Palladium-catalyzed cascade reaction of α,β-unsaturated sulfones with aryl iodides

Article abstract of DOI:10.1002/chem.200390173

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of α,β-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions (Pd(OAc)₂ as catalyst, Ag₂-CO₃ as base in DMF at 120°C) takes place mainly by a cascade process, involving one unit of the alkene and three units of the aryl iodide, to afford a substituted 9-phenylsulfonyl-9,10-dihydrophenanthrene, The dominant formation of this 3:1 coupling product, instead of the Heck trisubstituted olefin, shows that aromatic C-H activation processes can compete with the usually fast syn β-hydrogen elimination step in the Heck arylation of an acyclic olefin. The structural scope of this palladium-catalyzed cascade arylation of α,β-unsaturated sulfones has proved to be wide with regard to substitution at the β-position (alkyl, aryl, or alkenyl substitution), substitution at the sulfone unit (alkyl or phenyl sulfones), and configuration at the C=C bond (trans or cis). Moreover, although less favored than in the case of the arylation of α,β-unsaturated sulfones, similarly substituted 9,10-dihydrophenanthrenes have also been obtained in the case of α,β-unsaturated phosphine oxides and α,β-unsaturated phosphonate esters. A Pd⁰-pd^II-pd^IV mechanistic pathway involving the successive formation of highly electrophilic σ-alkylpalladium intermediates and palladacycles is proposed for this multi-component arylation.

Full text of DOI:10.1002/chem.200390173

FULL PAPER
Palladium-Catalyzed Cascade Reaction of a,b-Unsaturated Sulfones with
Aryl Iodides
[a]
Pablo Mauleo¬n, Angel A.Nu nez, Ine¬s Alonso, and Juan C.Carretero*
¬ ƒ
Abstract: Unlike traditionally used acy-
clic 1,2-disubstituted alkenes, the reac-
tion of a,b-unsaturated phenyl sulfones
with aryl iodides under Heck reaction
conditions (Pd(OAc)2 as catalyst, Ag2-
CO3 as base in DMF at 1200C) takes
place mainly by a cascade process,
involving one unit of the alkene and
three units of the aryl iodide, to afford a
substituted 9-phenylsulfonyl-9,10-dihy-
drophenanthrene. The dominant forma-
tion of this 3:1 coupling product, instead
of the Heck trisubstituted olefin, shows
can compete with the usually fast syn b-
hydrogen elimination step in the Heck
arylation of an acyclic olefin. The struc-
tural scope of this palladium-catalyzed
cascade arylation of a,b-unsaturated
sulfones has proved to be wide with
regard to substitution at the b-position
(alkyl, aryl, or alkenyl substitution),
substitution at the sulfone unit (alkyl
or phenyl sulfones), and configuration at
ˆ
the C Cbond ( trans or cis). Moreover,
although less favored than in the case of
the arylation of a,b-unsaturated sul-
fones, similarly substituted 9,10-dihy-
drophenanthrenes have also been ob-
tained in the case of a,b-unsaturated
phosphine oxides and a,b-unsaturated
phosphonate esters. A Pd0 PdII PdIV
mechanistic pathway involving the suc-
cessive formation of highly electrophilic
s-alkylpalladium intermediates and pal-
ladacycles is proposed for this multi-
component arylation.
Keywords:
C H activation
¥
domino reactions ¥ Heck reaction ¥
palladium ¥ sulfones
À
that aromatic C H activation processes
like a,b-unsaturated carbonyl compounds[4] and a,b-unsatu-
rated sulfoxides[5] are employed (Scheme 1).
Introduction
Since its discovery in the late 1960s,[1] the palladium-catalyzed
arylation or vinylation of alkenes (the Heck reaction) has
received increasing attention, becoming one of the most
R1
H
R1
R2
R1
H
EWG
Pd0
EWG
β-H-elim.
À
+
versatile and synthetically useful methods for C Cbond
R2
Pd
base
EWG
R2
X
formation used today.[2] Owing to the high sensitivity of the
Heck reaction to steric factors, the vast majority of the huge
number of Heck reactions reported to date deal either with
intramolecular versions of this reaction[3] or with intermolec-
ular processes on terminal olefins and cycloalkenes.[2] In
recent years, however, considerable progress has been ach-
ieved in the stereoselective synthesis of acyclic, trisubstituted
olefins by Heck reaction of organic halides with 1,2-disub-
stituted olefins, in particular when electronically poor olefins
X
Scheme 1. Synthesis of trisubstituted alkenes by Heck reaction. EWG ˆ
electron-withdrawing group ˆ CO2R, COR, CN, SOAr; R1 ˆ alkyl or aryl,
R2 ˆ aryl or alkenyl.
As part of our ongoing research focused on the develop-
ment of highly stereoselective methods with readily available
functionalized a,b-unsaturated sulfones[6], we envisaged that
acyclic b,b'-disubstituted, a,b-unsaturated sulfones could be
stereoselectively prepared by simple Heck reactions of the
corresponding b-substituted, a,b-unsaturated sulfone. In fact,
Fuchs et al. have reported several examples of intramolecular
Heck reactions of a,b-unsaturated sulfones.[7]
¬
¬
ƒ
[a] Prof. J. C. Carretero, P. Mauleon, A. A. Nunez, Dr. I. Alonso
¬
Departamento de QuÌmica Organica
Facultad de Ciencias
Contrary to these precedents, we describe herein that the
intermolecular palladium-catalyzed reaction of b-substituted,
a,b-unsaturated sulfones with a large excess of iodobenzene
(or p-substituted iodoarenes), in the presence of Ag2CO3 as
base, occurs mainly through a complex cascade reaction in
which three molecules of iodobenzene and one molecule of
vinyl sulfone are involved, affording 1-phenyl-9-phenylsulf-
¬
Universidad Autonoma de Madrid
28049 Madrid (Spain)
Fax : (‡34)913973966
E-mail: juancarlos.carretero@uam.es
Supporting information for this article, including experimental proce-
dures and spectroscopic and analytical data for all compounds not
presented in the experimental section, is available on the WWW under
http://www.chemeuj.org or from the author.
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J. C. Carretero et al.
FULL PAPER
onyl-9,10-dihydrophenanthrenes, rather than the expected
Heck trisubstituted olefin[8] (Scheme 2). The formation of this
Ph
Ph
Pd0
X
À
3:1 coupling product, in which four C Cbonds are formed in
Pd-X
Pd
À
a single synthetic step, indicates that ortho C H activation
processes[9] can compete favorably with the seemingly obvious
I
II
final b-hydrogen elimination step of a Heck reaction.
and/or
and/or
Ph
R
SO2Ph
Ph
R
2:1 adduct
1:1 adduct
PhI (excess)
R
+
SO2Ph
Pd(OAc)2
Ag2CO3
SO2Ph
minor
product
main
product
and/or
Ph
Scheme 2. Palladium-catalyzed arylation of a,b-unsaturated sulfones.
3:1 adduct
2:2 adduct
Scheme 3. Palladium-catalyzed arylation of norbornene.
As far as we know such a palladium catalyzed cascade
arylation of an acyclic alkene has not been previously
reported. The most comparable results were those described
by the groups of Catellani and de Meijere in the palladium-
catalyzed reactions of aryl halides with norbornene.[10] This
very reactive bicyclic alkene has been widely used in
interrupted Heck reactions and in a variety of cascade
processes[11] because the final syn b-hydrogen elimination
step is structurally not feasible. Thus, in this case the insertion
step generates the long-lived s-alkylpalladium intermediate
(I) that, being unable to undergo b-hydrogen elimination,
Results and Discussion
Search for the optimal experimental conditions: When our
model trans-substituted a,b-unsaturated sulfone 1a[13] was
treated with iodobenzene in the presence of Pd(OAc)2
(10 mol%) as catalyst and K2CO3 or Cs2CO3 as base in
DMF at 1200C, we only detected the basic isomerization of
the vinyl sulfone 1a to the allyl sulfone 2.[14] On the other
hand, a sluggish reaction was observed using a typical mild
base such as Et3N. Therefore, we turned our attention to the
use of Ag2CO3, a base which proved to be very effective in
our previous studies of Heck reactions of a,b-unsaturated
sulfoxides.[5] Under these conditions (Pd(OAc)2 10 mol%,
Ag2CO3 200 mol%, DMF, 1200C, 72 h) the reaction of 1a with
an equimolar amount of iodobenzene afforded a mixture of
the starting vinyl sulfone 1a, the allyl sulfone 2, the expected
Heck product 3a, and, unexpectedly, the dihydrophenan-
threne 4a (Table 1, entry 1). In agreement with the fact that
the formation of 4a requires three units of iodobenzene, both
the conversion of the reaction and the yield in dihydrophe-
À
undergoes an intramolecular aromatic C H activation proc-
ess with formation of the key 5-membered palladacycle
intermediate (II).[12] Depending on experimental conditions
1:1, 2:1, 3:1, or 2:2 coupling products are finally isolated[10]
(Scheme 3).
Abstract in Spanish: Al contrario de lo que ocurre con otros
¬
alquenos acÌclicos 1,2-disustituidos, la reaccion de Heck de
fenil sulfonas a,b-insaturadas con yoduros de arilo [Pd(OAc)2
como catalizador, Ag2CO3 como base en DMF a 1208C]
¬
¬
transcurre de forma mayoritaria a traves de una reaccion en
¬
cascada que implica la participacion de una unidad de alqueno
y tres de yoduro de arilo, dando lugar a 9-fenilsulfonil-9,10-
¬
dihidrofenantrenos. La formacion de este producto de acopla-
miento 3:1, en lugar de la olefina trisustituida, pone de
Table 1. Palladium-catalyzed reaction of 1a with iodobenzene.[a]
À
¬
¬
manifiesto que procesos de activacion aromatica C H pueden
¬
competir con la etapa de b-eliminacion syn, normalmente
SO2Ph
¬
¬
rapida en procesos de arilacion de Heck de olefinas acÌclicas.
