Sequential photostimulated reactions of trimethylstannyl anions with aromatic compounds followed by palladium-catalyzed cross-coupling processes

Article abstract of DOI:10.1021/jo016199v

The photostimulated reactions of several mono-, di-, and trichloroarenes and aryltrimethylammonium salts with Me₃Sn^- ions in liquid ammonia gave good yields of stannanes by the S_RN1 mechanism. If the chloroarenes are not soluble in liquid ammonia, diglyme is another solvent to perform these reactions. The stannanes thus obtained can be arylated by further reaction with haloarenes through palladium-catalyzed reactions. If the palladium-catalyzed reaction is performed with a chloroiodoarene as substrate, the stannane reacts faster by the C-I bond via chemoselective cross-coupling reaction to give a chloroarene as product, which can be further arylated by a consecutive S_RN1-Stille reaction or react with other substrates by another palladium-catalyzed reaction. These sequential reactions can also be performed with substrates with two leaving groups to give products in high yields.

Full text of DOI:10.1021/jo016199v

J . Org. Chem. 2002, 67, 3311-3316
3311
Sequ en tia l P h otostim u la ted Rea ction s of Tr im eth ylsta n n yl An ion s
w ith Ar om a tic Com p ou n d s F ollow ed by P a lla d iu m -Ca ta lyzed
Cr oss-Cou p lin g P r ocesses
Eduardo F. Co´rsico and Roberto A. Rossi*
INFIQC, Departamento de Quı´mica Orga´nica, Facultad de Ciencias Qu´ımicas, Universidad Nacional de
Co´rdoba, Ciudad Universitaria, 5000 Co´rdoba, Argentina
rossi@dqo.fcq.unc.edu.ar
Received October 15, 2001
The photostimulated reactions of several mono-, di-, and trichloroarenes and aryltrimethylammo-
nium salts with Me3Sn- ions in liquid ammonia gave good yields of stannanes by the SRN
1
mechanism. If the chloroarenes are not soluble in liquid ammonia, diglyme is another solvent to
perform these reactions. The stannanes thus obtained can be arylated by further reaction with
haloarenes through palladium-catalyzed reactions. If the palladium-catalyzed reaction is performed
with a chloroiodoarene as substrate, the stannane reacts faster by the C-I bond via chemoselective
cross-coupling reaction to give a chloroarene as product, which can be further arylated by a
consecutive SRN1-Stille reaction or react with other substrates by another palladium-catalyzed
reaction. These sequential reactions can also be performed with substrates with two leaving groups
to give products in high yields.
Sch em e 1
In tr od u ction
The radical nucleophilic substitution, or SRN1 reaction,
is a chain process through which an aromatic nucleophilic
substitution is obtained. The scope of the process has
considerably increased, and nowadays, it is an important
synthetic possibility to achieve substitution of different
substrates.1 Several nucleophiles can be used such as
carbanions and anions from compounds bearing hetero-
atoms, which react to form new C-C or C-heteroatom
bond in good yields. Many substituents are compatible
with the SRN1 mechanism such as CO2-, CO2R, CONR2,
RO-, CN, R, aryl, NH2, NR2, and SO2R. Substituents such
as -O- or -NO2 are not suitable except when arylazo
phenyl sulfides are used as substrates.1
that afforded ArSnMe3 in very good to excellent yields
(70-100%).3 The fact that there is no reaction in the dark
but only under irradiation and that the photostimulated
reactions are inhibited by p-dinitrobenzene (p-DNB), a
well-known inhibitor of SRN1 reactions, indicates that
these reactions occur by the SRN1 mechanism. These
reactions are an alternative route to the synthesis of
stannanes, avoiding the use of Grignard reagents or
organolithium compound. These reactions can also be
carried out in DMSO as solvent under irradiation.4
The SRN1 reactions of dihaloarenes with nucleophiles
afford either the monosubstitution or disubstitution
product, depending on the structure of the substrate, the
nature of the nucleofugal group, or the nucleophile.1 We
found that several dichloroarenes and dichloropyridines
give the disubstitution product in high yield and that the
photostimulated reaction of 1,3,5-trichlorobenzene in the
presence of an excess of Me3Sn- ion affords 71% of the
trisubstitution product.5 Mono- and distannanes can also
be formed from diethylaryl phosphonates6 or aryltrimeth-
ylammonium salts7 by the SRN1 mechanism.
This chain process requires an initiation step. In a few
systems, spontaneous electron transfer (ET) from the
nucleophile to the substrate has been observed. When
the ET does not occur spontaneously, it can be induced
by light stimulation.1 The propagation steps of SRN
1
mechanism are presented in Scheme 1. Overall, eqs 1-3
depict a nucleophilic substitution (eq 1,3) in which
radicals and radical anions are intermediates.
