Oxidative Cross-Coupling of N-(2′-Phenylphenyl)benzene-sulfonamides or Benzoic and Naphthoic Acids with Alkenes Using a Palladium-Copper Catalyst System under Air

Article abstract of DOI:10.1021/jo980584b

N-(2′-Phenylphenyl)benzenesulfonamides react with acrylate esters accompanied via cleavage of the C-H bond at their 2′-position in the presence of a catalyst system of Pd(OAc)₂ and Cu(OAc)₂ and a base under air to produce 5,6-dihydro-5-(benzenesulfonyl)phenanthridine-6-acetate derivatives in high yields. The reactions of benzoic acid with butyl acrylate and styrene can also give 3-[(butoxycarbonyl)methyl]phthalide and 3-phenylisocoumarin, respectively.

Full text of DOI:10.1021/jo980584b

J . Org. Chem. 1998, 63, 5211-5215
5211
Oxid a tive Cr oss-Cou p lin g of N-(2′-P h en ylp h en yl)ben zen e-
su lfon a m id es or Ben zoic a n d Na p h th oic Acid s w ith Alk en es Usin g
a P a lla d iu m -Cop p er Ca ta lyst System u n d er Air
Masahiro Miura,* Takatoshi Tsuda, Tetsuya Satoh, Sommai Pivsa-Art, and
Masakatsu Nomura
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, J apan
Received March 30, 1998
N-(2′-Phenylphenyl)benzenesulfonamides react with acrylate esters accompanied via cleavage of
the C-H bond at their 2′-position in the presence of a catalyst system of Pd(OAc)2 and Cu(OAc)2
and a base under air to produce 5,6-dihydro-5-(benzenesulfonyl)phenanthridine-6-acetate derivatives
in high yields. The reactions of benzoic acid with butyl acrylate and styrene can also give
3-[(butoxycarbonyl)methyl]phthalide and 3-phenylisocoumarin, respectively.
In tr od u ction
conditions similar to those for the Heck- and Wacker-
type reactions to give 2-(2′-arylphenyl)phenols4h and
6-substituted 6H-dibenzo[b,d]pyran derivatives,4i respec-
tively. Both the reactions apparently involve the regio-
selective cleavage of the C-H bond at the 2′-position of
the substrates, and the phenolic function appears to act
as an effective ligating group for its promotion. For the
development of these new palladium-catalyzed reactions,
it seems to be very crucial to find effective functional
groups other than phenolic function. Therefore, we
examined the oxidative coupling with alkenes employing
The activation of C-H bonds in organic compounds by
transition-metal complexes is currently one of the most
significant subjects in both organic and organometallic
chemistry. An effective strategy to regioselectively ac-
tivate the aromatic C-H bond by transition-metal com-
plexes has been known to introduce a functional group
having ligating ability at an appropriate position of a
given aromatic substrate.1 Recently, a number of cata-
lytic coupling reactions of aromatic compounds bearing
carbonyl or nitrogen-containing groups with alkenes and/
or alkynes involving such a C-H bond activation mode
as the key step have also been successfully developed,
especially by using ruthenium and rhodium complexes.2,3
Meanwhile, in our study of palladium-catalyzed reactions
using phenolic compounds as substrates,4 we observed
that 2-phenylphenols could catalytically react with aryl
iodides and alkenes such as acrylate esters under the
a
number of N-containing substrates, including
N-benzylideneaniline,3d 2-phenylpyridine,3c,f and 2-phen-
ylaniline, which are known to readily undergo stoichio-
metric orthopalladation by treatment with palladium(II)
species,5 in the presence of Pd(OAc)2 and Cu(OAc)2 under
air.4i While none of them could be used, it was found
that the N-(arylsulfonyl) derivatives of the third com-
pound, which are rather acidic, very efficiently react with
acrylate esters by adding an appropriate base to give 5,6-
dihydro-5-(benzenesulfonyl)phenanthridine-6-acetate de-
rivatives (eq 1). Furthermore, structurally related acidic
compounds, benzoic and naphthoic acids, were observed
to be capable of reacting with acrylate esters and
styrene.6,7 These findings are reported herein.
(1) For reviews, see: (a) Newkome, G. R.; Puckett, W. E.; Gupta, V.
K.; Kiefer, G. E. Chem. Rev. 1986, 86, 451. (b) Ryabov, A. D. Chem.
Rev. 1990, 90, 403.
(2) Carbonyl-directed catalytic reactions: (a) Murai, S.; Kakiuchi,
F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N.
Nature (London) 1993, 366, 529. (b) Murai, S. J . Synth. Org. Chem.
J pn. 1994, 54, 992. (c) Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani,
A.; Sonoda, M.; Chatani, N.; Murai, S. Bull. Chem. Soc. J pn. 1995,
68, 62. (d) Kakiuchi, F.; Tanaka, Y.; Sato, T.; Chatani, N.; Murai, S.