1a
¬
Desde un punto de vista estructural esta reaccion en cascada
PhI
Ag2CO3
¬
presenta un caracter muy general, teniendo lugar con sulfonas
Pd(OAc)2 DMF, 120 °C
Ph
a,b-insaturadas portadoras de sustituyentes alquilo, arilo o
alquenilo en posicion b, sustituyentes alquilo o fenilo en la
unidad de sulfona y configuracion trans o cis en el doble
enlace. Por otra parte, aunque menos favorecido que en el caso
SO2Ph
Ph
¬
SO2Ph
+
+
SO2Ph
¬
2
3a
4a
¬
de las sulfonas, los oxidos de fosfina y los fosfonatos a,b-
Entry
PhI (equiv)
1a:2:3a:4a[b]
¬
¬
insaturados tambien conducen a la formacion de 9,10-dihi-
¬
drofenantrenos. Este proceso de arilacion multicomponente
1
2
3
1
5
10
23:30:26:21
8:5:6:81
1: :5:94
¬
puede explicarse a traves de un ciclo catalÌtico que implica
diversos estados de oxidacion del paladio (Pd -Pd -Pd ) con
0
II
IV
¬
¬
formacion sucesiva de intermedios s-alquilpaladio altamente
[a] Reaction conditions: Ag2CO3 (200 mol%), Pd(OAc)2 (10 mol%),
DMF, 1200C , 72 h, 1[ a] ˆ 0.2m. [b] Evaluated by 1H NMR spectroscopy
of the crude mixtures.
¬
electrofilos y paladaciclos.
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Pd-Catalyzed Cascade Reactions
1511 1520
Table 2. Palladium-catalyzed reaction of trans-a,b-unsaturated sulfones 1
nanthrene 4a were progressively enhanced with increasing
amounts of iodobenzene[15] (Table 1, entries 1 3). In the
presence of 10 equivalents of iodobenzene a clean reaction in
favor of the formation of the domino product 4a was observed
(3a:4a ˆ 5:95, 86% yield, Table 1, entry 3). A further recris-
tallyzation from diethyl ether provided pure dihydrophenan-
threne 4a in 69% overall yield. The structural determination
of 4a was first undertaken by NMR and mass spectrometric
studies and its unequivocal confirmation, including the trans
stereochemistry at C-9/C-10, was established by X-ray crys-
tallographic analysis[16] (Figure 1).
with iodobenzene.[a]
Ph
R
SO2Ph
Ph
R
PhI
R
+
SO2Ph
Pd(OAc)2
Ag2CO3
SO2Ph
1
3
4
Entry Alkene
R
3:4 [%][b]
Yield[c][%] (4[d][%])
1
2
3
4
5
6
7[h]
1a
1b
1c
1d
1e
1 f
1g
iPr
3a:4a ˆ 5:95
86 (69)
[f]
Me
nPent
Cy
3b:4b:5[e] ˆ 11:27:52
3c:4c ˆ 12:88
-
82[g]
3d:4d ˆ 10:90
3e:4e ˆ 3:97
84[g]
Ph
82 (63)
85 (61)
78 (60)
b-Naph 3 f:4 f ˆ 8:92
H
3e:4e ˆ 4:96
[a] Reaction conditions: PhI (10 equiv), Pd(OAc)2 (10 mol%), Ag2CO3
(200 mol%), DMF, 1200C, 3 5 days. [b] Determined by 1H NMR spectro-
scopy of the crude mixtures. [c] Yield in 3 ‡ 4 after flash chromatography
(compound 4 was only partially separated). [d] Yield of pure compound 4
after recrystallization. [e] Compound 5 ˆ 1,2-diphenyl-3-(phenylsulfonyl)-
1-propene. [f] Pure compound 4b could not be separated by chromatog-
raphy or recrystallization. [g] Dihydrophenanthrenes 4c and 4d could not
be crystallized. About 10 15% of pure 4c and 4d were obtained after flash
chromatography [toluene/iPr2O (100:1)]. [h] 250 mol% of Ag2CO3 was
used.
Figure 1. Crystal structure of compound 4a.
tendency of 1b[17] (and probably 3b) to undergo basic
isomerization to the corresponding allyl phenyl sulfone and
ˆ
further Heck reaction on the C Cbond.
Scope of the cascade arylation of a,b-unsaturated phenyl
sulfones: To determine the dependence of the reaction on the
nature of the b-substituent of the a,b-unsaturated sulfone, a
variety of trans-substituted a,b-unsaturated sulfones (sub-
strates 1b f) were treated with iodobenzene under the best
conditions previously found for 1a (Scheme 4, Table 2).
Interestingly, the results were rather homogeneous regardless
A particularly interesting result was obtained from the b-
unsubstituted commercially available phenyl vinyl sulfone
(1g, Table 2, entry 7), which afforded dihydrophenanthrene
4e in high yield. This product is the same as that obtained in
the reaction of the b-phenyl substituted substrate 1e (Table 2,
entry 5), showing that in the reaction of 1g four molecules of
iodobenzene were involved in
the process, with the subsequent
À
formation of five C Cbonds.
This result can be readily ex-
Ph
Ph
Ph
PhI, Ag2CO3
Pd(OAc)2
plained by assuming that the b-
unhindered vinyl sulfone 1g
SO2Ph
Ph
R
SO2Ph
SO2Ph
DMF, 120
C
Ph
first undergoes a very favorable
Heck reaction to afford the
sterically uncongested, trans-
substituted olefin 1e, which in
the presence of an excess of
iodobenzene reacts in situ by
the cascade process to give the
1h, R= H
1i, R= Ph
6
4h (47% from 1h)
(48% from 1i)
Scheme 4. Palladium-catalyzed reaction of dienyl sulfones with iodobenzene.
dihydrophenanthrene 4e. In full agreement with this hypoth-
esis, 1e was isolated in high yield (82% after chromatographic
purification) when the palladium-catalyzed reaction of 1g was
carried out in the presence of a stoichiometric amount of
iodobenzene instead of a tenfold excess.
Although the mixture of products 3 and 4 could not,
because of their very similar chromatographic mobilities, be
completely separated by flash chromatography in any of the
cases, pure compounds 4a, 4e, and 4 f were readily obtained
by further recrystallization from diethyl ether (61 69%
yields).[18] The structure of the dihydrophenanthrenes 4 was
unequivocally established by NMR spectroscopic and mass
of the relatively varied steric and electronic properties of the
substituent in the b-position. Thus, in most cases the cascade
product 4 predominated largely over the Heck product 3 with
both b-alkyl- (Table 2, entries 1, 3, and 4) and b-aryl
substituted vinyl sulfones[13] (Table 2, entries 5 and 6). The
only exception to this general trend was the behavior of the
methyl-substituted vinyl sulfone 1b (Table 2, entry 2). In this
case a more complex mixture of products was obtained, the
dihydrophenanthrene 4b being detected in low yield (27% on
the crude reaction mixture) along with the major formation of
a mixture of monoarylated (3b) and diarylated Heck olefin
products (5). The formation of 5 is most likely due to the high
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J. C. Carretero et al.
FULL PAPER
spectrometric studies,[19] and the structure of the 1,10-diphenyl
dihydrophenanthrene 4e was confirmed by X-ray crystallo-
graphic analysis.[16]
The study of the scope of this reaction was extended to the
case of the vinylogous substrates: the 1-(phenylsulfonyl)-1,3-
dienes 1h and 1i (Scheme 4). The behavior of this type of a,b-
unsaturated sulfone was particularly interesting owing to the
this competitive process to the Heck reaction could also
operate with other types of electronically poor, acyclic
alkenes. To address this question the methyl sulfone 1j, the
sulfonamide 1k, the phosphine oxide 1l, the phosphonate 1m,
the ester 1n, and the phenyl ketone 1o, all with an isopropyl
group in the b-position of the alkene, were treated with PhI/
Pd(OAc)2/Ag2CO3 under the usual conditions. The results are
summarized in Table 3.
ˆ
presence of two potentially reactive C Cbonds. Surprisingly,
despite the different substitution at the terminal position of
the diene, both compounds reacted similarly with excess of
PhI/Ag2CO3 under the usual reaction conditions (Pd(OAc)2,
DMF, 1200C) affording as the main product the same
9-(phenylsulfonyl)-9,10-dihydrophenanthrene 4h[19] (47
48% yield of pure product after chromatographic purification
and recrystallization). The structure of 4h was unequivocally
confirmed by X-ray crystallographic analysis.[16] This result
clearly reveals the quite different reactivity of both types of
Table 3. Palladium-catalyzed reaction of alkenes 1j
o
with iodo-
benzene.[a]
Ph iPr
W
Ph
iPr
PhI
iPr
+
W
Pd(OAc)2
Ag2CO3
W
1
3
4
Entry
Alkene
W
3:4 [%][b]
Yield[c] 4(%)
ˆ
ˆ
C Cbonds of the diene unit. Thus, while the C3 C4 bond
underwent a regioselective Heck arylation at C4 (or double
Heck arylation in the case of 1h), the a,b-unsaturated
phenylsulfonyl moiety reacted according to the cascade
arylation process. In terms of chemical complexity the
behavior of 1h is especially remarkable, since in this case
the process involves the participation of five units of
1
2
3
4
5
6
7
1a
1j
1k
1l
1m
1n
1o
SO2Ph
3a:4a ˆ 5:95
3j:4j ˆ 11:89
3k:4k ˆ 21:79
3l:4l ˆ 53:47
3m:4m ˆ 65:35
3n:4n ˆ 82:18
3o[f]:4o ˆ 91:9
86 (69)[d]
77 (52)[d]
SO2Me
SO2NEt2
P(O)Ph2
PO3Et2
CO2Et
COPh
55
37
24
[e]
-
[e]
À
iodobenzene and the resulting formation of six C Cbonds.
[a] Reaction conditions: PhI (10 equiv), Pd(OAc)2 (10 mol%), Ag2CO3
(200 mol%), DMF, 1200C. [b] Determined by 1H NMR spectroscopy of the
crude mixtures. [c] Yield after flash chromatography. [d] Yield after flash
chromatography and further recrystallization. [e] The minor compounds
4n and 4o could not be completely purified by chromatography or
recrystallization. Significant shifts of these compounds are given in the
experimental section. [f] Mixture of isomers.
From a mechanistic point of view it is interesting to note
that when the reactions of 1h and 1i were performed,
respectively, in the presence of two or one equivalents of PhI
(instead of a large excess), the 4,4-diphenyldiene 6 was
detected in both cases in the crude mixtures. This result
suggests that 6 could be a common intermediate in the
cascade arylation of 1h and 1i.
Gratifyingly, the methyl sulfone 1j (Table 3, entry 2) and
the sulfonamide 1k (Table 3, entry 3) gave similar results to
that obtained from the corresponding phenyl sulfone 1a
(Table 3, entry 1). Thus, in both cases the reaction with
iodobenzene occurred mainly through the domino arylation
pathway (3j:4j ˆ 11:89 and 3k:4k ˆ 21:79).