The reaction of triorganostannyl ions as nucleophiles
with aryl halides has long been known, and the products
obtained depend on the leaving group, nucleophile,
solvent, and reaction conditions.2 We have described the
photostimulated reactions of trimethylstannyl ions
(Me3Sn-) with several chloroarenes in liquid ammonia
(1) For reviews, see: (a) Rossi, R. A.; de Rossi, R. H. Aromatic
Substitution by the SRN1 Mechanism; ACS Monograph 178; American
Chemical Society: Washington, DC, 1983. (b) Norris, R. K. In
Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon Press:
New York, 1991; Vol. 4, p 451. (c) Rossi, R. A., Pierini A. B., Pen˜e´n˜ory,
A. B. In The Chemistry of Functional Groups, Patai S.; Rappoport, Z.,
Ed., Wiley, Chichester, Supl. D2, 1995, Ch 24, p 1395. (d) Rossi, R. A.;
Pierini, A. B.; Santiago, A. N. Aromatic Substitution by the SRN1
Reaction. In Organic Reactions; Paquette, L. A., Bittman, R., Eds.;
Wiley: New York, 1999; Vol. 54, p 1.
(2) (a) Wursthorn, K. R.; Kuivila, H. G.; Smith, G. F. J . Am. Chem.
Soc. 1978, 100, 2789. (b) Wursthorn, K. R.; Kuivila, H. G. J . Organomet.
Chem. 1976, 105, C6. (c) Quintard, J . P.; Hauvette-Frey, S. J .
Organomet. Chem. 1976, 112, C11. (d) Quintard, J . P.; Hauvette-Frey,
S. J . Organomet. Chem. 1978, 159, 147.
(3) Yammal, C. C.; Podesta´, J . C.; Rossi, R. A. J . Org. Chem. 1992,
57, 5720.
(4) Lockhart, M. T.; Chopa, A. B.; Rossi, R. A. J . Organomet. Chem.
1999, 582, 229.
(5) Co´rsico, E. F.; Rossi, R. A. Synlett 2000, 227.
10.1021/jo016199v CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/25/2002

3312 J . Org. Chem., Vol. 67, No. 10, 2002
Co´rsico and Rossi
For more than a decade, the palladium-catalyzed
coupling of organotin compounds with carbon electro-
philes, known as the Stille reaction,8 has been shown to
be a very important tool in organic synthesis.9 Another
approach to the synthesis of aryltrialkylstannanes is the
palladium-catalyzed cross-coupling reaction of aryl ha-
lides10 or aryl triflates11 with hexamethyl- and hexabu-
tyldistannanes. Bis(trimethylstannyl) arenes can also be
synthesized by the palladium-catalyzed reactions; thus,
the reaction of 3,5-dibromobiphenyl with hexamethyl-
distannane gave 90% yield of the ditin product; other
examples yielded 40-60% disubstitution.12 There are few
examples involving reactions of bis(trimethylstannyl)-
arenes and -heteroarenes with aryl halides, which afford
a double arylation by the palladium cross-coupling reac-
tion. The examples are known afford modest to good
yields (6-85% yield) of double arylation.13
The reactions of the above sequences were investigated
in order to foster a methodology to build large molecules
and to know the scope and the limitations of this
synthetic strategy, with chloro- and dichloroarenes as
substrates.
Resu lts a n d Discu ssion
The stannanes obtained by the SRN1 mechanism re-
acted by a palladium-catalyzed cross-coupling reaction
with halobenzenes to give phenylated products also in
very good yields.14 For instance, m- and p-bis(trimethyl-
stannanyl)benzenes obtained by the SRN1 mechanism
react with iodobenzene in a cross-coupling reaction
catalyzed by palladium to afford m- and p-terphenyls in
high yields. Similarly, 1,3,5-tris(trimethylstannanyl) ben-
zene, upon treatment with iodobenzene and palladium,
furnished 1,3,5-triphenylbenzene in 89% yields.14 This is
the first report of a trisubstitution by a cross-coupling
reaction catalyzed by palladium. Similar yields can be
obtained in one-pot reactions.14
The fact that chloroarenes react with Me3Sn- ions
under irradiation to form aryltrimethylstannanes and
that in the palladium-catalyzed reaction with stannanes
the reactivity of iodoarenes is much greater than that of
chloroarenes, a substrate bearing both leaving groups,
chlorine and iodine, will react faster by the C-I bond
(product Ar-Ar1-Cl, eq 4) in a cross-coupling reaction
with a stannane catalyzed by palladium. This will allow
the remainder leaving group, chlorine, to react later in
another SRN1-type of reaction to form an organostannyl
intermediate (product Ar-Ar1-SnMe3 (eq 5a), which can
ultimately furnish product Ar-Ar1-Ar2 (eq 5a) by a
cross-coupling palladium-catalyzed reaction. Or else, the
product obtained in eq 4 by another palladium-catalyzed
reaction with a substrate Nu may furnish the product of
eq 5b.
The photostimulated reaction of p-chlorobenzonitrile
with Me3Sn- ions in liquid ammonia affords the stannane
1 (94%, 85% isolated yield).5 The reaction of 1 with PhI
and Pd(PPh3)2Cl2 as catalyst in DMF affords the coupling
product biphenyl-4-carbonitrile in 81% yield.14 When a
solution of 1, p-chloroiodobenzene (2), and Pd(PPh3)2Cl2
in DMF was heated to 80 °C for 3 h, the substitution
product 3 (72%) and the dechlorinated product 4 (25%)
were obtained (eq 6). Product 4 is formed by the phenyl-
chlorophenyl ring exchange between the palladium center
and phosphine ligands in the palladium(II) complexes.15
When the catalyst was in only 2 mol % under the same
experimental conditions, the yield of 3 increases up to
was 91%, and no product 4 was found (Table 2, entries 1
and 2).