Chem. Lett. 1995, 679. (e) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.;
Murai, S. Chem. Lett. 1995, 681. (f) Sonoda, M.; Kakiuchi, F.;
Kamatani, A.; Chatani, N.; Murai, S. Chem. Lett. 1996, 109. (g) Trost,
B. M.; Imi, K. Davies, I. W. J . Am. Chem. Soc. 1995, 117, 5371.
(3) Nitrogen-directed catalytic reactions: (a) Moore, E. J .; Pretzer,
W. R.; O’Connell, T. J .; Harris, J .; LaBounty, L.; Chou, L.; Grimmer,
S. S. J . Am. Chem. Soc. 1992, 114, 5888. (b) Aulwurm, U. R.;
Melchinger, J . U.; Kisch, H. Organometallics 1995, 14, 3385. (c) Lim,
Y.-G.; Kang, J .-B.; Kim, Y. H. J . Chem. Soc., Perkin Trans. 1 1996,
2201. (d) Kakiuchi, F.; Yamauchi, M.; Chatani, N.; Murai, S. Chem.
Lett. 1996, 111. (e) Chatani, N.; Fukuyama, T.; Kakiuchi, F.; Murai,
S. J . Am. Chem. Soc. 1996, 118, 493. (f) Chatani, N.; Ie, Y.; Kakiuchi,
F.; Murai, S. J . Org. Chem. 1997, 62, 2604.
(4) (a) Itoh, K.; Miura, M.; Nomura, M. Tetrahedron Lett. 1992, 33,
5369. (b) Satoh, T.; Kokubo, K.; Miura, M.; Nomura, M. Organome-
tallics 1994, 13, 4431. (c) Satoh, T.; Ikeda, M.; Miura, M.; Nomura, M.
J . Mol. Catal. A: Chem. 1996, 111, 25. (d) Satoh, T.; Tsuda, T.;
Kushino, Y.; Miura, M.; Nomura, M. J . Org. Chem. 1996, 61, 6476. (e)
Satoh, T.; Itaya, T.; Miura, M.; Nomura, M. Chem. Lett. 1996, 823. (f)
Satoh, T.; Ikeda, M.; Kushino, Y.; Miura, M.; Nomura, M. J . Org. Chem.
1997, 62, 2662. (g) Satoh, T.; Ikeda, M.; Miura, M.; Nomura, M. J .
Org. Chem. 1997, 62, 4877. (h) Satoh, T.; Kawamura, Y.; Miura, M.;
Nomura, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 1740. (i) Miura,
M.; Tsuda, Satoh, T.; T.; Nomura, M. Chem. Lett. 1997, 1103.
S0022-3263(98)00584-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/03/1998

5212 J . Org. Chem., Vol. 63, No. 15, 1998
Miura et al.
Ta ble 1. Rea ction of
N-(2′-P h en ylp h en yl)-4-ch lor oben zen esu lfon a m id e (1a )
w ith Eth yl Acr yla te (2a )a
Ta ble 2. Rea ction of
N-(2′-P h en ylp h en yl)ben zen esu lfon a m id es 1 w ith
Alk en es 2a
entry
base
none
NaOAc
KOAc
Na2CO3
NaOAc
time/h
yield of 3b/%
1
2
3
27
9
14
9
33
92 (91)
92
4
91
57
5c
48
a
Reaction conditions: 1a (1 mmol), 2a (3 mmol), Pd(OAc)2 (0.05
mmol), Cu(OAc)2‚H2O (0.05 mmol), base (0.5 mmol), MS 4A (400
b
mg), in DMF (5 mL) under air (1 atm). GLC yield based on
amount of 1a used. Value in parentheses indicates isolated yield.
c Without Cu(OAc)2‚H2O.
Resu lts a n d Discu ssion
When a mixture of N-(2′-phenylphenyl)-4-chloroben-
zenesulfonamide (1a , X ) Cl, Y ) H) (1 mmol) and ethyl
acrylate (2a ) (3 mmol) was stirred in the presence of Pd-
(OAc)2 (0.05 mmol), Cu(OAc)2‚H2O (0.05 mmol), and
molecular sieves (MS 4A) (400 mg) in DMF (5 mL) under
air (1 atm) at 100 °C for 27 h, ethyl 5,6-dihydro-5-[(4′-
chlorophenyl)sulfonyl]phenanthridine-6-acetate (3) was
formed in a yield of 33% (entry 1 in Table 1). The
structure of 3 was unambiguously determined by its 2D-
NMR spectra (H,H- and C,H-COSY) and NOE experi-
ments (see the Experimental Section). Addition of an
inorganic base was found to significantly enhance the
reaction. Thus, product 3a was obtained in 92% yield in
the presence of NaOAc within 9 h (Table 1, entry 2).8
Other bases, KOAc and Na2CO3, could also be used as
well as NaOAc (Table 1, entries 3 and 4). While the
reaction took place in the absence of Cu(OAc)2, it was
rather sluggish (Table 1, entry 5).9
Table 2 summarizes the results for the reaction of 1a
with alkenes 2b-f and N-(2′-phenylphenyl)benzene-
sulfonamide (1b), N-(2′-phenylphenyl)-4-methylbenzene-
sulfonamide (1c), or N-(2′-phenyl-4′-bromophenyl)-4-
methylbenzenesulfonamide (1d ) with 2a . When acrylate
esters 2b-d and amide 2e were used in place of 2a , the
corresponding 5,6-dihydrophenanthridine-6-acetic acid
derivatives 4-7 were produced in excellent yields, as was
3. The reaction with acrylonitrile (2f) also gave the
corresponding product 8. However, styrene (2g) did not
react with 1a . Substituents on the benzenesulfonyl
moiety were found to considerably affect the reactivity
of 1. The reactivity order of 1a -c judged from the
a
Reaction conditions: 1 (1 mmol), 2 (3 mmol), Pd(OAc)2 (0.05
mmol), Cu(OAc)2‚H2O (0.05 mmol), NaOAc (0.5 mmol), MS 4A (400
mg) in DMF (5 mL) under air (1 atm). GLC yield based on
b
amount of 1 used. Value in parentheses indicates isolated yield.
c KOAc (0.5 mmol) was used in place of NaOAc.
