Synthesis of mono-, di-, and tri- phenyl arenes by sequential photostimulated S(RN)1 and Pd(0)-catalyzed cross coupling reactions on aryl halides

Article abstract of DOI:10.1055/s-2000-6503

The photostimulated reaction of Me₃Sn^- ion with mono-, di-, and trichloro- arenes in liquid ammonia gave very good yields of stannanes by the S(RN)1 mechanism. These products reacted by a palladium-catalyzed cross coupling reaction with halobenzenes to give phenylated products also in very good yields. Similar yields can be obtained in one-pot reactions.

Full text of DOI:10.1055/s-2000-6503

230
LETTER
Synthesis of Mono-, Di-, and Tri- Phenyl Arenes by Sequential
Photostimulated SRN1 and Pd(0)-Catalyzed Cross Coupling Reactions on Aryl
Halides
Eduardo F. Córsico, Roberto A. Rossi*
INFIQC, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria,
5000 Córdoba, Argentina
Fax +54-351-4333030, E-mail: rossi@dqo.fcq.unc.edu.ar
Received 1 December 1999
NH2, NR2, and SO2R. Substituents such as -O- or -NO2 are
Abstract: The photostimulated reaction of Me3Sn- ion with
not suitable, except when arylazo phenyl sulfide are used
mono-, di-, and trichloro- arenes in liquid ammonia gave very good
yields of stannanes by the SRN1 mechanism. These products reacted
by a palladium-catalyzed cross coupling reaction with halobenzenes
as substrates.11 When the substrate has two or three chlo-
rines as leaving groups, it is possible to obtain di and tri
to give phenylated products also in very good yields. Similar yields substitution products in high yields.12
can be obtained in one-pot reactions.
We thought that the photostimulated reaction of mono-,
di- and trichloroarenes with Me3Sn- ions in liquid ammo-
nia to synthesize the trimethylarylstannanes followed by
the Pd(0) cross coupling reaction with haloarenes would
be an important approach for the synthesis of arylated or
polyarylated compounds. Thus, we undertook the study of
the palladium catalyzed reaction of trimethylarylstan-
nanes, synthesized by the SRN1 mechanism, with mono-,
di- and trichloroarenes as a model reaction for this meth-
odology. Also we performed both reactions in one-pot
procedures.
Key words: Stille, SRN1 reactions, cross coupling, photostimulation
For more than a decade, the palladium-catalyzed coupling
of organotin compounds with carbon electrophiles,
known as the Stille reaction,1 has been shown to be a very
important tool in organic synthesis.2
There are several methods of synthesis for trialkylaryl-
stannanes, typically by the reaction of aryl lithium or or-
ganomagnesium derivatives with trialkyltin halides.
These reactions have the drawback that many substituents
on the aromatic ring are incompatible with the formation
of aryl lithium or organomagnesium derivatives.3 Another
approach is the Stille reaction of aryl halides4 or aryl
triflates5 with hexamethyl- and hexabutyldistannanes.
Bis(trimethylstannyl)arenes can also be synthesized using
palladium catalysis. Thus, the reaction of 3,5-dibromobi-
phenyl with hexamethydistannane gave 90% yield of the
ditin product; other examples yielded 40-60% yield of di-
substitution.6
The reaction of p-cyanophenyltrimethylstannane13 with
PhI and Pd(PPh3)2Cl2 (6 mol%) as catalyst in DMF
(80 °C, 3 h), afforded the coupled product 4-biphenycar-
bonitrile in 81% yield.14
When the distannane 1a (0.547 g, 1.35 mmol) was heated
at 80 °C during 24 h in the presence of PhBr (0.424 g, 2.70
mmol) and Pd(PPh3)2Cl2 (3 mol%) in DMF as solvent,
m-terphenyl 2a was obtained (0.302 gr, 97% isolated
yield) (Scheme 1).
There are few examples of the reactions of bis(trimethyl-
stannyl)arenes and heteroarenes with aryl halides which
afford a double arylation by the palladium cross coupling
reaction. Thus, the palladium catalyzed reaction of 3,4-
bis(tributylstannyl)furan with bromo or iodoarenes gave
45-85% of diarylation7 and the reaction of 3-bromopyri-
dine with 2,4-bis(trimethylstannyl)pyridine gave 48%
yield of diheteroarylated product.8 Other examples gave
low yields (6-13% yield) of double arylation.9 As far as
we know there is no report of triphenylation on tris(trim-
ethylstannyl) arenes.2
Scheme 1
Under the same reaction conditions, the distannane 1b
(0.609 g, 1.50 mmol) reacted with PhBr (0.477 g, 3.0
mmol) and Pd(PPh3)2Cl2 (3 mol%) to yield 0.310 g (90%
isolated yield) of p-terphenyl 2b. The reaction of 2,6-
di(trimethylstannyl)pyridine 1c (0.560 gr, 1.38 mmol)
with PhI (0.571 gr, 2.80 mmol) (xylene, 140 °C, 24 h) and
Pd(PPh3)2Cl2 (5 mol%), afforded the diphenylated pyri-
dine 2c (72%), together with 25% yield of 2-phenylpyri-
dine.
We have previously described the photostimulated reac-
tions of trimethylstannyl anions which gave very good to
excellent yields of substitution products with a number of
chloro or dichloro arenes and heteroarenes by the SRN1
mechanism in liquid ammonia.10
Many substituents are compatible with the SRN1 mecha-
-
nism, such as CO2 , CO2R, CONR2, RO-, -CN, R, aryl,