The photostimulated reaction of 3 and Me3Sn- ions in
liquid ammonia afforded stannane 5 in 94% yield (eq 7)
(Table 1, entry 1). When the stannane 5 thus obtained
was allowed to react with 1-iodonaphthalene (6) and Pd-
(PPh3)2Cl2 in DMF (80 °C, 4 h), product 7 was obtained
in high yields (eq 7) (Table 2, entry 3).
(6) Chopa, A. B.; Lockhart, M. T.; Silbestri, G. Organometallics 2000,
19, 2249.
(7) Chopa, A. B.; Lockhart, M. T.; Silbestri, G. Organometallics 2001,
20, 3358.
(8) (a) Milstein, D.; Stille, J . K. J . Am. Chem. Soc. 1978, 100, 3636.
(b) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
(9) For reviews, see: (a) Mitchell, T. N. In Metal Catalysed Cross-
Coupling Reactions; Diederich F., Stang, P. J ., Eds.; Wiley VCH Verlag
GmbH: Weinheim, 1998; p 167. (b) Farina, V.; Krishnamurthy, V.;
Scott, W. J . The Stille Reaction. In Organic Reactions; Paquette, L.
A., Ed.; Wiley: New York, 1997; Vol. 50, p 1.
(10) Azizian, H.; Heaborn, C.; Pidcock, A. J . Organomet. Chem. 1981,
215, 49.
(11) Echavarren, A. M.; Stille, J . K., J . Am. Chem. Soc. 1987, 109,
5478.
(12) Kelly, T. R.; Bridger, G. J .; Zhao, C. J . Am. Chem. Soc. 1990,
112, 8024.
(13) (a) Gronowitz, S.; Peters, D. Heterocycles 1990, 30, 645. (b)
Otsubo, T.; Kono, Y.; Hozo, N.; Miyamoto, H.; Aso, Y.; Ogura, F.;
Tanaka, T.; Sawada, M. Bull. Chem. Soc. J pn. 1993, 66, 2033. (c)
Lamba, J . J . S.; Tour, J . M. J . Am. Chem. Soc. 1994, 116, 11723. (d)
Yang, Y.; Wong, H. N. C. Tetrahedron 1994, 50, 9583. (e) Yamamoto,
Y.; Azuma, Y.; Mitoh, H. Synthesis 1986, 564.
(15) (a) Kong, K.-C.; Cheng, C.-H. J . Am. Chem. Soc. 1991, 113,
6313. (b) Segelstein, B. E.; Butler, T. W.; Chenard, B. L. J . Org. Chem.
1995, 60, 12.
(14) Co´rsico, E. F.; Rossi, R. A. Synlett 2000, 230.

Sequential SRN1-Pd(0) Reactions
J . Org. Chem., Vol. 67, No. 10, 2002 3313
Ta ble 1. Rea ction s of Ch lor oa r en es a n d Rela ted Su bstr a tes w ith Me3Sn - Ion s
entry
substrate (mmol)
Me3Sn- (mmol)
solventa
conditions (min)
Cl-
%
substitution productb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
3 (0.52)
9 (1.00)
0.62
2.20
4.00
4.00
6.00
6.00
8.80
8.80
6.00
6.00
4.80
4.80
2.20
2.20
2.20
1.00
3.88
NH3
NH3
hν (110)
hν (120)
dark (60)
hν (60)
dark (40)
hν (40)
dark (60)
hν (60)
dark (140)
hν (140)
dark (120)
hν (90)
dark (50)
dark (50)m
hν (50)
hν (90)
hν (180)
98
94
c
17
94
98
94f
p-NCC6H4Cl (1.00)
p-NCC6H4Cl (1.00)
1-ClC10H7 (1.50)
1-ClC10H7 (1.50)
m-Cl2C6H4 (1.10)
m-Cl2C6H4 (1.10)
1,3,5-Cl3C6H3 (0.40)
1,3,5-Cl3C6H3 (0.40)
9 (0.60)
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
diglyme
NH3
70d
88e
85g
95h
28i
11f
11, 4j
11, 79k
40
9 (0.60)
97f
PhNMe3I (1.00)
PhNMe3I (1.00)
PhNMe3I (1.00)
14 (0.40)
l
l
l
l
NH3
NH3
NH3
NH3
98
11, 83n
95
p-NH2C6H4Cl (1.13)
100
a
b
The reactions were performed in diglyme (20 mL) and liquid ammonia (250 mL). Determined by GLC, unless otherwise indicated.
c Detected in a small amount but not quantified. C6H5CN was detected but not quantified. e Naphthalene was obtained in 10% yield.
d
f Considering two chlorines per molecule. Disubstitution product. Considering three chlorines per molecule. Trisubstitution product
g
h
i
j
k
l
m
together with 60% yield of the disubstitution product 8. Product 12 in 3% yield. Product 12 in 11% yield. Not quantified. p-DNB (23
mol %) was added. Product 12 in 4% yield.
