Palladium-catalyzed cross-coupling reactions of triorganoindium compounds with vinyl and aryl triflates or iodides

Article abstract of DOI:10.1021/ol990939t

(matrix presented) A novel palladium-catalyzed cross-coupling reaction of organoindium compounds with vinyl and aryl triflates or iodides is described. The reaction proceeds for alkyl-, vinyl-, alkynyl-, and arylindium compounds in excellent yields and high chemoselectivity without any excess of the organometallic. Remarkably, indium organometallics transfer efficiently the three organic groups attached to the metal.

Full text of DOI:10.1021/ol990939t

ORGANIC
LETTERS
1999
Vol. 1, No. 8
1267-1269
Palladium-Catalyzed Cross-Coupling
Reactions of Triorganoindium
Compounds with Vinyl and Aryl Triflates
or Iodides
Ignacio Pe´rez, Jose´ Pe´rez Sestelo, and Luis A. Sarandeses*
Departamento de Qu´ımica Fundamental e Industrial, UniVersidade da Corun˜a,
E-15071 A Corun˜a, Spain
qfsarand@udc.es
Received August 12, 1999
ABSTRACT
A novel palladium-catalyzed cross-coupling reaction of organoindium compounds with vinyl and aryl triflates or iodides is described. The
reaction proceeds for alkyl-, vinyl-, alkynyl-, and arylindium compounds in excellent yields and high chemoselectivity without any excess of
the organometallic. Remarkably, indium organometallics transfer efficiently the three organic groups attached to the metal.
The chemistry of indium has recently gained great interest
in organic synthesis because of the chemical properties of
this metal with regard to its reactivity, selectivity, and low
toxicity.1 However, the synthetic applications of indium have
been limited to the use of the metal for allylation and related
reactions in aqueous media2 or organic solvents3 under
Barbier conditions. The use of classic organometallic species
of indium is practically unknown and limited to additions
to chloroalkenes4 and to our recently reported nickel-
catalyzed 1,4-conjugate addition to electron deficient olefins.5
Our belief that indium can achieve the importance of other
main group metals such as boron or tin led us to further
investigate the participation of indium organometallics in
metal-catalyzed reactions. In this Letter, we report the
palladium-catalyzed cross-coupling reaction of triorgano-
indium compounds with vinyl and aryl triflates or iodides
(Scheme 1).
(1) (a) Cintas, P. Synlett 1995, 1087. (b) Marshall, J. A. Chemtracts:
Org. Chem. 1997, 10, 481.
Scheme 1
(2) (a) Allylation of carbonyls: Chan, T. H.; Yang, Y. J. Am. Chem.
Soc. 1999, 121, 3228. (b) Allenylations of carbonyls: Yi, X.-H.; Meng,
Y.; Hua, X.-G.; Li, C.-J. J. Org. Chem. 1998, 63, 7472. (c) Reductive
dimerization of aldimines: Kalyanam, N.; Rao, G. V. Tetrahedron Lett.
1993, 34, 1647.
(3) (a) Allylation of carbonyls: Lloyd-Jones, G. C.; Russell, T. Synlett
1998, 903. (b) Allylation of imines: Choudhury, P. K.; Foubelo, F.; Yus,
M. J. Org. Chem. 1999, 64, 3376. (c) Allylation of enamines: Bossard, F.;
Dambrin, V.; Lintanf, V.; Beuchet, P.; Mosset, P. Tetrahedron Lett. 1995,
36, 6055. (d) Allylation of triple bonds: Fujiwara, N.; Yamamoto, Y. J.
Org. Chem. 1997, 62, 2318. (e) Reformatsky-type reactions: Schick, H.;
Ludwig, R.; Schwarz, K.-H.; Kleiner, K.; Kunath, A. Angew. Chem., Int.
Ed. Engl. 1993, 32, 1191. (f) Allylation of cyclopropenes: Araki, S.;
Nakano, H.; Subburaj, K.; Hirashita, T.; Shibutani, K.; Yamamura, H.;
Kawaki, M.; Butsugan, Y. Tetrahedron Lett. 1998, 39, 6327.
(4) Nomura, R.; Miyazaki, S.-I.; Matsuda, H. J. Am. Chem. Soc. 1992,
114, 2378.
The metal-catalyzed cross-coupling reaction of aryl and
vinyl halides (or pseudohalides) with organometallics is one
of the most straightforward methods currently available for
carbon-carbon bond formation.6 Hitherto, a variety of metals
(Zn, Mg, B, Al, Sn, Cu, Zr) have been used in palladium or
(5) Pe´rez, I.; Pe´rez Sestelo, J.; Maestro, M. A.; Mourin˜o, A.; Sarandeses,
L. A. J. Org. Chem. 1998, 63, 10074.
10.1021/ol990939t CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/25/1999