Sch em e 1
reaction progress under the same conditions using NaOAc
as base followed the sequence 1a (X ) Cl) > 1b (X ) H)
> 1c (X ) Me), suggesting that an electron-withdrawing
group in X may enhance the reaction. Consistent with
this, 1d appeared to be more reactive than 1c. It should
be noted that in the case of 1c the use of KOAc in place
of NaOAc significantly improved the reaction efficiency,
giving product 10 in a yield of 90%.
(5) (a) Canty, A. J . In Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford,
1995; Vol. 9, Chapter 5, p 225. (b) Tsuji, J . Palladium Reagents and
Catalysts; Wiley: Chichester, 1995; pp 87-94.
(6) Preliminary attempts of coupling of the sulfonamides or acids
with aryl iodides have not yet succeeded.
It may be reasonable to consider that the present
coupling involves initial orthopalladation by the reaction
of 1 with Pd(II) species and the subsequent reaction with
2 followed by intramolecular nucleophilic cyclization
produces the dihydrophenanthridines (Scheme 1). Pd(0)
species formed may be reoxidized by the added copper
species and air.10 The initial step may take place after
the coordination of 1 to Pd(II) species accompanied by
(7) Palladium-catalyzed reaction of aromatic compounds with alk-
enes, which does not involve orthopalladation: Fujiwara, Y.; J intoku,
T.; Takaki, K. CHEMTECH 1990, 636. Reference 5b, pp 55-59.
(8) Predrying of the base was found to be important (see the
Experimental Section); without this process and/or in the absence of
MS 4A, the yield of 3a was reduced to 77-84%. In the reaction of acid
13 with 2b without using MS 4A, the product yield was less than 10%.
Thus, MS 4A as desiccant was always used.
(9) In this case, air itself may directly act as an oxidant: Satoh, T.;
Miura, M.; Nomura, M. J . Mol. Catal. A: Chem. 1996, 112, 211.

Cross-Coupling of N-(2′-Phenylphenyl)benzenesulfonamides
J . Org. Chem., Vol. 63, No. 15, 1998 5213
Ta ble 3. Rea ction of Ar om a tic Ca r boxylic Acid s w ith
Bu tyl Acr yla te (2b) or Styr en e (2g)a
deprotonation, which seems to be enhanced by base. The
observed substituent electronic effect is attributable to
the perturbation of acidity of 1; a small change in the
acidity appears to significantly affect the reaction ef-
ficiency, an electron-withdrawing group in X or Y en-
hancing the deprotonation step. The result that KOAc
was significantly more effective than NaOAc in the
reaction of 1c may be attributed to the fact that potas-
sium carboxylate is relatively more effective as base as
well as nucleophile than the corresponding sodium salt
in DMF.11
In contrast to the good efficiency of sulfonamides 1 for
the oxidative coupling with alkenes, the reaction of
2-phenylaniline itself as well as N-benzylideneaniline and
2-phenylpyridine with 2a did not proceed, although the
aniline is known to react with Pd(OAc)2 stoichiometrically
to produce the corresponding orthopalladated complex as
mentioned above.12 These facts suggest that the rela-
tively acidic nature of N-H proton in 1 as well as O-H
proton in 2-phenylphenols seems to be one of crucial
factors making the catalytic coupling effective.13 It was
confirmed that treatment of less acidic substrates, N-
acetyl- and N-(trifluoroacetyl)-2-phenylanilines, with 2a
gave no expected products, whereas that of N-(methyl-
sulfonyl)-2-phenylaniline did afford compound 12 (eq 2).
The reaction of N-(1-naphthyl)-4-chlorobenzenesulfona-
mide with 2a , however, did not occur.4h
a
Reaction conditions: ArCOOH (1 mmol), 2 (3 mmol), Pd(OAc)2
(0.1 mmol), Cu(OAc)2‚H2O (0.1 mmol), MS 4A (400 mg) in DMF
b
(5 mL) under N2-air (5:1, 900 mL). GLC yield based on amount
of ArCOOH used. Value in parentheses indicates isolated yield.
d
c Pd(OAc)2 (0.05 mmol) was used. Cu(OAc)2‚H2O (0.05 mmol) was
used.
give either phthalide and/or isocoumarin derivatives.14
Thus, this reaction sequence appears to be mechanisti-
cally relevant to the present oxidative coupling, while its
initial stage seems to involve direct orthopalladation, Tl-
(OCOCF3)3 being replaced by a catalytic amount of Cu-
(OAc)2 and air. The formation of isocoumarin 19 in the
present system is of particular interest, since two differ-
ent oxidative catalytic cycles are considered to partici-
pate, four hydrogens being eliminated during the cou-
pling. Consequently, a number of aromatic acids 14-
17 were also subjected to the reaction with 2g (Table 3).