n
Ta ble 2. P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g Rea ction of Mon o- a n d Dista n n a n es a n d Dip h en yla m in e w ith
Electr op h iles in DMF a
entry
substrate (mmol)
electrophile (mmol)
Pd(PPh3)2Cl2 (mol %)
time (h) (T (°C))
products (yield, %)b
1
2
3
4
5
6
7
8
9
1 (1.50)
1 (1.50)
5 (0.16)
8 (0.56)
8 (0.56)
8 (0.56)
8 (0.56)
11 (0.10)
18 (1.20)
2 (1.50)
2 (1.50)
6 (0.20)
2 (1.15)
2 (2.27)
2 (2.27)
13 (1.12)
6 (0.50)
9 (0.50)
5.0
2.0
5.0
2.0
1.3
1.0
2.2c
5.0
2.9e
3 (80)
3 (80)
4 (80)
1.5 (80)
1.5 (80)
1.5 (80)
10 (80)
8 (80)
3 (72), 4 (25)
3 (91), 4 (>1)
7 (94)
9 (55), 10 (25)
9 (73), 10 (9)
9 (84), 10 (5)
14 (84)d
17 (81)d
14 (80)
19 (74)d
a
b
In 20 mL of DMF. Determined by GLC, unless otherwise indicated. c The catalyst was Pd2(dba)3, with Ph3As (16.1 mol %) as ligand
and CuI (10.0 mol %) as cocatalyst. The solvent was 90 mL of DMSO. Isolated yield. e The catalysts were Pd2(dba)3, with (o-biphenyl)P(t-
d
Bu)2 (5.3 mol %) as ligand and t-BuOK (1.60 mmol). The solvent was 5 mL of toluene.
The photostimulated reaction of m-dichlorobenzene
and Me3Sn- ions in liquid ammonia afforded the distan-
nane 8 in 90% yield.5 When the distannane 8 was allowed
to react with 2 and the catalyst Pd(PPh3)2Cl2 in DMF,
the disubstitution product 9 and the product with only
one chlorine 10 were obtained in variable yields, depend-
ing on the ratio of 8 and 2 and the amount of the catalysts
(eq 8). When the ratio of 8:2 was 1:4 and 1.0 mol % of
the catalysts, the yield of 9 increased up to 84% and only
5% yield of 9 was obtained (Table 2, entries 4-6).
glyme, and tetraglyme as solvent to yield the substitution
product, but no mechanistic studies have been performed.
There is a report of the reactions of chloro-, bromo-,
dichloro-, and dibromopyridines with Me3Sn- ions in
DME to afford the substitution products (60-88%).16
Musfeldt et al. prepared m- and p-bis(trimethylstannan-
yl)benzene by the reaction of m- and p-diiodobenzene
with NaSnMe3 in diglyme and benzene as solvents (62-
65%).17 Wursthorn and Kuivila reported that the reaction
of o-dibromobenzene with NaSnMe3 in tetraglyme af-
forded the disubstitution product in 42% yield.18 A series
of 1,2-distannylated aromatics and heteroaromatics was
prepared by treating the dibromo precursors with Na-
SnMe3 in tetraglyme.19 No light was used to induce these
reactions.
There is no reaction of p-chlorobenzonitrile or 1-chlo-
ronaphthalene in the dark with Me3Sn- ions in diglyme,
but under irradiation it gives 70% and 88% yields of the
substitution products (Table 1, entries 3-6), lower yields
as in the reaction in liquid ammonia (85% and 90% yields,
respectively). m-Dichlorobenzene did not react in the
dark with Me3Sn- ions in diglyme, but under irradiation
the yield of the disubstitution product was 85% (Table
(16) Yamamoto, Y.; Yanagi, A. Chem. Pharm. Bull. 1982, 30, 1731.
(17) Musfeldt, J . L.; Reynolds, J . R.; Tanner, D. B.; Ruiz, J . P.; Wang,
J .; Pomerantz, M. J . Polym. Sc.: Part B: Polym. Phys. 1994, 32, 2395.
(18) Wursthorn, K. R.; Kuivila, H. G. J . Organomet. Chem. 1977,
140, 29.
(19) Mitchell, T. N.; Bottcher, K.; Bleckmann, P.; Costisella, B.;
Schwittek, C.; Nettelbeck, C. Eur. J . Org. Chem. 1999, 2413.
Compound 9 was completely insoluble in liquid am-
monia and did not react with Me3Sn- ions under irradia-
tion (Table 1, entry 2).
It is known that haloarenes and haloheteroarenes react
with Me3Sn- ions in 1,2-dimethoxyethane (DME), di-

3314 J . Org. Chem., Vol. 67, No. 10, 2002
Co´rsico and Rossi
1, entries 7 and 8), a slightly lower yield compared with
the reaction in liquid ammonia (90% yield). The reaction
of 1,3,5-trichlorobenzene with Me3Sn- ions in liquid
ammonia afforded 71% of the trisubstitution product;
however, only 28% yield was obtained in the photoiniti-
ated reaction in diglyme, together with 60% yield of the
disubstitution product 8 (Table 1, entries 9 and 10). All
these results indicate that in diglyme as solvent, the
yields are lower compared with liquid ammonia. With one
or two leaving groups, the yields are slightly lower, and
with three leaving groups the yields are low compared
with the reactions in liquid ammonia. These results show
that the reduction process is more important in diglyme
than in liquid ammonia.