According with the structural assignment of compounds 4,
their reductive desulfonylation by treatment with Na-Hg
(MeOH, THF, room temperature) led almost quantitatively
to the corresponding 1-phenyl-10-substituted-9,10-dihydro-
phenanthrenes 7 (Scheme 5). From a synthetic point of view, it
Interestingly this kind of intermolecular cascade arylation is
not exclusively limited to the case of a,b-unsaturated sulfones
and related sulfur compounds. As shown in entries 4 and 5 in
Table 3, the a,b-unsaturated phosphine oxide 1l and the a,b-
unsaturated phosphonate 1m gave substantial amounts of the
corresponding dihydrophenanthrenes 4l and 4m, although
the cascade/Heck selectivity was much poorer (3l:4l ˆ 53:47;
3m:4m ˆ 65:35). After chromatographic separation of these
mixtures, the Heck products 3l and 3m were isolated in 38 and
53% yields, respectively, whereas the products 4l and 4m
were obtained in 37 and 24% yields, respectively.
Scheme 5. Desulfonylation of compounds 4.
By contrast, a very different result was observed in the
arylation of typical p-conjugated, electron-deficient olefins
such as the ester 1n and the enone 1o (entries 6-7). In these
cases only minor amounts of the dihydrophenanthrenes 4
could be detected by NMR spectroscopy, and the Heck
products largely predominated.
should be noted that this two-step sequence, cascade arylation
of a,b-unsaturated sulfones and further desulphonylation,
constitutes an extremely convergent synthesis of 1-phenyl-
substituted 9,10-dihydrophenanthrenes from a benzene de-
rivative.
These results suggest that the relative stabilization of the
Reaction of other electron-deficient alkenes: Having demon-
strated the general scope of the cascade palladium-catalyzed
reaction of a,b-unsaturated phenyl sulfones with iodoarenes
in the presence of Ag2CO3, it was important to determine if
ˆ
C Cbond by p-conjugation with the electron-withdrawing
group could be an important factor in the competition
between Heck reaction and cascade arylation. Thus, in
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Pd-Catalyzed Cascade Reactions
1511 1520
ˆ
agreement with the fact that in the arylation the starting C C
bond is not regenerated, it is observed that the higher the
Since reductive elimination in 10 is not expected to be a very
favorable process owing to the strained nature of the resulting
benzocyclobutane, palladacycle 10 could undergo oxidative
addition of iodobenzene to form the PdIV[21] palladacycle
species[22] 11, which would lead to the s-alkylpalladium
intermediate 12 by a fast reductive elimination process.[23]
The repetition of the same sequence of steps to the second
ˆ
thermodynamic stability of the C Cbond (as in the case of
the p-conjugated olefins 1n and 1o), the lower the formation
of the dihydrophenanthrene product. In other words, in the
case of a,b-unsaturated sulfones, in which it is well known that
the sulfonyl group does not furnish significant stability to the
C Cbond, [14] the Heck reaction is less favored to such extent
that the competitive domino arylation process becomes the
main process.
ˆ
À
ortho C H position (palladacycle formation, oxidative addi-
tion to iodobenzene, and reductive elimination (12 13 14
15)) would furnish the next s-sulfonylalkylpalladium species
(15). Once both ortho positions of the initially inserted
aromatic ring have been substituted, intermediate 15 could
Mechanistic hypothesis: Although the complex multistep
nature of this reaction makes any detailed mechanistic
rationalization very difficult, a Pd0-PdII-PdIV mechanistic
pathway similar to that proposed by Catellani et al. for the
cascade arylation of norbornene can be tentatively pro-
posed[10] (Scheme 6). The oxidative addition of iodobenzene
À
evolve by an aromatic C H activation process on one of the
external phenyl rings to form the seven-membered pallada-
cycle[24] 16. This intermediate would finally undergo a very
favorable reductive elimination process (with formation of
the central six-membered ring), releasing the Pd0 catalyst and
the final product 4.
À
In agreement with the sequence of formation of C Cbonds
depicted in Scheme 6, in the palladium-catalyzed reaction of
1e with para-substituted iodoarenes, such as p-iodotoluene
and ethyl p-iodobenzoate, only the dihydrophenanthrenes
with substitution at the C3 and C7 positions (compounds 17
and 18, Scheme 7) were isolated (about 32% yield after
R
I
Ph
Pd(OAc)2
Ph
+
SO2Ph
SO2Ph
Ag2CO3
1e
R
R
3
7
R
17, R= Me, 32%
18, R= CO2Et, 32%
Scheme 7. Reaction of 1e with p-substituted iodoarenes. Reaction con-
ditions: ArI (10 equiv), Pd(OAc)2 (10 mol%), Ag2CO3 (200 mol%), DMF,
1200C, 11 days.
chromatographic purification and further recrystallization
from diethyl ether).[25] The structures of 17 and 18 were
unequivocally established by mass spectrometry and NMR
spectroscopy experiments (1H NMR, 13CNMR, COSY, and
NOESY)[26]
.
Reaction of cis-substituted a,b-unsaturated sulfones: From a
stereochemical point of view, the exclusive formation of C9/
C10 trans-substituted dihydrophenanthrenes from trans-a,b-
unsaturated sulfones would indicate that the configuration of
the starting alkene is preserved along the reaction course,
which is consistent with an initial syn-carbopalladation step
Scheme 6. Mechanistic proposal (the ligands at the palladium center have
been omitted for clarity).
to the Pd0 catalyst in the presence of Ag2CO3 would give the
cationic phenylpalladium species 8. This species would under-
ˆ
À
go a regioselective syn-insertion to the C Cbond to generate
and further aromatic C H activation processes through the
the sulfonylalkylpalladium intermediate 9. At this point,
unlike the usual behavior of an acyclic alkene in a Heck
arylation, the highly electrophilic complex 9 would evolve
participation of trans-substituted palladacycles as indicated in
Scheme 6. This high stereoselectivity prompted us to inves-
tigate the behavior of a cis-substituted a,b-unsaturated
sulfone, since if a parallel diastereomeric pathway occurred,
C9/C10 cis-substituted dihydrophenanthrenes could be ob-
tained.
À
faster through an aromatic C H activation process, to form
the five-membered palladacycle[20] 10, rather than by syn-b-
hydrogen elimination to afford the minor Heck product 3.
Chem. Eur. J. 2003, 9, No. 7
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1515

J. C. Carretero et al.
FULL PAPER
To properly compare the outcome of the reaction, the pair
of diastereomeric phenyl sulfones trans-1p and cis-1p, with a
™methyl-labeled∫ substituent in the b-position (a p-tolyl
group), were stereoselectively prepared according to reported
procedures[13][27] and treated with iodobenzene/Ag2CO3 in the
presence of a palladium catalyst. In these cases we observed
that the cascade:Heck product ratio was very high when we
H3C
H3C
H
PhI
Pd(OAc)2
SO2Ph
SO2Ph
H
H
Ag2CO3
Pd+
H
cis-1j
20
used
a
palladacycle catalyst[28] instead of Pd(OAc)2
Ph
C-H activ.
(Scheme 8). trans-1p behaved as expected, affording the C9/
C10 trans-substituted dihydrophenanthrene 4p (81% yield),
p-tolyl
C-H activ.
CH3
Ph
SO2Ph
SO2Ph
CH3
Pd
Pd
I
H3C
Ph
[Pd]
+
21
SO2Ph
22
SO2Ph
trans-1p
H3C
Ag2CO3
CH3
Ph Ph
4p, 81%
SO2Ph
Ph
I
Ph Ph
SO2Ph
H3C
H3C
SO2Ph
[Pd]
Ag2CO3
SO2Ph
+
19
H3C
cis-1p
Scheme 9. Mechanistic proposal for the reaction of cis-1p.
19, 52%
H3C
O
Pd
O
o-tol
O
Pd
O
o-tol
moiety as a substituent on the sulfur proved to be critical to
the success of this reaction.[5] Compared to the sluggish
reaction observed from the corresponding phenyl sulfoxides,
we justified the high reactivity of the 2-(N,N-dimethylami-
no)phenyl sulfoxides as a result of the pseudointramolecular
character of the reaction because of the coordination of the
P
Palladacycle catalyst =
P
o-tol o-tol
CH3
Scheme 8. Palladium-catalyzed reaction of trans-1p and cis-1p with
iodobenzene. Reaction conditions: PhI (10 equiv), palladacycle catalyst
(5 mol%), Ag2CO3 (200 mol%), DMF, 1200C.
À
palladium atom to the N,N-dimethylamino group (Pd N
chelation-controlled reaction). These findings prompted us to
investigate the behavior of the corresponding a,b-unsaturated
2-(N,N-dimethylamino)phenyl sulfones 23 under the standard
arylation conditions [PhI, Ag2CO3, Pd(OAc)2].
in which the starting p-tolyl group is bound to the C10
position. Unexpectedly, the reaction of cis-1p also led to the
major formation of a single dihydrophenantrene with trans
stereochemistry at C9/C10, but with the methyl group of the
starting p-tolyl moiety in position C3 of the final dihydrophe-
nanthrene (compound 19, 52% yield).[29] The seemingly
anomalous formation of 19 could be readily explained by
taking into account that, once the syn carbopalladation step
occurred, the resulting s-alkylpalladium intermediate 20
Interestingly, the a,b-unsaturated sulfones 23 behaved as
expected for an acyclic alkene under Heck reaction con-
ditions, affording in each case the corresponding trisubstituted
olefin 25[30] in high yield and with complete E stereoselectivity
(70 85% yield, Scheme 10). The corresponding dihydrophe-
nanthrene was not detected by 1H NMR spectroscopy even in
the presence of the usual large excess of iodobenzene. This
opposite result to that described from sulfones 1 is in
agreement with our assumption that the cascade arylation of
a,b-unsaturated phenyl sulfones requires the participation of
À
would undergo a C H activation process at the p-tolyl moiety,
and not at the phenyl group introduced after the syn
carbopalladation step, in order to avoid the formation of the
cis-substituted palladacycle 21, which is presumably less stable
than the corresponding trans
analogue 22 (Scheme 9).
Ph
NMe2
NMe2
O2
S
PhI
Pd(OAc)2
Reaction of a,b-unsaturated
2-(N,N-dimethylamino)phenyl
R
β-H-elim.
R
SO2
H
SO2
Ag2CO3
Pd
N
sulfones: In our previous stud-
DMF, 120 C
Me2
Ph
R
ies on Heck reactions of a,b-
unsaturated aryl sulfoxides with
PhI/Ag2CO3 the use of the
25a, R= iPr, 85%
25c, R= nPent, 70%
25e, R= Ph, 80%
23
24
Scheme 10. Heck reaction of a,b-unsaturated sulfones 23 with iodobenzene.