Synlett 2000, No. 2, 230–232 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Synthesis of Mono-, Di-, and Tri- Phenyl Arenes
231
We studied the possibility of performing a triphenylation vious reactions. Product 2b was obtained in 71% yield
reaction. Thus, the reaction of the tristannane 3 (0.283 gr, (Scheme 3). In the same manner, 5c (1.40 mmol) was ir-
0.5 mmol) with PhI (0.306 gr, 1.50 mmol) and radiated (90 min) with Me3Sn- ions (3.20 mmol), and after
Pd(PPh3)2Cl2 (5 mol%) gave the triphenylated product 4 evaporation of the solvent, xylene was added followed by
in 89% yield (Scheme 2).
PhI (0.571 g, 2.80 mmol) and Pd(PPh3)2Cl2 (5 mol%)
(140 °C, 24 h), affording 2c (60%), together with 27% of
2-phenylpyridine.
We studied the one-pot reaction with 1,3,5-trichloroben-
zene as substrate. The photostimulated reaction (105 min)
of 1,3,5-trichlorobenzene (0.091 g, 0.5 mmol) with
Me3SnNa (0.984 g, 5 mmol) in liquid ammonia was fol-
lowed by addition of methyl iodide. After evaporation of
the ammonia, the residue was redissolved in DMF. PhI
(0.306 g, 1.5 mmol) and Pd(PPh3)2Cl2 (5 mol%) were then
added, and the rest of the procedure was similar to the pre-
vious reactions. Product 4 was obtained in 61% isolated
yield together with 27% of 2a. This decrease in the overall
yield for product 4 when comparing the step-wise reaction
(89%) and the one pot-process (61%) can be accounted
for the presence of 1a in the starting mixture is due that the
photostimulated reaction of 1,3,5-trichlorobenzene with
Me3Sn- ions affords 70% of 3 and 20% of 1a.
Scheme 2
We also studied the possibility of performing the synthe-
sis of the distannane and the Stille reaction in a one-pot
procedure. A solution of p-chlorobenzonitrile (0.137 g,
1.00 mmol) in 250 mL of dry liquid ammonia and
Me3SnNa (1.2 mmol) was irradiated (two 250-W UV
lamps) during 1 h. The reaction was quenched by adding
methyl iodide (0.030 g, 0.2 mmol).15 Then the ammonia
was allowed to evaporate, and the residue was redissolved
in DMF. To this solution, PhI (0.242 g, 1.19 mmol) and
Pd(PPh3)2Cl2 (5.5 mol%) were added and heated at 80 °C
for 3 h, and the product 4-biphenycarbonitrile was ob-
tained in 63%.
All these results indicated that the SRN1 mechanism is an
excellent method to obtain stannanes by the photostimu-
lated reactions of mono-, di- and trichloroarenes with
Me3Sn- in liquid ammonia. The stannanes thus obtained
can be arylated by further reaction with bromo- or io-
doarenes through the palladium catalyzed reactions (or to
perform other palladium-catalyzed reactions). Further
work is in progress to examine the reaction conditions and
to extend its scope by using different mono- and dichloro-
arenes and heteroarenes in reactions with Me3Sn- ions fol-
lowed by a palladium-catalyzed reaction with aryl halides
and other catalyzed reactions in a stepwise or one-pot con-
ditions.
A solution of m-dichlorobenzene (5a) (0.441 g, 3.00
mmol) in 250 mL of dry liquid ammonia and Me3SnNa
(1.315 g, 6.6 mmol) was irradiated during 90 min. The
reaction was quenched by adding methyl iodide (0.085 g,
0.60 mmol). Then the ammonia was allowed to evaporate.
The residue was redissolved in DMF. To this solution
PhBr (0.942 g, 6.0 mmol) and Pd(PPh3)2Cl2 (3 mol%)
were added, and reacted as described above. The
product 2a was obtained in 76% yield (duplicated run)
(Scheme 3).
Acknowledgement
This work was supported in part by the Consejo de Investigaciones,
Provincia de Córdoba (CONICOR), the Consejo Nacional de Inve-
stigaciones Científicas y Técnicas (CONICET), SECYT, Universi-
dad Nacional de Córdoba and FONCYT, Argentina. E.F.C
gratefully acknowledges receipt of a fellowship from CONICET.
References and Notes
(1) Milstein, D. Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636.
Stille, J. K. Angew. Chem. Int. Ed. Engl. 1986, 25, 508.
(2) For reviews see Mitchell, T. N. Synthesis 1992, 803; Farina,
V.; Krishnamurthy, V.; Scott, W. J. In The Stille Reaction,
Organic Reactions Vol. 50, Paquette, L. A., Ed.; Wiley:
Chichester, 1997; p.1.
Scheme 3
(3) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry,
Part B; 3rd ed.; Plenum: New York, 1990; p 575, and
references cited therein.
(4) Azizian, H., Heaborn, C.; Pidcock, A. J. Organomet. Chem.
1981, 215, 49.
(5) Farina, V.; Krishnan, T. J. Am. Chem. Soc. 1991, 113, 9585.
(6) Kelly, T. R.; Bridger, G. J.; Zhao, C. J. Am. Chem. Soc. 1990,
112, 8024.
We studied the photostimulated reaction (90 min) of
p-dichlorobenzene (5b) (0.441 g, 3.0 mmol) with
Me3SnNa (1.315 g, 6.6 mmol) in liquid ammonia fol-
lowed by addition of methyl iodide. After evaporation of
the ammonia, the residue was dissolved in DMF. PhBr
(0.942 g, 6.0 mmol) and Pd(PPh3)2Cl2 (3 mol%) were then
added, and the rest of the procedure was similar to the pre-
(7) Yang, Y.; Wong, H. N. C. Tetrahedron 1994, 50, 9583.
Synlett 2000, No. 2, 230–232 ISSN 0936-5214 © Thieme Stuttgart · New York