There is a slow dark reaction of 9 with Me3Sn- ions in
diglyme, but under irradiation the disubstitution product
11 is obtained in 79% yield, and the monosubstitution
product 12 in 11% yield (eq 9) (Table 1, entries 11 and
12). This result indicates that diglyme is a suitable
solvent for the photoinduced SRN1 reactions with Me3Sn-
ions.
disubstitution product 14 is obtained in 84% yield (Table
2, entry 7) (eq 10).
Compound 14 was soluble in liquid ammonia, and in
the photostimulated reaction with Me3Sn- ions, com-
pounds 11 and 12 were obtained in 83% and 4% yields,
respectively (eq 11) (Table 1, entry 16).
As the trimethylammonium is a good leaving group in
SRN1 reactions, it was of interest to know if a chloroarene
with an amino group reacts with Me3Sn- ions by this
mechanism. The amino group as substituent in the
aromatic moiety did not interfere in the reaction with
some nucleophiles, but inhibited or gave low yields with
others.1 For instance, p-bromo-N,N-diethylamine did not
react with pinacolone enolate anions under irradiation
in liquid ammonia,23 but good yields of products are
obtained in the reaction of o-haloanilines and derivatives
with carbanions to obtain indoles.24 o-Iodoaniline gives
only 10% of substitution with benzenethiolate ions.25 The
photostimulated reaction of p-chloroaniline with Me3Sn-
ions in liquid ammonia afforded high yields (95%) of the
substitution product 16 (eq 12) (Table 1, entry 17).
We studied the synthesis of 11 by another route,
changing the leaving group chlorine by trimethylammo-
nium iodide. These salts are quite soluble in liquid
ammonia. It is known that trimethylammonium can act
as a leaving group in SRN1 reactions.20 It can be seen in
Table 1 (entries 13-15) that there is a slow reaction of
phenyltrimethylammonium iodide with Me3Sn- ions in
the dark, reaction that is completely inhibited by p-DNB.
Under irradiation, the substitution product trimeth-
ylphenylstannane is obtained in 98% yield. These results
indicate that trimethylammonium salts are very good
substrates in SRN1 reactions with Me3Sn- ions.
The palladium-catalyzed reaction of stannanes with
haloarenes substituted with the amino group gave low
yields or no reaction. It is known that the amino group
slows down the oxidative addition of palladium(0).9 For
instance, p-iodoaniline gave 57% in a cross-coupling
reaction with a stannane,21 but p-iodo-N,N-dimethylani-
line failed to react.22
When the distannane 11 was allowed to react with 6
in a cross-coupling reaction catalyzed by palladium, the
hydrocarbon 17 was obtained (81%) (Table 2, entry 8) (eq
13).
Stannane 8 with p-iodoaniline did not give the expected
substitution product in a palladium-catalyzed cross-
coupling reaction. As far as we know, there is no example
of a trialkylammonium salt as substituent in the halo-
arene in cross-coupling reactions catalyzed by palladium.
We thought that this group may facilitate the oxidative
addition. In the palladium-catalyzed reaction of stannane
8 with p-iodophenyltrimethylammonium iodide (13), the
(23) Bunnett, J . F.; Sundberg, J . E. Chem. Pharm. Bull. 1975, 23,
2620.
(24) (a) Beugelmans, R.; Roussi, G. Tetrahedron 1981, 37, 393. (b)
Beugelmans, R.; Chbani, M. Bull. Soc. Chim. Fr. 1995, 132, 306. (c)
Galli, C.; Bunnett, J . F. J . Org. Chem. 1984, 49, 3041. (d) Beugelmans,
R.; Chbani, M. Bull. Soc. Chim. Fr. 1995, 132, 729. (e) Estel, L.;
Marsais, F.; Queguiner, G. J . Org. Chem. 1988, 53, 2740. (f) Baum-
gartner, M. T.; Nazareno, M. A.; Murgu´ıa, M. C.; Pierini, A. B.; Rossi,
R. A. Synthesis-Stuttgart 1999, 2053.
(20) (a) Rossi, R. A.; Bunnett, J . F. J . Am. Chem. Soc. 1972, 94, 683.
(b) Bunnett, J . F.; Gloor, B. F. J . Org. Chem. 1973, 38, 4156. (c)
Bunnett, J . F.; Creary, X. J . Org. Chem. 1974, 39, 3611. (d) Bunnett,
J . F.; Gloor, B. F. J . Org. Chem. 1974, 39, 382.
(21) Liebeskind, L. S.; Riesinger, S. W. J . Org. Chem. 1993, 58, 408.
(22) Sakamoto, T.; Yasuhara, A.; Kondo, Y.; Yamanaka, H. Synlett.
1992, 502.
(25) Beugelmans, R.; Chbani, M. Bull. Soc. Chim. Fr. 1995, 132,
290.

Sequential SRN1-Pd(0) Reactions
J . Org. Chem., Vol. 67, No. 10, 2002 3315
P h otostim u la ted Rea ction of Me3Sn - Ion s in Diglym e.