2-(N,N-dimethylamino)phenyl
1516
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Chem. Eur. J. 2003, 9, No. 7

Pd-Catalyzed Cascade Reactions
1511 1520
stirring and argon atmosphere. When the starting alkene disappeared by
TLC(3 11 days, the particular reaction time is indicated below for each
case) the mixture was allowed to cool to room temperature and was diluted
with Et2O (20 mL), filtered through celite, washed with water (20 mL),
dried (MgSO4), and evaporated. The residue was purified by flash
chromatography (the eluent is indicated below for each case). Where
indicated, pure samples of dihydrophenanthrenes were obtained by further
recrystallization from Et2O.
highly electrophilic s-alkylpalladium species in order to
À
promote the key ortho C H activation steps. Thus, in the
case of olefins 23 the insertion of the arylpalladium species
ˆ
À
into the C Cbond would presumably lead to the Pd
chelated s-alkylpalladium intermediate 24, which would
undergo a syn b-hydrogen elimination process, and not a
N
À
C H activation process, as a result of the diminished electro-
10-Isopropyl-1-phenyl-9-(phenylsulfonyl)-9,10-dihydrophenanthrene (4a):
Reaction time three days. Eluent hexane/diethyl ether (10:1), 86% yield.
Recrystallization from diethyl ether, 69% overall yield. M.p. 182 1840C;
1H NMR (200 MHz): d ˆ 7.71 7.68 (m, 2H), 7.59 7.23 (m, 8H), 7.16 6.93
(m, 7H), 4.54 (d, J ˆ 1.9 Hz, 1H), 4.07 (dd, J ˆ 1.9 and 7.5 Hz, 1H), 1.35 (m,
1H), 0.53 (d, J ˆ 6.7 Hz, 3H), 0.44 ppm (d, J ˆ 6.7 Hz, 3H); 13CNMR
(75 MHz): d ˆ 142.5, 141.3, 136.4, 135.9, 132.9, 132.7, 131.3, 130.7, 129.8,
128.9, 128.3, 127.9, 127.6, 127.1, 127.0, 123.8, 123.0, 69.0, 40.2, 32.3, 20.8,
philic character of the palladium atom caused by its coordi-
nation with the highly donating nitrogen atom. It should also
À
be noted that conceptually similar Pd N chelation controlled
Heck reactions have been described for other types of alkenes
bearing chains with an appropriately located nitrogen atom.[31]
‡
‡
19.5 ppm; MS (FAB ‡ ): (m/z): 461 [M ‡ Na] , 297 [M À PhSO2] , 255, 154,
95; elemental analysis calcd (%) for C29H26O2S: C79.42, H 5.98, S 7.31;
found: C79.22, H 5.81, S 6.85. Crystal structure data for C 29H26O2S (4a):
crystal size 0.20  0.35  0.25 mm, monoclinic, space group P21/c, a ˆ
13.3746(6), b ˆ 8.8535(5), c ˆ 20.5133(9) ä, b ˆ 106.860(4)0, Vˆ
2324.6(2) ä3, Z ˆ 5, 1calcd ˆ 1.566 MgmÀ3, m ˆ 1.764 mmÀ1, 2qmax ˆ 113.940,
Conclusion
Compared to any other type of acyclic 1,2-disubstituted
alkene, b-substituted a,b-unsaturated phenyl sulfones display
unique behavior under arylation Heck conditions. In the
presence of Ag2CO3 as base, their palladium-catalyzed
reactions (Pd(OAc)2 as catalyst, in DMF at 1200C) with
iodobenzene (or p-substituted iodoarenes) occurred mainly
by a cascade process (involving one molecule of vinyl sulfone
and three molecules of iodobenzene) rather than by a normal
Heck arylation, affording trans-9-(phenylsulfonyl)-9,10-dihy-
drophenanthrenes (compounds 4). This result indicates that,
unlike the usual behavior of an alkene under Heck reaction
conditions, the s-alkylpalladium intermediate formed after
the starting insertion step can evolve faster by successive
CuKa radiation,
l
ˆ 1.54178 ä, 2q/w scans, Tˆ 296 K, absorption
correction: none, 4119 reflections collected, 3076 independent. Refinement
on F 2 for 3076 reflections and 524 parameters gave GOF ˆ 1.053, R1 ˆ
0.0322 and wR2 ˆ 0.0853 for I > 2s(I). Residual electron density À0.313 <
D1 < 0.220 eäÀ3. S, O, and Catoms were refined with anisotropic thermal
displacements parameters and the H atoms with isotropic parameters. The
structure was solved and refined using SHELX-97.[32]
10-n-Pentyl-1-phenyl-9-(phenylsulfonyl)-9,10-dihydrophenanthrene (4c):
Reaction time three days. Eluent hexane/diethyl ether (10:1), 82% yield:
1
(3c:4c ˆ 12:88; 4c was partially separated by chromatography). H NMR
(300 MHz): d ˆ 7.60 7.27 (m, 10H), 7.18 6.96 (m, 7H), 4.35 (d, J ˆ 1.6 Hz,
1H), 4.11 (ddd, J ˆ 1.6, 5.0, and 9.3 Hz, 1H), 1.30 0.66 ppm (m, 11H);
13CNMR (75 MHz): d ˆ 154.5, 153.7, 149.5, 148.4, 147.3, 145.7, 145.1, 145.0,
143.4, 142.8, 142.4, 142.0, 141.3, 141.2, 140.9, 140.6, 140.3, 140.2, 139.8, 139.2,
136.9, 136, 82.8, 47.4, 46.5, 43.6, 38.9, 35.1, 26.8 ppm; HRMS (FAB ‡ ): calcd
À
ortho C H activation steps, with consequent formation of
five-membered palladacycle intermediates, than by a b-
hydrogen elimination process.
‡
for C25H25 ([M À PhSO2] ) 325.1956, found 325.1960.
10-Cyclohexyl-1-phenyl-9-(phenylsulfonyl)-9,10-dihydrophenanthrene
(4d): Reaction time four days. Eluent hexane/diethyl ether (10:1), 84%
yield: (3d:4d ˆ 10:90; 4d was partially separated by chromatography).
1H NMR (300 MHz): d ˆ 7.70 7.68 (m, 2H), 7.62 7.25 (m, 8H), 7.14 6.96
(m, 7H), 4.51 (d, J ˆ 1.6 Hz, 1H), 4.10 (dd, J ˆ 1.7 and 7.1 Hz, 1H), 1.5
0.4 ppm (m, 11H); 13CNMR (75 MHz): d ˆ 142.5, 141.3, 136.5, 136.0, 133.0,
132.6, 132.5, 131.4, 130.7, 129.8, 129.7, 128.9, 128.7, 128.3, 127.9, 127.6, 127.2,
127.0, 123.8, 122.9, 68.9, 42.1, 39.5, 30.9, 29.7, 26.3, 26.2, 25.9 ppm; HRMS
Although not so favorable as in the case of a,b-unsaturated
sulfones, such cascade arylation also occurs with related
electronically poor olefins like a,b-unsaturated sulfonamides,
phosphine oxides, and a,b-unsaturated phosphonates. In
contrast, typical p-conjugated olefins such as a,b-unsaturated
esters and enones almost exclusively afforded the Heck-type
products.
‡
(FAB ‡ ): calcd for C26H25 ([M À PhSO2] ) 337.1956, found 337.1964.
1,10-Diphenyl-9-(phenylsulfonyl)-9,10-dihydrophenanthrene (4e): Reac-
tion time five days. Eluent hexane/diethyl ether (10:1), 82% yield.
Recrystallization from diethyl ether, 63% yield. M.p. 155 1570C;
1H NMR (300 MHz): d ˆ 7.70 7.66 (m, 1H), 7.45 7.01 (m, 19H), 6.72
6.87 (m, 2H), 5.06 (d, J ˆ 1.1 Hz, 1H), 4.4 ppm (d, J ˆ 1.1 Hz, 1H);
13CNMR (75 MHz): d ˆ 142.7, 141.4, 140.3, 136.1, 135.9, 133.7, 132.9, 132.4,
131.2, 130.3, 130.0, 129.0, 128.5, 128.0, 127.9, 127.8, 127.7, 127.6, 127.4, 126.7,
125.4, 123.7, 123.1, 73.3, 41.6 ppm; HRMS (FAB ‡ ): calcd for C32H25O2S
Experimental Section
General: Chemical shifts in NMR spectra are expressed in ppm. All NMR
spectra were obtained in CDCl3 at room temperature. Both chemical shifts
and coupling constants (Hz) were obtained by first order analysis of spin
patterns. High resolution mass spectra were recorded by using FAB
technique. Analitycal thin layer chromatography was performed on DC-
Alufolien 0.2 mm silica gel 60 F254 (MERCK). Visualization was accom-
plished with UV light and ethanolic phosphomolybdic acid solution
followed by heating. Flash chromatography was performed on silica gel
MERCK-60 (230 400 mesh). All reagents were obtained from commercial
suppliers and were used without further purification except for aldehydes,
which were used freshly distilled. DMF was distilled from CaH2. THF was
distilled from sodium/benzophenone. CH2Cl2 was distilled from P2O5. All
reactions involving the use of nBuLi or Pd(OAc)2 were carried out in flame
and oven dried glassware under inert argon atmosphere.