It was of considerable interest that the reaction of
2-methylbenzoic acid (15) and 1-naphthoic acid (16)
selectively produced benzylidenephthalides 22 and 23,
whereas that of 2-naphthoic acid (17) afforded isocou-
marin 24. The reaction of 4-methoxybenzoic acid (14)
gave a mixture of isocoumarin 20 and benzylideneph-
thalide 21.
The above information obtained in the reaction of
sulfonamides prompted us to investigate applicability of
aromatic carboxylic acids for the coupling; the functional
group may be regarded as a structural relative of sul-
fonamide, while it is considerably more acidic than the
amide. It was found that benzoic acid (13) can react with
2b to give 3-(butoxycarbonyl)methylphthalide (18) in 50%
yield as the single major product (Table 3). In this case,
no positive result was obtained by addition of NaOAc.
From the reaction of 13 with styrene (2g) was obtained
3-phenylisocoumarin (19).
It is noted that benzoic acid is known to undergo
orthothallation on treatment with a stoichiometric amount
of Tl(OCOCF3)3, and the thallated species reacts with
alkenes in the presence of a catalytic amount of PdCl2 to
Scheme 2 illustrates possible paths leading to phthal-
ides and isocoumarins, which involve ortho-vinylation
and nucleophilic cyclization or Wacker-type oxidative
cyclization.14 The observed structures of products from
the reactions using styrene may imply that both the
regiochemistry of initial orthopalladation and the mode
of oxidative cyclization are sterically controlled. The fact
(10) There would be also a possibility that
participates in the reaction: Hosokawa, T.; Murahashi, S.-I. Acc. Chem.
Res. 1990, 23, 49.
a Pd-Cu complex
(11) Dijkstra, G.; Kruizinga, W. H.; Kellogg, R. M. J . Org. Chem.
1987, 52, 4230.
(12) See, for example: Albert, J .; Granell, J .; Luque, A.; M´ınguez,
J .; Moragas, R.; Font-Bardı´a, M.; Solans, X. J . Organomet. Chem. 1996,
522, 87.
(13) Wolfe, J . P.; Rennels, R. A.; Buchwald, S. L. Tetrahedron 1996,
52, 7525 and references therein.
(14) Larock, R. C.; Varaprath, S.; Lau, H. H.; Fellows, C. A. J . Am.
Chem. Soc. 1984, 106, 5274.

5214 J . Org. Chem., Vol. 63, No. 15, 1998
Miura et al.
air (1 atm) at 100-120 °C for 5-39 h. After cooling, the
reaction mixture was extracted with diethyl ether and dried
over sodium sulfate. Product was isolated by column chro-
matography on silica gel using hexanes-ethyl acetate as
eluent.
Sch em e 2
Eth yl 5,6-dih ydr o-5-[(4′-ch lor oph en yl)su lfon yl]ph en an -
th r id in e-6-a ceta te (3): mp 106.5-107 °C; 1H NMR δ 1.28 (t,
3H, J ) 6.8 Hz, CH3), 2.42 (dd, 1H, J ) 7.3, 15.1 Hz, Ha), 2.55
(dd, 1H, J ) 8.3, 15.1 Hz, Ha), 4.18 (dq, 2H, J ) 1.5, 6.8 Hz,
CH2O), 5.79 (dd, 1H, J ) 7.3, 8.3 Hz, H6), 6.86 (d, 2H, J ) 8.8
Hz, H2′), 6.93 (d, 2H, ) 8.8 Hz, H1′), 7.16-7.19 (m, 3H, H,7 H,8
H9), 7.25-7.28 (m, 1H, H10), 7.38 (dt, 1H, J ) 1.5, 7.3 Hz, H3),
7.43 (dt, 1H, J ) 1.5, 7.3 Hz, H2), 7.60 (dd, 1H, J ) 2.0, 7.8
Hz, H1), 7.77 (dd, 1H, J ) 1.5, 7.8 Hz, H4); 13C NMR δ 14.22,
40.19, 55.86, 60.94, 123.47, 123.67, 126.72, 127.88, 128.02,
128.08, 128.21, 128.37, 128.86, 129.45, 129.58, 129.81, 132.50,
133.55, 135.17, 138.76, 169.50; HRMS m/z (M+) calcd for
C23H20ClNO4S 441.0818, found 441.0819. Anal. Calcd for
C
23H20ClNO4S: C, 62.51; H, 4.56; N, 3.17. Found: C, 62.39;
H, 4.66; N, 3.17. The observed NOE peak enhancements were
as follows:
that the initial vinylation of 17 exclusively takes place
at the 3-position may be due to the presence of the
hydrogen at the 8-position. The selective formation of
benzylidenephthalides 22 and 23 from 15 and 16 may
also be attributed to the presence of the o-methyl group
and peri-hydrogen, respectively; steric repulsion between
them and the carbonyl oxygen seems to be smaller in
phthalide-type intermediates. In the case of 13 and 17,
such a repulsion is not involved, and hence, six-membered-
cyclization, which may be energetically favorable, pre-
dominantly occurs, giving 19 and 24. The formation of
isocoumarin 20 and phthalide 21 in comparable yields
from 14 suggests that another factor also intervenes. The
detail is, however, unclear at the present stage.