The photostimulated reaction of 1-chloronaphthalene with
Me3Sn- ions is representative of all the reactions. The Me3Sn-
ions (6.00 mmol) were prepared in liquid ammonia with the
procedure described before, and the ammonia was allowed to
evaporate. To the residue was added 20 mL of diglyme, and
1-chloronaphthalene (1.50 mmol) was added and irradiated for
40 min at ca. 0 °C. The reaction was quenched by addiition of
an aqueous solution of NH4NO3 in excess and extracted with
diethyl ether. The chloride ions in the aqueous solution were
determined potentiometrically. The ether extract was washed
twice with water and dried, and the product was quantified
by GLC with the internal standard method compared with an
authentical sample.3
It is known that aryl chlorides can react with amines
with different palladium catalysts and ligands,26 such as
Pd2(dba)3 and (o-biphenyl)-P(t-Bu)2 as ligand.27 When 9
is treated with this catalyst system and diphenylamine
18 as substrate, product 19 was obtained in 74% yield
(Table 2, entry 9) (eq 14).
Con clu sion s
Cr oss-Cou p lin g Rea ction of 1 w ith 2 Ca ta lyzed by P d -
(P P h 3)2Cl2. The following procedure is representative of all
the reactions. Into a three-necked, 50-mL, round-bottomed
flask equipped with a condenser, a nitrogen inlet, and a
magnetic stirrer was added 20 mL of DMF and then the
stannane 1 (1.50 mmol), 2 (1.50 mmol), and the catalyst (0.03
mmol, 2 mol %), and the solution was heated to 80 °C for 3 h.
The solution was filtered, water (50 mL) was added, and then
the solution was extracted three times with diethyl ether. The
product was quantified by GLC using the internal standard
method compared with authentic samples. Products were 3
and 4 isolated by column chromatography on silica gel (elu-
ent: petroleum ether/diethyl ether 75:25), and their spectro-
scopic data agreed with those reported in the literature.
Compound 4 was compared with an authentical sample.14
Compound 3: MS (m/z, rel int) 215 (34, M+ + 2), 213 (100,
M+), 178 (13), 177 (20), 151 (25), 75 (23); white solid; mp 124-
126 °C (lit.30 mp 123-125 °C).
These findings confirm the conclusions that the SRN
1
mechanism is an excellent method to obtain stannanes
by the photostimulated reactions of mono-, di-, and
trichloroarenes with Me3Sn- ions, in liquid ammonia, or
if the chloroarenes are not soluble, diglyme is another
solvent to perform these reactions. The stannanes thus
obtained can be arylated by further reaction with bromo
or iodoarenes through palladium-catalyzed reactions.
Another conclusion that emerges from these results is
that the product obtained with a chloroiodoarene is
another aryl chloride that can be further transformed into
a stannane to give ultimately, by a Pd-catalyzed reaction,
the final product of this sequence. Thus, this sequence
can be successfully applied to build large molecules.
Isola tion a n d Id en tifica tion of th e P r od u cts. 4′-Tr i-
m eth ylsta n n a n ylbip h en yl-4-ca r bon itr ile (5). Compound
5 was purified by column chromatography on silica gel
(eluent: petroleum ether/diethyl ether 70:30): white solid; mp
94-96 °C; 1H NMR (200.13 MHz; CDCl3/Me4Si) δ 0.34 (s, 9
Exp er im en ta l Section
Ma ter ia ls. p-Chlorobenzonitrile, p-chloroiodobenzene, m-
dichlorobenzene, p-iodoaniline, 1-iodonaphthalene, diphenyl-
amine, and trimethylstannyl chloride were commercially
available and used as received. p-Iodophenyltrimethylammo-
nium iodide (90%) was obtained from the reaction of p-
iodoaniline and methyl iodide in excess in DMF and 2-meth-
ylpyridine by the standard procedure described in the litera-
ture:28 white solid, mp 193-195 °C dec (lit.29 mp 196-198 °C
dec). Diglyme was treated with pellets of NaOH (1 day), was
refluxed with sodium metal (4-5 h), was vacuum distilled
under nitrogen atmosphere, and finally stored with sodium
wires under nitrogen in the dark.
2
H, J (117-119SnCH) ) 53.0, 55,2 Hz), 7.51-7.79 (m, 8 H); 13C
NMR (50.288 MHz; CDCl3) δ (J (119Sn-13C)) -2.48, 110.90,
118.93, 126.67 (44.72 Hz, C2′), 127.69, 132.60, 136.56 (36.59
Hz, C3′), 138.99, 143.41, 145.75; MS (EI, m/z, rel int) 343 (2,
M+), 328 (100, M+ - CH3), 298 (34), 179 (7), 152 (11). Anal.
Calcd. for C16H17NSn: C, 56.19; H, 5.01; N, 4.10; Sn, 34.70.
Found: C, 56.68; H, 5.42; N, 4.07.