‡
([M ‡ H] ) 473.1575, found 473.1564. Crystal structure data for C32H24O2S
≈
(4e): crystal size 0.07  0.4  0.2 mm, triclinic, space group P1, a ˆ
9.5089(14), b ˆ 10.0130(11), c ˆ 13.1809(12) ä, a ˆ 74.739(8), b ˆ
83.950(9), g ˆ 79.955(10)0, Vˆ 1189.8(2) ä3, Z ˆ 2, 1calcd ˆ 1.319 MgmÀ3
,
m ˆ 1.424 mmÀ1, 2qmax ˆ 114.50, C uKa radiation, l ˆ 1.54178 ä, 2q/w scans,
Tˆ 296 K, absorption correction: empirical (min./max. transmission:
0.3332/0.4135). 3795 reflections collected, 3138 independent. Refinement
on F 2 for 3138 reflections and 533 parameters gave GOF ˆ 1.024, R1 ˆ
0.0318 and wR2 ˆ 0.0863 for I > 2s(I). Residual electron density À0.218 <
D1 < 0.145 eäÀ3. S, O, and Catoms were refined with anisotropic thermal
displacements parameters and the H atoms with isotropic parameters. The
structure was solved and refined using SHELX-97.[32]
General procedure for the preparation of dihydrophenanthrenes (4, 17, 18,
and 19) and characterization data of the main products: A mixture of the
corresponding alkene
200 mol%), Pd(OAc)2 (0.04 mmol, 10 mol%), aryl iodide (4 mmol,
1000 mol%), and DMF (2 mL) was heated at 1200Cunder vigorous
1
(0.4 mmol), silver carbonate (0.8 mmol,
10-b-Naphthyl-1-phenyl-9-(phenylsulfonyl)-9,10-dihydrophenanthrene
(4 f): Reaction time five days. Eluent hexane/diethyl ether (10:1), 85%
yield. Recrystallization from diethyl ether, 61% yield. M.p. 158 1600C;
Chem. Eur. J. 2003, 9, No. 7
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1517

J. C. Carretero et al.
FULL PAPER
1H NMR (300 MHz): d ˆ 8.10 6.90 (m, 24H), 5.28 (d, J ˆ 1.4 Hz, 1H),
4.53 ppm (d, J ˆ 1.4 Hz, 1H); 13CNMR (75 MHz): d ˆ 142.7, 142.5, 140.2,
138.8, 137.7, 136.0, 135.9, 133.8, 133.3, 133.2, 132.9, 132.7, 132.3, 132.2, 130.9,
130.8, 130.3, 130.0, 129.3, 128.9, 128.4, 127.8, 127.4, 126.9, 125.8, 125.7, 125.6,
125.4, 123.7, 123.2, 73.2, 41.7 ppm; HRMS (FAB ‡ ): calcd for C30H21 ([M À
126.6, 123.9, 123.8, 123.2, 61.8, 61.7, 61.6, 61.5, 41.7, 40.1, 40.0, 39.9, 31.7, 31.5,
21.0, 20.0, 16.2, 16.1, 16.0 ppm; HRMS (FAB ‡ ): calcd for C27H32O3P
‡
([M ‡ H] ) 435.2089, found 435.2074.
Significant 1H NMR data of compound (4n): 1H NMR (200 MHz): d ˆ 3.91
(brs, 1H; H9), 3.50 (brd, J ˆ 9.1 Hz, 1H; H10), 0.65 (d, J ˆ 6.5 Hz, 3H;
CH3), 0.42 ppm (d, J ˆ 6.5 Hz, 3H; CH3).
‡
PhSO2] ) 381.1643, found 381.1624.
10-(2,2-Diphenylethenyl)-1-phenyl-9-(phenylsulfonyl)-9,10-dihydrophe-
nanthrene (4h): Reaction time five days. Eluent hexane/diethyl ether
(10:1), 57% yield from 1h, 58% from 1i. Recrystallization from diethyl
ether, 47% yield from 1h, 48% from 1i. 1H NMR (300 MHz): d ˆ 7.68 (m,
1H), 7.49 7.21 (m, 13H), 7.18 6.96 (m, 9H), 6.86 (m, 2H), 6.66 (m, 2H),
5.46 (d, J ˆ 9.1 Hz, 1H), 4.95 (dd, J ˆ 1.8 and 9.1 Hz, 1H), 4.36 ppm (d, J ˆ
1.8 Hz, 1H); 13CNMR (125 MHz): d ˆ 149.4, 143.8, 142.6, 142.3, 140.9,
138.6, 137.1, 136.1, 133.1, 133.0, 132.8, 132.3, 131.0, 130.4, 129.6, 129.5, 129.3,
128.9, 128.8, 128.5, 128.3, 128.2, 127.8, 127.7, 127.5, 126.7, 124.5, 123.8, 71.4,
Significant 1H NMR data of compound (4o): 1H NMR (300 MHz): d ˆ 4.92
(d, J ˆ 1.6 Hz, 1H; H9), 3.38 (dd, J ˆ 1.6 and 9.3 Hz, 1H; H10), 0.87 (d, J ˆ
6.9 Hz, 3H; CH3), 0.45 ppm (d, J ˆ 6.9 Hz, 3H; CH3).
1-Phenyl-9-(phenylsulfonyl)-10-(p-tolyl)-9,10-dihydrophenanthrene (4p):
Reaction time five days (a palladacycle catalyst[28] was used instead of
Pd(OAc)2). Eluent hexane/diethyl ether (10:1), 81% yield. 1H NMR
(300 MHz): d ˆ 7.68 (d, J ˆ 7.3 Hz, 1H), 7.41 (dt, J ˆ 1.8 and 7.1 Hz, 1H),
7.36 7.22 (m, 8H), 7.21 7.11 (m, 2H), 7.10 7.00 (m, 5H), 6.85 (d, J ˆ
8.1 Hz, 2H), 6.59 (d, J ˆ 8.1 Hz, 2H), 5.03 (brs, 1H), 4.39 (d, J ˆ 1.2 Hz,
1H), 2.19 ppm (s, 3H); 13CNMR (75 MHz): d ˆ 142.6, 140.3, 138.4, 136.2,
136.1, 136.0, 135.9, 133.6, 132.9, 132.4, 131.3, 130.4, 129.9, 129.2, 129.0, 128.9,
128.0, 127.7, 127.6, 127.5, 127.3, 125.5, 123.7, 123.0, 73.4, 41.1, 20.9 ppm;
‡
36.3, 15.7 ppm; HRMS (FAB ‡ ): calcd for C34H25 ([M À PhSO2] )
433.1956, found 433.1963. Crystal structure data for C40H30O2S (4h): crystal
size 0.15  0.25  0.20 mm, monoclinic, space group P21, a ˆ 8.62810(10),
b ˆ 14.1813(2), c ˆ 12.91000(10) ä, b ˆ 108.9390(10)0, Vˆ 1494.12(3)ä3,
Z ˆ 2, 1calcd ˆ 1.277 MgmÀ3, m ˆ 1.231 mmÀ1, 2qmax ˆ 141.020, C uKa radiation,
l ˆ 1.54178 ä, 2q/w scans, Tˆ 296 K, absorption correction: SADABS
versus 2.03, 2797 reflections collected. Refinement on F 2 for 2797
reflections, 389 parameters and one restraint gave GOF ˆ 1.044, R1 ˆ
0.0288, and wR2 ˆ 0.0819 for I > 2s(I). Residual electron density
À0.161 < D1 < 0.186 eäÀ3. S, O, and Catoms were refined with anisotropic
‡
HRMS (FAB ‡ ): calcd for C27H21 ([M À PhSO2] ) 345.1643, found
345.1635.
3,7-Dimethyl-10-phenyl-9-(phenylsulfonyl)-1-(p-tolyl)-9,10-dihydrophe-
nanthrene (17): Reaction time 11 days. Eluent hexane/diethyl ether (8:1),
69% Yield. Recrystallization from diethyl ether, yield: 32%. M.p. 210
2120C; 1H NMR (500 MHz): d ˆ 7.53 (d, J ˆ 8.1 Hz, 1H), 7.35 7.30 (m,
1H), 7.20 (dd, J ˆ 1.8 and 8.1 Hz, 1H), 7.10 7.02 (m, 11H), 6.96 (brs, 1H),
6.92 (brs, 1H), 6.93 6.87 (m, 1H), 6.77 6.74 (m, 2H), 5.00 (brs, 1H), 4.34
(d, J ˆ 1.3 Hz, 1H), 2.38 (s, 3H), 2.30 (s, 3H), 2.27 ppm (s, 3H); 13CNMR
(75 MHz): d ˆ 143.1, 142.5, 138.4, 138.2, 137.5, 136.7, 134.5, 134.2, 133.5,
132.9, 131.5, 129.7, 129.5, 129.3, 129.1, 128.6, 128.5, 128.3, 128.2, 128.1, 127.2,
126.1, 124.2, 124.2, 74.4, 42.1, 21.9, 21.8, 21.7 ppm; HRMS (FAB ‡ ): calcd
thermal displacements parameters and the
H atoms with isotropic
parameters. The structure was solved and refined using SHELX-97.[32]
1-Phenyl-9-(methylsulfonyl)-10-isopropyl-9,10-dihydrophenanthrene (4j):
Reaction time 3.5 days. Eluent hexane/diethylether (8:1), 77% yield.
Recrystallization from diethylether, 52% yield. M.p. 167 1710C; 1H NMR
(300 MHz): d ˆ 7.92 (d, J ˆ 8.1 Hz, 1H), 7.82 (d, J ˆ 8.1 Hz, 1H), 7.57 7.36
(m, 9H), 7.25 (dd, J ˆ 1.2 and 7.7 Hz, 1H), 4.26 (s, 1H), 3.93 (d, J ˆ 7.3 Hz,
1H), 2.17 (s, 3H), 1.54 1.42 (m, 1H), 0.55 (d, J ˆ 6.9 Hz, 3H), 0.49 ppm (d,
J ˆ 6.9 Hz, 3H); 13CNMR (75 MHz): d ˆ 144.3, 141.8, 136.0, 134.4, 134.1,
132.9, 132.3, 131.1, 130.7, 129.6, 129.3, 128.8, 128.1, 125.2, 124.5, 68.7, 41.4,
‡
for C29H25 ([M À PhSO2] ) 373.1956, found 373.1941.
3,7-(Diethoxycarbonyl)-1-[4-(ethoxycarbonyl)phenyl]-10-phenyl-9-(phe-
nylsulfonyl)-9,10-dihydrophenanthrene (18): Reaction time 11 days. Elu-
ent hexane/diethyl ether (8:1), 69% yield. Recrystallization from diethyl
ether, 32% yield. M.p. 155 1560C; 1H NMR (500 MHz): d ˆ 8.19 (brs,
1H), 8.15 (brd, J ˆ 8.4 Hz, 1H), 8.02 (d, J ˆ 7.6 Hz, 2H), 7.95 (brd, J ˆ
8.4 Hz, 1H), 7.88 (brs, 1H), 7.76 (brs, 1H), 7.45 7.39 (m, 1H), 7.20 7.05
(m, 9H), 6.67 6.62 (m, 2H), 5.10 (brs, 1H), 4.47 (brs, 1H), 4.50 4.39 (m,
4H), 4.35 (q, J ˆ 7.2 Hz, 2H), 1.45 (t, J ˆ 7.2 Hz, 3H), 1.44 (t, J ˆ 7.1 Hz,
3H), 1.38 ppm (t, J ˆ 7.2 Hz, 3H); 13CNMR (75 MHz): d ˆ 167.0, 166.4,
166.2, 144.4, 142.8, 140.5, 139.7, 137.3, 136.4, 134.2, 134.1, 134.0, 132.2, 132.0,
131.0, 130.8, 130.7, 130.1, 129.7, 129.7, 129.6, 128.9, 128.3, 128.0, 126.4, 125.8,
125.0, 73.2, 62.1, 62.0, 61.8, 42.1, 15.1, 15.0, 14.9 ppm; HRMS (FAB ‡ ):
‡
38.5, 33.3, 21.9, 20.5 ppm; HRMS (EI ‡ ): calcd for C24H24O2S ([M ])
376.1497, found 376.1479.