n -Bu t yl 5,6-d ih yd r o-5-[(4′-ch lor op h en yl)su lfon yl]-
p h en a n th r id in e-6-a ceta te (4): mp 54.5-55.5 °C; H NMR
1
δ 0.93 (t, 3H, J ) 7.3 Hz), 1.36 (tq, 2H, J ) 7.3, 7.3 Hz), 1.56-
1.65 (m, 2H), 242 (dd, 1H, J ) 6.8, 15.1 Hz), 2.56 (dd, 1H, J )
7.8, 15.1 Hz), 4.07-4.14 (m, 2H), 5.79 (dd, 1H, J ) 7.3, 8.3
Hz), 6.84 (d, 2H, J ) 8.8 Hz), 6.92 (d, 2H, J ) 8.8 Hz), 7.16-
7.18 (m, 3H), 7.25-7.27 (m, 1H), 7.37 (dd, 1H, J ) 1.5, 7.3
Hz), 7.42 (dt, 1H, J ) 1.5, 7.3 Hz), 7.60 (dd, 1H, J ) 2.0, 7.8
Hz), 7.76 (dd, 1H, J ) 1.5, 7.8 Hz); HRMS m/z (M+) calcd for
C
C
25H24NClO4S 470.1131, found 470.1198. Anal. Calcd for
25H24NClO4S: C, 63.89; H, 5.15; N, 2.98. Found: C, 63.96;
H, 5.20; N, 2.97.
In summary, we have described herein that N-(2′-
phenylphenyl)benzenesulfonamides or benzoic and naph-
thoic acids efficiently react with alkenes such as acrylate
esters via cleavage of an aromatic C-H bond under
palladium catalysis, which may provide convenient routes
to prepare some nitrogen- and oxygen-containing het-
erocyclic compounds.
Isob u t yl 5,6-d ih yd r o-5-[(4′-ch lor op h en yl)su lfon yl]-
p h en a n th r id in e-6-a ceta te (5): mp 78.0-79.0 °C; H NMR
1
δ 0.91 (dd, 6H, J ) 1.5, 6.8 Hz), 1.92 (qq, 1H, J ) 6.8, 6.8 Hz),
2.43 (dd, 1H, J ) 6.8, 15.1 Hz), 2.59 (dd, 1H, J ) 7.8, 15.1
Hz), 3.89 (dd, 2H, J ) 6.8, 8.8 Hz), 5.79 (t, 1H, J ) 7.8 Hz),
6.83 (d, 2H, J ) 8.8 Hz), 6.93 (d, 2H, J ) 8.8 Hz), 7.16-7.19
(m, 3H), 7.25-7.27 (m, 1H), 7.38 (dt, 1H, J ) 1.5, 7.8 Hz), 7.42
(dt, 1H, J ) 2.0, 7.3 Hz), 7.60 (dd, 1H, J ) 2.0, 7.3 Hz), 7.77
(dd, 1H, J ) 1.5, 7.8 Hz); HRMS m/z (M+) calcd for C25H24
NClO4S 470.1131, found 470.1199. Anal. Calcd for C25H24
-
-
Exp er im en ta l Section
NClO4S: C, 63.89; H, 5.15; N, 2.98. Found: C, 63.65; H, 5.05;
N, 2.93.
1H NMR spectra were recorded at 400 or 600 MHz in CDCl3
as solvent. MS data were obtained by EI, unless otherwise
noted. GLC analysis was carried out using a silicon OV-17
column (i.d. 2.6 mm × 1.5 m) or with a CBP-1 capillary column
(i.d. 0.5 mm × 25 m).
ter t-Bu t yl 5,6-d ih yd r o-5-[(4′-ch lor op h en yl)su lfon yl]-
p h en a n th r id in e-6-a ceta te (6): mp 125.5-126.5 °C; 1H NMR
δ 1.51 (s, 9H), 2.37 (d, 2H, J ) 7.8 Hz), 5.74 (dd, 1H, J ) 7.3,
8.3 Hz), 6.83 (d, 2H, J ) 8.8 Hz), 6.91 (d, 2H, J ) 8.8 Hz),
7.15-7.18 (m, 3H), 7.24-7.25 (m, 1H), 7.37 (dt, 1H, J ) 1.5,
7.3 Hz), 7.42 (dt, 1H, J ) 1.5, 7.3 Hz), 7.59 (dd, 1H, J ) 1.5,
7.3 Hz), 7.76 (d, 1H, J ) 7.3 Hz); HRMS m/z (M+) calcd for
25H24ClNO4S 469.9819, found 470.1213. Anal. Calcd for
25H24ClNO4S: C, 63.89; H, 5.15; N, 2.98. Found: C, 63.51;
H, 5.08; N, 2.96.