4′-Na p h t h a len -1-ylb ip h en yl-4-ca r b on it r ile (7). Com-
pound 7 was purified by column chromatography on silica gel
(eluent: petroleum ether/diethyl ether 95:5): white solid; mp
159-161 °C; 1H NMR (200.13 MHz; CDCl3; Me4Si) δ 7.38-
7.57 (m, 8 H), 7.69-7.94 (m, 7 H); 13C NMR (50.288 MHz;
CDCl3) δ 111.34, 119.24, 125.75, 126.06, 126.22, 126.54, 127.27,
127.43, 128.00, 128.35, 128.73, 131.15, 131.80, 132.98, 134.17,
138.32, 139.64, 141.64, 145.62; MS (EI, m/z, rel int) 305 (100,
M+), 304 (41), 278 (2), 203 (15), 202 (17), 178 (1). 152 (33), 102
(3); HRMS (EI) calcd for C23H15N 305.12045, found 305.12048.
P h otostim u la ted Rea ction of Me3Sn - ion s in Liqu id
Am m on ia . Irradiation was conducted in a reactor equipped
with two 250-W UV lamps emitting maximally at 350 nm
(water-refrigerated). The following procedure of the reaction
of 4′-chlorobiphenyl-4-carbonitrile (3) with Me3Sn- ions is
representative of all the reactions. Into a three-necked, 500-
mL, round-bottomed flask equipped with a coldfinger con-
denser charged with dry ice-ethanol, a nitrogen inlet, and a
magnetic stirrer was condensed 250 mL of ammonia previously
dried with sodium metal under nitrogen. The Me3SnCl (0.62
mmol) and sodium metal (1.30 mmol) were added. To this
solution was added 0.52 mmol of 3, and the mixture was
irradiated for 110 min. The reaction was quenched by addition
of NH4NO3 in excess, and the ammonia was allowed to
evaporate. The residue was dissolved with water and then
extracted with diethyl ether. The chloride ions in the aqueous
solution were determined potentiometrically. The product was
quantified by GLC using the internal standard method.
4,4′′-Dich lor o-[1,1′;3′,1′′]ter p h en yl (9). Compound 9 was
purified by column chromatography on silica gel (eluent:
petroleum ether): white solid; mp 114-116 °C; 1H NMR
(200.13 MHz; CDCl3; Me4Si) δ 7.38-7.68 (m, 11 H), 7.72 (s, 1
H); 13C NMR (50.288 MHz; CDCl3) δ 125.75, 126.26, 128.47,
129.01, 129.44, 133.70, 139.44, 140.74; MS (EI, m/z, rel int)
301 (11, M+ + 2), 300 (63, M+ + 1), 299 (17), 298 (100), 264
(3), 262 (7), 228 (27), 226 (25), 150 (12). Anal. Calcd for C18H12
Cl2: C, 72.26; H, 4.04; Cl, 23.70. Found: C, 72.20; H, 4.29.
-
4,4′′-Bis(tr im eth ylsta n n a n yl)[1,1′;3′,1′′]ter p h en yl (11).
Compound 11 was purified by column chromatography on
silica gel (eluent: petroleum ether): white solid; mp 82-84
(26) (a) Beller, M.; Riermeier, T. H.; Reisinger, C. P.; Herrmann,
W. A. Tetrahedron Lett. 1997, 38, 2073. (b) Sturmer, R. Angew. Chem.,
Int. Ed. Engl. 1999, 38, 3307. (c) Beletskaya, I. P.; Averin, A. D.;
Bessmertnykh, A. G.; Guilard, R. Tetrahedron. Lett. 2001, 42, 4983.
(d) Beletskaya, I. P.; Averin, A. D.; Bessmertnykh, A. G.; Guilard, R.
Tetrahedron Lett. 2001, 42, 4987.
(27) Wolfe, J . P.; Tomori, H.; Sadighi, J . P.; Yin, J . J .; Buchwald, S.
L. J . Org. Chem. 2000, 65, 1158.
(28) Sommer, H. Z.; J ackson, L. L. J . Org. Chem. 1970, 35, 1558.
(29) Bunnett, J . F.; Scamehorn, R. G.; Traber, R. P. J . Org. Chem.
1976, 41, 3677.
1
2
°C; H NMR (200.13 MHz; CDCl3; Me4Si) δ 0.33 (s, 18 H, J
119SnCH) ) 54.6 Hz), 7.35-7.78 (m, 11 H), 7.82 (s, 1 H); 13C
NMR (50.288 MHz; CDCl3) δ -2.12, 126.46, 127.19 (46.08 Hz,
(
C
2,2′′), 129.13, 129.51, 136.65 (36.59 Hz, C3,3′′), 141.45, 141.66,
142.17; MS (EI, m/z, rel int) 496 (3, M+ - 4 CH3), 481 (33),
(30) Giroux, A.; Han, Y.; Prasit, P. Tetrahedron Lett. 1997, 38, 3841.

3316 J . Org. Chem., Vol. 67, No. 10, 2002
Co´rsico and Rossi
466 (20), 348 (31), 263 (100), 247 (85), 232 (72), 228 (40), 152
(9); HRMS (EI) calcd for C23H27 118Sn120Sn ([M - CH3]+)
540.9678, found 540.9679.