1-Phenyl-9-(N,N-diethylsulfamoyl)-10-isopropyl-9,10-dihydrophenan-
threne (4k): Reaction time nine days. Eluent hexane/diethyl ether (8:1),
70% yield. Recrystallization from diethyl ether, 55% yield. M.p. 162
1
1660C; H NMR (300 MHz): d ˆ 7.89 (brd, J ˆ 7.7 Hz, 1H), 7.81 (brd, J ˆ
7.7 Hz, 1H), 7.63 7.53 (m, 1H), 7.49 7.28 (m, 7H), 7.21 7.18 (m, 1H), 4.41
(d, J ˆ 1.6 Hz , 1H), 3.88 (dd, J ˆ 7.7 and 1.6 Hz, 1H), 2.86 2.55 (m, 4H),
1.49 1.37 (m, 1H), 0.93 (t, J ˆ 7.1 Hz , 6H), 0.51 (d, J ˆ 6.9 Hz, 3H),
0.48 ppm (d, J ˆ 6.9 Hz, 3H); 13CNMR (75 MHz): d ˆ 143.5, 142.2, 136.7,
135.2, 133.8, 131.8, 131.6, 130.5, 130.1, 128.9, 128.7, 128.3, 127.7, 127.6, 124.9,
123.7, 66.2, 43.4, 41.6, 32.9, 21.7, 20.2, 15.8 ppm; HRMS (EI ‡ ): calcd for
‡
calcd for C35H31O6 ([M À PhSO2] ) 547.2120, found 547.2105.
3-Methyl-1,10-diphenyl-9-(phenylsulfonyl)-9,10-dihydrophenanthrene
(19): Reaction time five days (a palladacycle catalyst was used instead of
Pd(OAc)2)[28]. Eluent hexane/diethyl ether (10:1), 52% yield. 1H NMR
(500 MHz): d ˆ 7.65 (brd, J ˆ 7.9 Hz, 1H), 7.38 (dt, J ˆ 2.0 and 6.9 Hz, 1H),
7.36 7.32 (m, 1H), 7.31 7.27 (m, 5H), 7.22 (dt, J ˆ 0.9 and 7.3 Hz, 1H),
7.09 7.02 (m, 9H), 6.95 (brs, 1H), 6.73 6.68 (m, 2H), 5.00 (s, 1H), 4.38 (s,
1H), 2.30 ppm (s, 3H); 13CNMR (75 MHz): d ˆ 142.5, 141.5, 140.4, 137.0,
136.1, 136.0, 133.7, 132.3, 131.1, 129.9, 129.0, 128.9, 128.5, 128.2, 128.0, 127.9,
127.8, 127.7, 127.3, 126.6, 125.6, 123.9, 123.7, 73.6, 41.3, 21.1 ppm; HRMS
‡
C27H31NO2S ([M ]) 433.2076, found 433.2055.
9-(Diphenylphosphoryl)-10-isopropyl-1-phenyl-9,10-dihydrophenanthrene
(4l): Reaction time five days. Eluent hexane/ethyl acetate (1:1), 37% yield.
1H NMR (300 MHz): d ˆ 7.87 7.79 (m, 2H), 7.62 7.58 (m, 1H), 7.57 7.53
(m, 1H), 7.51 7.44 (m, 2H), 7.41 7.35 (m, 2H), 7.34 7.19 (m, 5H), 7.10
6.97 (m, 8H), 6.80 6.75 (m, 1H), 4.21 (dd, J ˆ 1.4 and 17.6 Hz, 1H), 3.91
3.85 (m, 1H), 1.48 1.34 (m, 1H), 0.68 (d, J ˆ 6.8 Hz, 3H), 0.39 ppm (d, J ˆ
6.8 Hz, 3H); 13CNMR (75 MHz) (splitting of signals due to coupling with
the phosphorus atom): d ˆ 142.2, 141.9, 137.0, 136.9, 134.4, 134.3, 133.9,
133.5, 132.2, 131.9, 131.8, 131.7, 131.6, 131.5, 131.4, 130.9, 130.8, 130.3, 130.2,
130.1, 130.0, 129.9, 129.8, 129.5, 129.3, 128.5, 128.4, 128.0, 127.9, 127.8, 127.3,
127.2, 127.1, 127.0, 126.8, 126.5, 124.3, 124.2, 123.0, 44.2, 43.3, 39.6, 39.5, 32.2,
‡
(FAB ‡ ): calcd for C27H21 ([M À PhSO2] ) 345.1643, found 345.1634.
Diphenyl [(E)-3-methyl-2-phenyl-1-butenyl]phosphine oxide (3l) b: Re-
action time five days. Eluent hexane/ethyl acetate (1:1), yield 38%.
1H NMR (300 MHz): d ˆ 7.82 7.74 (m, 4H), 7.52 7.38 (m, 6H), 7.34 7.27
(m, 3H), 7.23 7.18 (m, 2H), 5.94 (m, J ˆ 25.7 Hz, 1H), 3.79 (m, 1H),
0.95 ppm (d, J ˆ 6.87 Hz, 6H); 13CNMR (75 MHz) (splitting of signals due
to coupling with the phosphorus atom): d ˆ 171.6, 171.5, 141.1, 140.9, 135.6,
134.2, 131.5, 131.4, 130.9, 130.8, 128.6, 128.4, 128.3, 128.2, 127.7, 127.6, 127.5,
127.2, 127.1, 127.0, 121.0, 119.6, 32.7, 32.6, 21.0 ppm; HRMS (FAB ‡ ): calcd
‡
32.0, 21.0, 20.1 ppm; HRMS (FAB ‡ ): calcd for C35H32OP ([M ‡ H] )
499.2191, found 499.2198.
10-Isopropyl-9-(diethoxyphosphoryl)-1-phenyl-9,10-dihydrophenanthrene
(4m): Reaction time five days. Eluent hexane/ethyl acetate (1:1), 24%
yield. 1H NMR (300 MHz): d ˆ 7.81 (brd, J ˆ 7.9 Hz, 1H), 7.75 (brd, J ˆ
7.9 Hz, 1H), 7.64 (brs, 1H), 7.49 7.41 (brt, J ˆ 7.4 Hz, 2H), 7.40 7.23 (m,
6H), 7.22 7.16 (m, 1H), 3.91 3.74 (m, 3H), 3.62 3.49 (m, 2H), 3.40 (ddq,
J ˆ 7.1, 8.3, and 10.1 Hz, 1H), 1.48 1.33 (m, 1H), 1.10 (t, J ˆ 7.1 Hz, 3H),
0.99 (t, J ˆ 7.1 Hz, 3H), 0.59 (t, J ˆ 6.8 Hz, 3H), 0.39 ppm (t, J ˆ 6.8 Hz,
3H); 13CNMR (75 MHz) (splitting of signals due to the coupling with the
phosphorus atom): d ˆ 142.7, 141.9, 135.5, 135.5, 135.4, 135.3, 134.1, 134.0,
130.6, 130.5, 130.4, 130.3, 130.1, 128.0, 127.9, 127.8, 127.7, 127.6, 126.8, 126.7,
‡
for C23H24OP ([M ‡ H] ) 347.1565, found 347.1563.
Diethyl [(E)-3-methyl-2-phenyl-1-butenyl] phosphonate (3m): Reaction
time five days. Eluent, hexane/ethyl acetate (1:1), yield 53%. 1H NMR
(300 MHz): d ˆ 7.35 7.29 (m, 3H), 7.19 7.15 (m, 2H), 5.43 (d, J ˆ 18.8 Hz,
1H), 4.12 (m, 4H), 3.80 3.68 (m, 1H), 1.35 (t, J ˆ 7.1 Hz, 6H), 1.08 ppm (d,
J ˆ 6.87 Hz, 6H); 13CNMR (75 MHz) (splitting of signals due to coupling
with the phosphorus atom): d ˆ 170.6, 170.4, 141.0, 140.6, 127.7, 127.6, 127.6,
1518
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Chem. Eur. J. 2003, 9, No. 7

Pd-Catalyzed Cascade Reactions
1511 1520
116.5, 114.1, 61.5, 61.4, 32.5, 32.4, 21.3, 16.4, 16.3 ppm; HRMS (FAB ‡ ):
126.5, 125.2, 123.9, 46.1, 31.7, 30.0, 27.8, 22.3, 13.9 ppm; HRMS (FAB ‡ ):
‡
‡
calcd for C15H24O3P ([M ]) 283.1463, found 283.1473.
calcd for C21H28NO2S ([M ‡ H] ) 358.1841, found 358.1847.
(E)-1-[2-(N,N-dimethylamino)phenylsulfonyl]-2,2-diphenylethene (25e):
Eluent hexane/diethyl ether (10:1), 80% yield. M.p. 132 1340C;
1H NMR (300 MHz): d ˆ 7.49 7.46 (m, 2H), 7.40 7.23 (m, 8H), 7.20
7.16 (m, 2H), 7.03 6.93 (m, 3H), 2.77 ppm (s, 6H); 13CNMR (75 MHz):
d ˆ 153.2, 152.2, 139.6, 135.6, 133.9, 130.1, 129.8, 129.7, 129.6, 128.5, 128.3,
128.2, 128.0, 127.4, 124.8, 123.2, 46.2 ppm; HRMS (FAB ‡ ): calcd for
(E)-1,2-Diphenyl-3-methyl-3-pentenone (3o) (isolated as major isomer in
a mixture of isomers): Reaction time: 1.5 days. Eluent hexane/dichloro-
methane (1:1), 71% yield. 1H NMR (300 MHz): d ˆ 7.69 7.61 (m, 2H),
7.46 7.27 (m, 8H), 6.06 (s, 1H), 3.00 (s, 1H), 1.74 (s, 3H), 1.61 ppm (s, 3H);
13CNMR (75 MHz): d ˆ 149.8, 143.1, 133.0, 128.5, 128.3, 128.1, 127.3, 126.6,
125.8, 107.2, 88.9, 29.8, 27.5 ppm.
‡
C21H28NO2S ([M ‡ H] ) 364.1371, found 364.1386.