N,N-Dim eth yl-5,6-dih ydr o-5-[(4′-ch lor oph en yl)su lfon yl]-
p h en a n th r id in e-6-a ceta m id e (7): mp 194-195 °C; 1H NMR
δ 2.42 (dd, 1H, J ) 8.3, 15.1 Hz), 2.62 (s, 3H), 2.68 (1H, dd, J
) 5.9, 15.1 Hz), 2.88 (s, 3H), 5.91 (dd, 1H, J ) 5.9, 8.3 Hz),
7.15-7.18 (m, 2H), 7.25-7.31 (m, 2H), 7.38 (dt, 2H, J ) 1.5,
7.3 Hz), 7.42 (dt, 1H, J ) 1.5, 7.3 Hz), 7.62 (dd, 1H, J ) 2.0,
7.3 Hz), 7.80 (dd, 1H, J ) 1.0, 7.3 Hz); HRMS CI m/z ([M +
H]+) calcd for C23H22ClN2O3S 441.1056, found 441.1021. Anal.
Calcd for C23H21ClN2O3S: C, 62.65; H, 4.80; N, 6.35. Found:
C, 62.60; H, 4.76; N, 6.05.
N-Aryl and -(methylsulfonyl)-2-phenylanilines and N-(1-
naphthyl)-4-chlorobenzenesulfonamide were prepared by treat-
ment of 2-phenylaniline or 1-aminonaphthalene with the
corresponding sulfonyl chlorides or acetyl chloride in pyridine.
Sulfonamide 1d was prepared from 1c according to the
published procedure.15 Other starting materials were com-
mercially available. Solvents were purified by standard
methods before use.
C
C
Rea ction of Ben zen esu lfon a m id es w ith Alk en es. In
a 100-mL two-necked flask was placed NaOAc (41 mg, 0.5
mmol), which was then dried at 150 °C in vacuo for 2 h. Then,
Pd(OAc)2 (11.2 mg, 0.05 mmol), Cu(OAc)2‚H2O (10.0 mg, 0.05
mmol), 1 (1 mmol), 2 (3 mmol), MS 4A (400 mg), and DMF (5
mL) were added, and the resulting mixture was stirred under
(15) Bell, F. J . Chem. Soc. 1928, 2770.

Cross-Coupling of N-(2′-Phenylphenyl)benzenesulfonamides
J . Org. Chem., Vol. 63, No. 15, 1998 5215
5,6-Dih yd r o-5-[(4′-ch lor op h en yl)su lfon yl]p h en a n th r i-
d in e-6-a ceton itr ile (8): mp 171.5-172.5 °C; 1H NMR δ 2.49
(dd, 1H, J ) 7.8, 16.6 Hz), 2.64 (dd, 1H, J ) 7.3, 16.6 Hz),
5.61 (t, 1H, J ) 7.8 Hz), 6.88 (d, 2H, J ) 8.8 Hz), 6.94 (d, 2H,
J ) 8.8 Hz), 7.20-7.34 (m, 4H), 7.42 (dt, 1H, J ) 1.5, 7.3 Hz),
7.47 (dt, 1H, J ) 1.5, 7.3 Hz), 7.64 (dd, 1H, J ) 2.0, 7.8 Hz),
7.84 (dd, 1H, J ) 1.5, 7.8 Hz); 13C NMR δ 23.85, 55.27, 115.94,
123.62, 123.90, 127.02, 128.08, 128.33, 128.47, 128.52, 129.12,
129.15, 129.18, 129.27, 129.47, 131.19, 131.42, 134.64, 139.22;
3-P h en ylisocou m a r in (19): mp 84-85 °C (lit.14 mp 87-
88 °C); 1H NMR δ 6.95 (s, 1H), 7.40-7.51 (m, 5H), 7.72 (t, 1H,
J ) 7.3 Hz), 7.88 (dt, 2H, J ) 1.5, 8.1 Hz), 8.31 (d, 1H, J ) 8.0
Hz); 13C NMR δ 101.78, 120.55, 125.24, 125.95, 128.13, 128.81,
129.65, 129.95, 131.96, 134.83, 137.50, 153.63, 162.28; HRMS
m/z (M+) calcd for C15H10O2 222.0681, found 222.0662.
6-Meth oxy-3-p h en ylisocou m a r in (20):16 mp 136.5-137
1
°C; H NMR δ 3.93 (s, 3H), 6.88 (d, 1H, J ) 2.4 Hz), 6.89 (s,
1H), 7.03 (dd, 1H, J ) 2.4, 8.8 Hz), 7.42-7.48 (m, 3H), 7.83
(dd, 2H, J ) 1.5, 8.5 Hz), 8.23 (d, 1H, J ) 8.8 Hz); HRMS m/z
(M+) calcd for C16H12O3 252.0786, found 252.0786.
MS CI m/z 395, 397 ([M + H]+). Anal. Calcd for C21H15
-
ClN2O2S: C, 63.88; H, 3.83; N, 7.09. Found: C, 63.63; H, 3.81;
N, 7.02.
