),
61.09 (CH3), 61.01 (CH3), 56.14 (CH3), 55.65 (CH3), 51.73 (CH3),
21.62 (CH3) ppm. UV (λ max, EtOH) 346, 310, 256, 228, 206 nm.
MS (EI, 75 eV, m/z) 529 (Mþ•, 5), 374 (100), 44 (4). HMRS (EI, 75
eV) calcd 529.1046, found 529.1430. Anal. Calcd for C26H27NO9S:
C 58.97, H 5.13, N 2.64. Found: C 58.93, H 4.84, N 2.78.
Acknowledgment. We thank the Spanish Ministry of Science
and Technology (SAF2001-3120) and the Xunta de Galicia
(PGIDIT02RAG20901PR and PGIDIT02PXIC20902PN) for
financial support.
(38) The mechanism does not seem to involve a carbon-sulfur bond
breakage, resulting in a carbon radical that would abstract a proton from the
solvent, as irradiation of p-tolyl p-tolylmethyl sulfone and allyl p-tolyl
sulfone in the presense of DBU leads to recovery of the starting compounds.
In both compounds a carbon-sulfur bond breakage would be particularly
easy as it would produce very stabilized p-methylbenzyl or allyl radicals.
Supporting Information Available: General procedure to
obtain all compounds, characterization for new products, and
copies 1H and 13C MNR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
6770 J. Org. Chem. Vol. 75, No. 20, 2010