232
E. F. Córsico, R. A. Rossi
LETTER
(8) Yamamoto, Y.; Azuma, Y.; Mitoh, H. Synthesis 1986, 564.
(9) Gronowitz, S.; Peters, D. Heterocycles 1990, 30, 645. Otsubo,
T.; Kono, Y.; Hozo, N.; Miyamoto, H. Aso, Y.; Ogura, F.;
Tanaka, T.; Sawada, M. Bull. Chem. Soc. Jpn. 1993, 66, 2033.
Lamba, J. J. S.; Tour, J. M. J. Am. Chem. Soc. 1994, 116,
11723.
(14) 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 were
added 20 mL of DMF, and afterwards the stannane 1 (0.425 g,
1.6 mmol), PhI (0.347 g, 1.7 mmol) and the catalyst
Pd(PPh3)2Cl2 (0.056 g, 0.080 mmol, 5%) and the solution was
heated to 80 °C during 3 h. The solution was filtered and water
(50 mL) was added and then extracted three times with diethyl
ether. The product was quantified by GLC using the internal
standard method compared with authentic samples. Products
were isolated by column chromatography and their
(10) Yammal, C. C.; Podestá, J. C.; Rossi, R. A. J. Org. Chem.
1992, 57, 5720.
(11) For reviews, see: (a) Rossi, R. A.; de Rossi, R. H. Aromatic
Substitution by the SRN1 Mechanism; ACS Monograph 178:
Washington, DC, 1983. (b) Norris, R. K. Comprehensive
Organic Synthesis, Ed. Trost B. M. 1991, 4, 451. (c) Rossi, R.
A., Pierini A. B., Peñéñory, A.B. The Chemistry of Functional
Group, Patai S.; Rappoport, Z., Ed.,Wiley: Chichester, 1995;
Supl. D2, Ch 24, 1395. Rossi, R. A.; Pierini, A. B; Santiago,
A. N. In Aromatic Substitution by the SRN1 Reaction, Organic
Reactions Vol. 54, Paquette, L. A.; Bittman, R., Eds.; Wiley:
Chichester, 1999. p. 1.
spectroscopic data agreed with those reported in the literature,
see Properties of Organic Compounds, Version 5.0, CRC
Press Data Base, CRC Press: Boca Raton, 1996.
(15) The excess of Me3SnNa would react with methyl iodide to
form Me4Sn. It is more difficult to transfer a methyl group
than a phenyl ring, see ref. 2. No toluene was found in all these
reactions.
(12) Córsico, E. F.; Rossi, R. A., Synlett 2000, 227.
(13) Prepared by the photostimulated reaction of p-chloro-
benzonitrile and Me3Sn- ion in liquid ammonia in 85% yield,
see ref. 12.
Article Identifier:
1437-2096,E;2000,0,02,0230,0232,ftx,en;S01399ST.pdf
Synlett 2000, No. 2, 230–232 ISSN 0936-5214 © Thieme Stuttgart · New York