(Z)-3-Ben zylid en e-5-m eth oxyp h th a lid e (21): mp 137.5-
1
138 °C; H NMR δ 3.95 (s, 3H, CH3O), 6.36 (s, 1H, Ha), 7.05
Eth yl 5,6-d ih yd r o-5-(p h en ylsu lfon yl)p h en a n th r id in e-
6-a ceta te (9): mp 117.5-118.0 °C; 1H NMR δ 1.29 (t, 3H, J )
6.8 Hz), 2.42 (dd, 1H, J ) 6.8, 15.1 Hz), 2.55 (dd, 1H, J ) 8.3,
15.1 Hz), 4.18 (dq, 2H, J ) 2.4, 6.8 Hz), 5.82 (t, 1H, J ) 7.8
Hz), 6.90 (t, 2H, J ) 7.8 Hz), 7.04-7.18 (m, 6H), 7.24 (d, 1H,
J ) 7.3 Hz), 7.35 (dt, 1H, J ) 1.0, 7.3 Hz), 7.42 (dt, 1H, J )
1.5, 7.3 Hz), 7.58 (dd, 1H, J ) 1.5, 7.8 Hz), 7.79 (dd, 1H, J )
1.0, 7.8 Hz); HRMS m/z (M+) calcd for C23H21NO4S 407.1208,
found 407.1204. Anal. Calcd for C23H21NO4S: C, 67.80; H,
5.19; N, 3.44. Found: C, 67.75; H, 5.21; N, 3.41.
Eth yl 5,6-dih ydr o-5-[(4′-m eth ylph en yl)su lfon yl]ph en an -
th r id in e-6-a ceta te (10): mp 103.0-104.0 °C; 1H NMR δ 1.28
(t, 3H, J ) 6.8 Hz), 2.14 (s, 3H), 2.42 (dd, 1H, J ) 7.3, 15.1
Hz), 2.55 (dd, 1H, J ) 8.3, 15.1 Hz), 4.17 (dq, 2H, J ) 2.4, 6.8
Hz), 5.80 (dd, 1H, J ) 7.3, 8.3 Hz), 6.67 (d, 2H, J ) 8.3 Hz),
6.91(d, 2H, J ) 8.3 Hz), 7.08-7.17 (m, 3H), 7.23-7.25 (m, 1H),
7.34 (dt, 1H, J ) 1.5, 7.8 Hz), 7.40 (dt, 1H, J ) 2.0, 7.8 Hz),
7.58 (dd, 1H, J ) 2.0, 7.8 Hz), 7.78 (dd, 1H, J ) 1.5, 7.8 Hz);
MS m/z 421 (M+). Anal. Calcd for C24H23NO4S: C, 68.39; H,
5.50; N, 3.32; S, 7.61. Found: C, 68.18; H, 5.56; N, 3.28; S,
7.53.
(dd, 1H, J ) 7.3 Hz, H6), 7.14 (d, 1H, J ) 2.4 Hz, H4), 7.31 (t,
1H, J ) 7.3 Hz, H4′), 7.40 (t, 2H, J ) 7.3 Hz, H3′), 7.80-7.84
(m, 3H, H,7 H2′); 13C NMR δ 55.91, 102.68, 106.74, 116.06,
118.18, 127.01, 128.33, 128.72, 130.07, 133.10, 143.17, 144.50,
165.08, 166.70; HRMS m/z (M+) calcd for C16H12O3 252.0786,
found 252.0780. Anal. Calcd for C16H12O3: C, 76.18; H, 4.79.
Found: C, 76.28; H, 5.07.
(Z)-3-Ben zylid en e-7-m eth ylp h th a lid e (22):17 mp 158-
158.5 °C; 1H NMR δ 2.72 (s, 3H, CH3), 6.38 (s, 1H, Ha), 7.28-
7.33 (m, 2H, H,6 H4′), 7.41 (dt, 2H, J ) 1.5, 7.3 Hz, H3′), 7.55-
7.58 (m, 2H, H,4 H5), 7.84-7.86 (m, 2H, H2′); HRMS m/z (M+)
calcd for C16H12O2 236.0837, found 236.0845. Anal. Calcd for
C
16H12O2: C, 81.34; H, 5.12. Found: C, 81.05; H, 5.14. The
observed NOE peak enhancements in 21 and 22 were as
follows:
Eth yl 2-br om o-5,6-d ih yd r o-5-[(4′-m eth ylp h en yl)su lfo-
n yl]p h en a n th r id in e-6-a ceta te (11): mp 154.5-155.5 °C; 1H
NMR δ 1.28 (t, 3H, J ) 7.3 Hz), 2.15 (s, 3H), 2.41 (dt, 1H, J )
6.8, 14.6 Hz), 2.52 (dt, 1H, J ) 8.3, 14.6 Hz), 4.17 (dq, 2H, J
) 2.0, 7.3 Hz), 5.79 (dd, 1H, J ) 6.8, 7.3 Hz), 6.71 (d, 2H, J )
7.8 Hz), 6.94 (d, 2H, J ) 6.8 Hz), 7.11-7.21 (m, 4H), 7.52 (dd,
1H, J ) 2.0, 8.3 Hz), 7.66 (d, 1H, J ) 8.3 Hz), 7.72 (s, 1H); 13
C
NMR δ 14.21, 21.25, 40.37, 55.63, 60.94, 121.33, 123.35,
126.55, 126.7, 126.99, 127.97, 128.33, 128.50, 128.56, 131.08,
131.52, 131.55, 131.99, 133.90, 133.93, 143.20, 169.41; HRMS
m/z (M+) calcd for C24H22BrNO4S 499.0470, found 499.0468.
Anal. Calcd for C24H22BrNO4S: C, 57.61; H, 4.43; N, 2.80.
Found: C, 57.69; H, 4.41; N, 2.80.