Cr oss-Cou p lin g Rea ction of 9 w ith 18 Ca ta lyzed by
P d 2(d ba )3. Into a three-necked, 25 mL, round-bottomed flask
equipped with a condenser, a nitrogen inlet, and a magnetic
stirrer were added 5 mL of toluene followed by substrate 9
(0.50 mmol), HNPh2 (18) (1.20 mmol), the catalyst system Pd2-
(dba)3 (0.029 mmol, 2.9 mol %), o-biphenyl-P(t-Bu)2 (0.053
mmol, 5.3 mol %), and the base t-BuOK (1.60 mmol). The
solution was heated to 80 °C for 14 h. After that, the solution
was filtered, water (40 mL) was added, and then the solution
was extracted three times with diethyl ether. The product 19
was purified by column chromatography on silica gel (eluent:
petroleum ether/diethyl ether 50:50). It was rendered in 74%
yield. N4,N4,N4′′,N4′′-Tetr a p h en yl[1,1′;3′,1′′]ter p h en yl-4,4′′-
d ia m in e (19): white solid; mp 131-133 °C; 1H NMR (200.13
MHz; CDCl3; Me4Si) δ 6.82-7.09 (m, 12 H), 7.20-7.31 (m, 12
H), 7,35-7.59 (m, 7 H), 7.71 (s, 1H); 13C NMR (50.288 MHz;
CDCl3) δ 117.85, 121.01, 122.95, 123.92, 124.46, 125.21, 127.88,
129.28, 135.19, 141.20, 147.32, 147.72; MS (EI, m/z, rel int)
566 (71, M+ + 2), 565 (100, M+ + 1), 564 (49), 397 (1), 283 (4),
244 (2), 168 (5); HRMS (EI) calcd for C42H32N2 564.2565, found
564.2568. Anal. Calcd for C42H32N2: C, 89.33; H, 5.71; N, 4.96.
Found: C, 88.92; H, 5.09.
4-(Tr im eth ylsta n n a n yl)p h en yla m in e (16). Compound
16 was vacuum distilled using a Kugelrohr apparatus, and
the spectroscopic data agreed with those reported in the
literature:18 1H NMR (200.13 MHz; CDCl3; Me4Si) δ 0.19 (s, 9
H, 2J
AA′BB′system, 4 H).
(
119SnCH) ) 53.0 Hz), 3.53 (s, 2 H), 641-7.05 (m,
4,4′′-Din a p h th a len -1-yl[1,1′;3′,1′′]ter p h en yl (17). Com-
pound 17 was purified by column chromatography on silica
gel (eluent: petroleum ether): white solid; mp 163-165 °C;
1H NMR (200.13 MHz; CDCl3; Me4Si) δ 7.16-7.48 (m, 15 H),
7.63-7.98 (m, 11 H); MS (EI, m/z, rel int) 483 (46, M+ + 1),
482 (73, M+), 356 (1), 352 (2), 241 (100), 226 (5), 203 (31), 202
(33), 152 (2). Anal. Calcd for C38H26
Found: C, 94.25; H, 5.74.
: C, 94.57; H, 5.43.
Cr oss-Cou p lin g Rea ction of 8 w ith 13 Ca ta lyzed by
P d 2(d ba )3. Into a three-necked, 250 mL, round-bottomed flask
equipped with a condenser, a nitrogen inlet, and a magnetic
stirrer were added 90 mL of DMSO followed by stannane 8
(0.56 mmol), p-iodophenyltrimethylammonium iodide (13)
(1.12 mmol), the catalyst system Pd2(dba)3 (0.025 mmol, 2.2
mol %), Ph3As (0.180 mmol 16.1 mol %), and CuI (0.112 mmol,
10.0 mol %). This solution was heated to 80 °C for 10 h. The
solution was filtered, and DMSO was distilled. The residue
was recrystallized from methanol to give 14 in 84% yield. 4,4′′-
Bis(tr im eth yla m m on iu m )[1,1′;3′,1′′]ter p h en ylben zen e d i-
iod id e (14): whitish solid; mp 116-118 °C dec; 1H NMR
(200.13 MHz; DMSO-d6; Me4Si) δ 3.71 (s, 18 H), 6.22 (d, 4 H,
J ) 7.7 Hz), 6.95 (d, 4 H, J ) 7.3 Hz), 7.28-7.65 (m, 3 H),
8.29 (s, 1 H); MS (EI, m/z, rel int) 316 (100, M+ - 2 CH3I), 301
(11), 285 (5), 270 (2), 253 (11), 228 (8); HRMS (EI) calcd for
Ack n ow led gm en t. This work was supported in part
by the Consejo de Investigaciones de la Provincia de
Co´rdoba (CONICOR), the Consejo Nacional de Investi-
gaciones Cient´ıficas y Te´cnicas (CONICET), SECYT,
Universidad Nacional de Co´rdoba, and FONCYT, Ar-
gentina. E.F.C. gratefully acknowledges receipt of a
fellowship from CONICET.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR of com-
pounds 5, 7, 9, 11, and 19. This material is available free of
charge via the Internet at http://pubs.acs.org.
C
22H24N2 ([M - 2 CH3I]+) 316.0369, found 316.0380. Anal.
Calcd for C24H30I2N2: I, 42.28. Found: I, 41.7 (determined
potentiometrically).
J O016199V