General procedure for the preparation of dihydrophenanthrenes 7: Under
an argon atmosphere, recently prepared, finely divided Na Hg (6%,
200 mg) was added to a solution of dihydrophenanthrene 4 (1 mmol) in a
THF/MeOH (1:1) mixture (1 mL). After the mixture had been stirred at
room temperature for 12 h, another portion of Na Hg (100 mg) was added
to bring the reaction to completion. The reaction mixture was then washed
with NaOH (2m, 3 mL), the organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (3 Â 10 mL). The combined organic layers
were dried (MgSO4) and the solvent was evaporated. The residue was
purified by flash chromatography to give the corresponding dihydrophen-
anthrene 7 (the eluent and yield are indicated below for each case).
Acknowledgements
Financial support of this work by the Ministerio de Ciencia y TecnologÌa
(BQU2000 0226) is gratefully acknowledged. P. M. also thanks the
Ministerio de Ciencia y TecnologÌa for a predoctoral fellowship.
[1] a) T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581;
b) R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5518.
10-Isopropyl-1-phenyl-9,10-dihydrophenanthrene (7a) b: Reaction time
24 h. Eluent hexane/diethyl ether (4:1), 99% yield. M.p. 106 1070C;
1H NMR (300 MHz): d ˆ 7.81 (t, J ˆ 7.4 Hz, 2H), 7.51 7.11 (m, 10H), 3.19
2.90 (m, 3H), 1.49 1.25 (m, 1H), 0.64 (d, J ˆ 6.7 Hz, 3H), 0.39 ppm (d, J ˆ
6.7 Hz, 3H); 13CNMR (75 MHz): d ˆ 142.3, 142.2, 138.7, 135.5, 135.2, 134.2,
129.9, 129.4, 128.5, 127.9, 127.5, 126.7, 126.5, 126.2, 123.5, 123.4, 40.2, 32.1,
[2] For recent reviews on the Heck reaction see: a) I. P. Beletskaya, A. V.
Cheprakov, Chem. Rev. 2000, 100, 3009; b) C. Amatore, A. Jutand,
Acc. Chem. Res. 2000, 33, 314; c) A. de Meijere, F. E. Meyer in Metal-
Catalyzed Cross-Coupling Reactions (Eds.: F. Diederich, P. J. Stang),
Wiley-VCH, Weinheim, 1998, Chapter 3; d) J. T. Link, L. E. Overman
in Metal-Catalyzed Cross-Coupling Reactions (Eds.: F. Diederich, P. J.
Stang), Wiley-VCH, Weinheim, 1998, Chapter 6; e) G. T. Crisp, Chem.
Soc. Rev. 1998, 27, 427; f) M. Shibasaki, C. D. J. Boden, A. Kojima,
Tetrahedron 1997, 53, 7371; g) W. Cabri, I. Candiani, Acc. Chem. Res.
1995, 28, 2; h) A. de Meijere, F. E. Meyer, Angew. Chem. 1994, 106,
2473; Angew. Chem. Int. Ed. Engl. 1994, 33, 2379. See, also: i) J. Tsuji,
Palladium Reagents and Catalysts; Innovations in Organic Synthesis,
Wiley, Chichester, 1995.
‡
29.7, 21.4, 20.4 ppm; HRMS (FAB ‡ ): calcd for C23H22 ([M ]) 298.1721,
found 298.1733.
1,10-Diphenyl-9,10-dihydrophenanthrene (7e): Reaction time 24 h. Eluent
hexane/diethyl ether (4:1), 99% yield. M.p. 154 1550C; 1H NMR
(300 MHz): d ˆ 7.94 (dd, J ˆ 1.0 and 8.0 Hz, 1H), 7.91 (d, J ˆ 8.0 Hz, 1H),
7.47 (t, J ˆ 7.7 Hz, 2H), 7.37 6.96 (m, 12H), 6.83 6.78 (m, 2H), 4.25 (dd,
J ˆ 2.0 and 6.0 Hz, 1H), 3.35 (dd, J ˆ 6.0 and 15.0 Hz, 1H), 2.96 ppm (dd,
J ˆ 2.0 and 15.0 Hz, 1H); 13CNMR (75 MHz): d ˆ 141.0, 136.0, 135.3, 135.0,
134.3, 129.7, 129.2, 128.8, 128.3, 127.9, 127.8, 127.7, 127.3, 127.1, 126.9, 125.7,
[3] For a review on the intramolecular Heck reaction, see: S. E. Gibson,
R. J. Middleton, Contemp. Org. Synth. 1996, 3, 447.
‡
123.6, 40.5, 37.5 ppm; HRMS (FAB ‡ ): calcd for C26H20 (M ) 332.1565,
found 332.1559.
[4] For synthesis of trisubstituted olefins by Heck reaction of b-
substituted a,b-unsaturated esters, nitriles, aldehydes, or ketones,
see: a) A. F. Littke, G. C. Fu, J. Am. Chem. Soc. 2001, 123, 6989; b) X.
Du, M. Suguro, K. Hirabayashi, A. Mori, T. Nishikata, N. Hagiwara,
K. Kawata, T. Okeda, H. F. Wang, K. Fugami, M. Kosugi, Org. Lett.
2001, 3, 3313; c) C. G¸rtler, S. L. Buchwald, Chem. Eur. J. 1999, 5,
3107; d) C. G. Blettner, W. A. Kˆnig, W. Stenzel, T. Schotten,
10-b-Naphthyl-1-phenyl-9,10-dihydrophenanthrene (7 f): Reaction time
24 h. Eluent hexane/diethyl ether (4:1), 96% yield. M.p. 130 1310C;
1H NMR (300 MHz): d ˆ 7.94 (dd, J ˆ 1.0 and 8.0 Hz, 1H), 7.91 (d, J ˆ
8.0 Hz, 1H), 7.47 (t, J ˆ 7.7 Hz, 2H), 7.37 6.96 (m, 12H), 6.83 6.78 (m,
2H), 4.43 (dd, J ˆ 1.6 and 5.8 Hz, 1H), 3.43 (dd, J ˆ 5.8 and 15.0 Hz, 1H),
3.06 ppm (dd, J ˆ 1.6 and 15.0 Hz, 1H); 13CNMR (75 MHz): d ˆ 142.2,
141.4, 141.2, 135.9, 135.5, 135.1, 134.3, 133.3, 131.9, 129.8, 129.2, 128.8, 127.8,
127.7, 127.6, 127.4, 127.3, 127.1, 127.0, 126.6, 126.5, 125.5, 125.1, 123.8, 123.6,
ƒ
Tetrahedron Lett. 1999, 40, 2101; e) M. Moreno-Manas, R. Pleixats,
A. Roglans, Synlett 1997, 1157; f) S. Cacchi, P. G. Ciattini, E. Morena,
P. Pace, Synlett 1996, 545; g) A. Arcadi, S. Cacchi, G. Fabrizi, F.
Marinelli, P. Pace, Tetrahedron 1996, 52, 6983; h) A. Amorese, A.
Arcadi, E. Bernocchi, S. Cacchi, S. Cerrine, W. Fedeli, G. Ortar,
Tetrahedron 1989, 45, 813; i) S. Cacchi, P. G. Ciattini, E. Morera, G.
Ortar, Tetrahedron Lett. 1987, 28, 3039; j) L. S. Hegedus, P. J.
Harrington, J. Org. Chem. 1984, 49, 2657; k) F. Naso, O. Sciacovelli,
Tetrahedron Lett. 1983, 24, 4603; k) See also, ref. [31].
‡
40.7, 37.4 ppm; HRMS (FAB ‡ ): calcd for C30H22 ([M ]) 382.1721, found
382.1712.
General procedure for the preparation of the trisubstituted a,b-unsatu-
rated sulfones (25): A mixture of the corresponding a,b-unsaturated
sulfone 23 (0.4 mmol), silver carbonate (0.8 mmol, 200 mol%), Pd(OAc)2
(0.04 mmol, 10 mol%), phenyl iodide (1.2 mmol, 300 mol%), and DMF
(2 mL) was heated at 1200Cunder vigorous stirring and argon atmosphere
for 30 h. The mixture was allowed to cool to room temperature, diluted
with Et2O (20 mL), filtered through celite, washed with water (20 mL),
dried (MgSO4), and evaporated. The residue was purified by flash
chromatography to afford 25 (the eluent and yield are indicated below
for each case).
[5] For the synthesis of trisubstituted acyclic a,b-unsaturated sulfoxides
by Heck reaction, see: a) I. Alonso, J. C. Carretero, J. Org. Chem.
2001, 66, 4453; b) N. DÌaz Buezo, O. GarcÌa Manchenƒo, J. C. Carre-
tero, Org. Lett. 2000, 2, 1451.
[6] a) J. Adrio, M. RodrÌguez Rivero, J. C. Carretero, Angew. Chem. 2000,
112, 3028; Angew. Chem. Int. Ed. 2000, 39, 2906; b) J. de Vicente, R.
(E)-1-[2-(N,N-dimethylamino)phenylsulfonyl]-3-methyl-2-phenyl-1-bu-
tene (25a): Eluent hexane/ethyl acetate (10:1), 85% yield. 1H NMR
(200 MHz): d ˆ 8.13 (dd, J ˆ 1.6 and 7.8 Hz, 1H), 7.59 (m, 1H), 7.40 (dd, J ˆ
1.1 and 8.1 Hz, 1H), 7.36 7.27 (m, 5H), 7.18 7.09 (m, 1H), 6.47 (s, 1H),
3.77 (m, 1H), 2.76 (s, 6H), 0.85 ppm (d, J ˆ 7.0 Hz, 6H); 13CNMR
(50 MHz): d ˆ 161.5, 154.1, 139.5, 138.5, 134.2, 130.6, 129.1, 127.9, 127.8,
125.2, 123.7, 46.0, 29.1, 20.6 ppm; HRMS (FAB ‡ ): calcd for C19H24NO2S
¬
¬
Gomez Arrayas, J. Canƒada, J. C. Carretero, Synlett 2000, 53; c) J. C.
¬
¬
Carretero, R. Gomez Arrayas, Synlett 1999, 49; d) J. L. Garrido, I.
Alonso, J. C. Carretero, J. Org. Chem. 1998, 63, 9406; e) J. C.
Carretero, R. Gomez Arrayas, J. Org. Chem. 1998, 63, 2993.
[7] a) Z. Jin, P. L. Fuchs, Tetrahedron Lett. 1993, 34, 5205; b) S. W. Lee,
P. L. Fuchs, Tetrahedron Lett. 1993, 34, 5209.
¬
¬
¬
[8] Previous communication: P. Mauleon, I. Alonso, J. C. Carretero,
‡
([M ‡ H] ) 330.1528, found 330.1530.
Angew. Chem. 2001, 113, 1331; Angew. Chem. Int. Ed. 2001, 40, 1291.
[9] General references: a) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev.