Eth yl 5,6-d ih yd r o-5-(m eth ylsu lfon yl)p h en a n th r id in e-
6-a ceta te (12): mp 108.0-109.0 °C; 1H NMR δ 1.26 (t, 3H, J
) 6.8 Hz), 2.26 (s, 3H), 2.47 (dd, 1H, J ) 7.3, 15.1 Hz), 2.59
(dd, 1H, J ) 7.8, 15.1 Hz), 4.15 (dq, 2H, J ) 3.9, 6.8 Hz), 5.76
(dd, 1H, J ) 7.3, 7.8 Hz), 7.34-7.46 (m, 5H), 7.66-7.69 (m,
1H), 7.82-7.87 (m, 2H); GC/MS m/z 345 (M+). Anal. Calcd
for C18H19NO4S: C, 62.59; H, 5.54; N, 4.06; S, 9.28. Found:
C, 62.72; H, 5.57; N, 3.97; S, 9.13.
Rea ction of Ar om a tic Ca r boxylic Acid s w ith Alk en es.
In a 100-mL two-necked flask was placed MS 4A (400 mg),
which was then dried at 150 °C in vacuo overnight. Then,
Pd(OAc)2 (0.05-0.1 mmol) and Cu(OAc)2‚H2O (0.05-0.1 mmol)
were added. After the apparatus was evacuated by pumping,
nitrogen (750 mL) was introduced. Then, an acid (1 mmol), 2
(3 mmol), DMF (5 mL), and air (150 mL) were injected into
the flask, and the resulting mixture was stirred at 100-120
°C for 6-18 h. After cooling, the reaction mixture was
extracted with diethyl ether and dried over sodium sulfate.
Product was isolated by column chromatography on silica gel
using hexanes-ethyl acetate as eluent.
(Z)-3-Ben zylid en en a p h th o[1,2-c]fu r a n -1(3H)-on e (23):
mp 213.5-214.5 °C; H NMR δ 6.51 (s, 1H), 7.35 (t, 1H, J )
7.3 Hz), 7.44 (t, 2H, J ) 7.3 Hz), 7.63 (dt, 1H, J ) 1.0, 6.8 Hz),
7.73 (dt, 1H, J ) 1.0, 6.8 Hz), 7.76 (d, 1H, J ) 8.8 Hz), 7.91 (d,
2H, J ) 7.3 Hz), 7.95 (d, 1H, J ) 8.3 Hz), 8.13 (d, 1H, J ) 8.8
Hz), 8.90 (d, 1H, J ) 8.3 Hz); HRMS m/z (M+) calcd for
19H12O2 272.0837, found 272.0838. Anal. Calcd for
19H12O2: C, 83.81; H, 4.44. Found: C, 83.63; H, 4.46.
1H-3-P h en yln a p h th o[2,3-c]p yr a n -1-on e (24): mp 180.5-
1
C
C
181 °C; 1H NMR δ 7.07 (s, 1H), 7.41-7.50 (m, 3H), 7.55 (t,
1H, J ) 7.6 Hz), 7.64 (t, 1H, J ) 7.6 Hz), 7.91-7.92 (m, 4H),
8.02 (d, 1H, J ) 8.3 Hz), 8.93 (s, 1H); 13C NMR δ 101.92,
118.97, 124.30, 125.13, 126.67, 127.69, 128.81, 129.43, 129.76,
129.77, 132.00, 132.13, 132.21, 132.39, 136.61, 152.00, 162.62;
HRMS m/z (M+) calcd for C19H12O2: 222.0681, found 222.0662.
Anal. Calcd for C19H12O2: C, 83.81; H, 4.44. Found: C, 83.45;
H, 4.57.
Ack n ow led gm en t. This work was partly supported
by a Grant-in-aid for Scientific Research from the
Ministry of Education, Science, Sports, and Culture,
J apan. We thank Prof. K. Yamamoto of Science Uni-
versity of Tokyo in Yamaguchi for his useful suggestion
and Ms. Y. Miyaji and Ms. T. Muneishi of the Instru-
mental Analysis Center, Osaka University, for helpful
assistance in obtaining NMR spectra.
3-(Bu toxyca r bon yl)m eth ylp h th a lid e (18): oil; 1H NMR
δ 0.94 (t, 3H, J ) 7.3 Hz), 1.37 (tq, 2H, J ) 7.3, 7.3 Hz), 1.62
(m, 2H), 2.88 (dd, 1H, J ) 6.6, 16.6 Hz), 2.95 (dd, 1H, J ) 6.8,
16.6 Hz), 4.17 (t, 2H, J ) 6.8 Hz), 5.89 (t, 1H, J ) 6.8 Hz),
7.51 (d, 1H, J ) 7.8 Hz), 7.56 (t, 1H, J ) 7.3 Hz), 7.69 (dt, 1H,
J ) 1.0, 7.8 Hz), 7.92 (d, 1H, J ) 7.3 Hz); HRMS m/z (M+)
calcd for C14H16O4 248.1048, found 248.1046. Anal. Calcd for
J O980584B
(16) Elix, J . A.; Murphy, D. P. Aust. J . Chem. 1975, 28, 1559.
(17) J ones, P. R.; Weisman, G. R.; Baillargeon, M. J .; Gosink, T. A.
J . Org. Chem. 1980, 45, 3618.
C
14H16O4: C, 67.73; H, 6.50. Found: C, 67.67; H, 6.57.