2002, 102(5) 1731; b) C. Jia, T. Kitamura, Y. Fujiwara, Acc. Chem. Res.
2001, 34, 633; c) Activation ofUnreactive Bonds in Organic Synthesis
(Ed.: S. Murai), Springer, Berlin, 1999; d) E. Shilov, G. B. Shul'pin,
Chem. Rev. 1997, 97, 2879.
(E)-1-[2-(N,N-dimethylamino)phenylsulfonyl]-2-phenyl-1-heptene (25c):
Eluent hexane/ethyl acetate (15:1), 70% yield. 1H NMR (200 MHz): d ˆ
8.14 (dd, J ˆ 1.6 and 7.8 Hz, 1H), 7.55 (m, 1H), 7.42 7.27 (m, 7H), 6.81 (s,
1H), 2.84 (m, 4H), 2.74 (s, 6H), 1.05 (m, 4H), 0.73 ppm (m, 3H); 13CNMR
(75 MHz): d ˆ 155.8, 154.0, 139.7, 139.5, 134.2, 129.4, 129.2, 129.1, 128.7,
Chem. Eur. J. 2003, 9, No. 7
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0907-1519 $ 20.00+.50/0
1519

J. C. Carretero et al.
FULL PAPER
¬
[10] For leading references, see: a) M. Catellani, C. Mealli, E. Motti, P.
Matute, A. Monge, E. Gutierrez-Puebla, A. M. Echavarren, Organo-
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Dennison, J. K. Kodanko, L. E. Overman, Angew. Chem. 2001, 113,
1485; Angew. Chem. Int. Ed. 2001, 40, 1439; c) C. Mateo, C.
ƒ
Paoli, E. Perez-Carreno, P. S. Pregosin, J. Am. Chem. Soc. 2002, 124,
4336; b) M. Catellani, E. Motti, S. Baratta, Org. Lett. 2001, 3, 3611;
c) M. Catellani, E. Motti, L. Paterlini, J. Organomet. Chem. 2000, 593,
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Organomet. Chem. 1999, 580, 191; g) M. Catellani, E. Motti, New J.
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Albrecht, O. Reiser, M. Weber, B. Knieriem, A. de Meijere, Tetrahe-
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Jones, P. Bubenitschek, Angew. Chem. 1993, 105, 1805; Angew. Chem.
Int. Ed. Engl. 1993, 32, 1733.
¬
¬
Fernandez-Rivas, D. J. Cardenas, A. M. Echavarren, Organometallics
¬
¬
1998, 17, 3661; d) C. Mateo, D. J. Cardenas, C. Fernandez-Rivas, A. M.
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Cheng, Organometallics 1994, 13, 18.
[21] Review on organopalladium(iv) chemistry: A. J. Canty, Acc. Chem.
Res. 1992, 25, 83.
[22] For PdIV five-membered palladacycles, see for instance: a) M.
Catellani, G. P. Chiusoli, M. Costa, J. Organomet. Chem. 1995, 500,
69; b) G. Bocelli, M. Catellani, S. Ghelli, J. Organomet. Chem. 1993,
458, C12; c) M. Catellani, B. E. Mann, J. Organomet. Chem. 1990, 390,
251; d) see also reference [10]. For the isolation and X-ray structure of
an arylpalladium(iv) five-membered palladacycle, see: e) J. M. Bru-
nel, M.-H. Hirlemann, A. Heumann, G. Buono, Chem. Commun.
2000, 1869.
[23] For
a
mechanistic alternative avoiding PdIV intermediates, but
requiring ligand-exchange reactions between two PdII complexes,
see: G. Dyker, Chem. Ber. 1994, 127, 739.
[11] For some recent reviews on palladium-mediated domino reactions,
see: a) G. Poli, G. Giambastiani, A. Heumann, Tetrahedron 2000, 56,
5959; b) R. Grigg, V. Sridharan, J. Organomet. Chem. 1999, 576, 65;
c) A. de Meijere, S. Br‰se, J. Organomet. Chem. 1999, 576, 88.
[12] Carbon-substituted palladacycle intermediates are also assumed to be
[24] For the isolation of seven-membered palladacycles, see: A. S. K.
Hashmi, A. R. Nass, J. W. Bats, M. Bolte, Angew. Chem. 1999, 111,
3565; Angew. Chem. Int. Ed. 1999, 38, 3370.
[25] Unlike the reaction with p-iodotoluene, the reaction with o-iodoto-
luene and m-iodotoluene afforded complex mixtures of products.
[26] In the structural elucidation of compounds 17 and 18 the chemical
shifts and coupling constants of the aromatic protons of the
dihydrophenanthrene unit are particularly interesting. Compound 17
1H NMR (500 MHz, CDCl3): d ˆ 7.53 (d, J ˆ 8.1 Hz; H5), 7.20 (dd, J ˆ
1.8 and 8.1 Hz; H6), 6.96 (brs; H4), 6.92 ppm (brs, 1H; H2). Compound
18 1H NMR (500 MHz, CDCl3): d ˆ 8.19 (brs; H4), 8.15 (brd, J ˆ
8.4 Hz; H6), 7.95 (d, J ˆ 8.4 Hz; H5), 7.88 (brs; H2), 7.76 ppm (brs; H8).
[27] cis-1h was prepared by photochemical stereoselective iodosulfonyla-
tion of p-tolylacetylene (I2, NaPhSO2, hn) and reductive cleavage of
À
involved in other types of palladium-catalyzed C H activation
processes. For reviews, see: a) G. Dyker, Angew. Chem. 1999, 111,
1808; Angew. Chem. Int. Ed. 1999, 38, 1698; b) G. Dyker, Chem. Ber./
Recueil 1997, 130, 1567; c) M. Catellani, G. P. Chiusoli, Gazz. Chim.
Ital. 1993, 123, 1. For the application of palladacycles in Heck type
reactions, see: d) W. A. Herrmann, V. P. W. Bˆlm, C.-P. Reisinger, J.
Organomet. Chem. 1999, 576, 23; e) see also ref. [11c].
[13] The a,b-unsaturated sulfones 1 were readily prepared according to
well-established procedures (by condensation of a-sulfonyl carban-
ions with aldehydes and further dehydration or by Wadsworth Em-
mons olefination). For a review on synthesis of sulfones, see: a) N. S.
Simpkins, Sulphones in Organic Synthesis, Pergamon, Oxford, 1993.
See also: b) G. H. Posner, D. J. Brunelle, J. Org. Chem. 1972, 37, 3547.
[14] Allyl sulfones tend to be more thermodynamically stable than vinyl
sulfones (see, for example, ref. [13a], p. 39).
À
the C I bond (58% overall yield) following the procedure described
in the literature for the preparation of cis-1e: a) G. L. Edwards, C. A.
Muldoon, D. J. Sinclair, Tetrahedron 1996, 52, 7779; b) W. E. Truce, G.
CWolf, J. Org. Chem. 1971, 36, 1727.
[28] trans-Di(m-acetato)bis[ortho-(di-ortho-tolylphosphino)benzyl]dipal-
ladium(ii). For a recent reference, see: V. P. W. Bˆhm, W. A. Herr-
mann, Chem. Eur. J. 2001, 7, 4191, and references therein.
[15] Although smaller quantities of Ag2CO3 (100 mol%) and Pd(OAc)2
(2 mol%) can be used in the domino arylation of 1a, both the
conversion and the 4a:3a selectivity decreased significantly.
[29] Significant 1H NMR data of compound 19 (500 MHz, CDCl3): d ˆ 7.65
(brd, J ˆ 7.9 Hz ; H5), 7.38 (dt, J ˆ 2.0 and 6.9 Hz; H6), 7.22 (dt, J ˆ 0.9
and 7.3 Hz; H7), 6.95 ppm, (brs; H2). On the other hand, according to
the mechanistic proposal for the palladium-catalyzed arylation of cis-
substituted a,b-unsaturated phenyl sulfones (Scheme 9), both diaster-
eomeric alkenes trans-1e and cis-1e afforded the same C9/C10 trans
substituted dihydrophenanthrene 4e (82% and 68% yields, respec-
tively) in the reaction with PhI/Ag2CO3.
[16] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-151679 (for 4a), CCDC-151680 (for 4e), and CCDC-181908
(for 4 h). Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
(‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
[17] We have noticed a slow isomerization of 3b to allyl phenyl sulfone
even in a pure state at room temperature. In fact, to completely
suppress the formation of allyl phenyl sulfone, 3b must be kept in the
freezer once it has been purified by chromatography.
[18] Dihydrophenanthrenes 4 can be routinely obtained with purities of
88 97% after flash chromatography. In most cases complete
elimination of the minor Heck product was achieved by further
recrystallization from diethyl ether.
[30] The E stereochemistry of several trisubstituted olefins 3 and 25 was
unequivocally established by NOESY experiments.
[31] For a related coordination control in Heck reactions of 2-pyridyldi-
methylsilyl-substituted alkenes, see: a) K. Itami, T. Nokami, Y.
Ishimura, K. Mitsudo, T. Kamei, J.-I. Yoshida, J. Am. Chem. Soc.
2001, 123, 11577; b) K. Itami, T. Nokami, J.-I. Yoshida, J. Am. Chem.
Soc. 2001, 123, 5600; c) K. Itami, K. Mitsudo, T. Kamei, T. Koike, T.
À
Nokami, J.-I Yoshida,. J. Am. Chem. Soc. 2000, 122, 12013. For Pd N
[19] Very significant characterization data of the dihydrophenanthrenes 4
are the molecular peak determined by MS (FAB ionization) and the
chemical shifts of C9, C10, H9, and H10 in their 13Cand 1H NMR
spectra. On the other hand, in all cases the small value of J9,10 (1.1
1.9 Hz in CDCl3) is characteristic of the trans stereochemistry at C9/
C10. This feature is also supported by the dihedral angle value
determined by X-ray analysis of 4a and 4e (H9-C9-C10-H10 ˆ À61.20
for 4a and À69.70 for 4e).
coordinated complexes in Heck reaction of nitrogen-containing vinyl
ethers, see: d) P. Nilsson, M. Larhed, A. Hallberg, J. Am. Chem. Soc.
2001, 123, 8217; e) M. Larhed, C. Andersson, A. Hallberg, Tetrahe-
dron 1994, 50, 285; f) see also ref. [5].
[32] G. M. Sheldrick, University of Gˆttingen, Gˆttingen (Germany),
1998.
Received: May 10, 2002
Revised: November 29, 2002 [F4080]
[20] For the isolation of five-membered carbon substituted palladacycles,
¬
¬
see, for instance: a) C. Fernandez-Rivas, D. J. Cardenas, B. MartÌn-
1520
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