nickel cross-coupling reactions, with the Sn-organometallics
(Stille reaction),7 organoboron compounds (Suzuki reaction),8
and Zn-organometallics9 being the most common and useful
in organic synthesis. Ideally, this reaction must show high
conversion of the organometallic, high chemoselectivity,
minimization of the side products, and the capacity to form
C-C bonds between the different carbon types (sp3, sp2, and
sp). In this sense, the main synthetic limitations have been
found in the preparation of the organometallics, in the use
of alkyl (sp3) derivatives as coupling partners, and with the
associated toxicity (especially of tin compounds) or side
reactions observed. Additionally, the transfer of only one of
the substituents attached to the metal has been an important
handicap for copper, zinc, and aluminum compounds. The
development of mixed organometallics has overcome this
difficulty in the case of tin and boron.7,8
of triorganoindium compounds to chloroalkenes.4 When the
cross-coupling reaction of 2 was carried out with just 34
mol % of triphenylindium and 3 mol % of Pd(Ph3P)2Cl2,
the coupled product 3a was obtained in 96% yield (Table 1,
Table 1. Results of the Palladium-Catalyzed Cross-Coupling
Reaction of Triorganoindium Compounds 1a-g with
Electrophiles 2, 4, and 6a
entry no.
R
electrophile t (h) product yield (%)b
1
2
3
4
5
6
7
8
9c
10c
11c
12
13
14
15
16
17
18
19
20
21
Ph (1a )
2
4
6
1
3a
3b
3c
3d
3e
3f
3g
5a
5b
5c
5d
5e
5f
5g
7a
7b
7c
7d
7e
7f
96
89
90
93
82
85
92
95
89
94
93
91
91
89
93
97
95
93
90
92
90
CH2dCH (1b)
PhCtC (1c)
TMSCtC (1d )
n-Bu (1e)
Me (1f)
c-C3H5 (1g)
Ph (1a )
CH2dCH (1b)
PhCtC (1c)
TMSCtC (1d )
n-Bu (1e)
Me (1f)
c-C3H5 (1g)
Ph (1a )
CH2dCH (1b)
PhCtC (1c)
TMSCtC (1d )
n-Bu (1e)
Me (1f)
c-C3H5 (1g)
0.5
0.5
1
4
1
3
6
3
1
The cross-coupling reaction of indium organometallics was
envisaged from easily available triorganoindium compounds
(1a-g, Table 1)10 and standard electrophiles as the aryl halide
4-iodotoluene (2) under palladium catalysis (Scheme 2).
1
1.5
4.5
3
Scheme 2
1
0.5
0.5
0.5
1
7
4
7g
The reaction of 4-iodotoluene with triphenylindium (100
mol %) in the presence of a catalytic amount of Pd(Ph3P)2-
Cl2 (3 mol %) afforded, after just half-hour of refluxing, the
cross-coupling product 4-phenyltoluene (3a) in quantitative
yield. Exploring this new reaction, we observed that other
organoindium compounds showed the same quantitative
yields, even when other palladium complexes were used. This
total conversion led us to think that more of one group could
be transferred to the electrophile, a fact that was previously
observed with arylic boron derivatives11 and for the addition
a Reactions were conducted in THF at reflux using 34 mol % of R3In
and 3 mol % of Pd(Ph3P)2Cl2, except for entries 9-11. b Isolated yield based
on the electrophile added. c Pd(dppf)Cl2 (3 mol %) as catalyst.
entry 1), showing that the three phenyl groups attached to
indium are transferred to 2. The reaction with other palladium
complexes such as Pd(PPh3)4 or Pd(CH3CN)2Cl2 led to lower
yields, and in the absence of a palladium catalyst the coupling
product was not observed.
The reaction of alkyl-, vinyl-, and alkynylindium com-
pounds (1b-g) with 2, under the same reaction conditions
(3:1 ratio of electrophile/R3In), afforded the cross-coupling
products 3b-g in good yields (82-93%) and short reaction
times (0.5-4 h, Table 1, entries 2-7).12 Therefore, indium
organometallics proved to be efficient at transferring different
organic groups (sp3, sp2, and sp), with a remarkable aspect
being the coupling of alkylindium derivatives without
observation of â-elimination products.6,13
These results show that indium organometallics transfer
all of the groups attached to the metal in the palladium-
catalyzed cross-coupling reaction.
Expanding this reaction with other types of electrophiles,
we studied the palladium-catalyzed cross-coupling reaction
(6) (a) Tsuji, J. Palladium Reagents and Catalysts; Wiley: Chichester,
U.K., 1995; Chapter 4. (b) Geissler, H. In Transition Metals for Organic
Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998;
Chapter 2.10.
(7) (a) Stille, J. K. Pure Appl. Chem. 1985, 57, 1771. (b) Stille, J. K.
Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (c) Mitchell, T. N. Synthesis
1992, 803. (d) Farina, V.; Krishnamurty, V.; Scott, W. J. Org. React. 1997,
50, 1. (e) Mitchell, T. N. In Metal-catalyzed Cross-coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter
4.
(8) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (b) Suzuki,
A. In Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter 2.
(9) Negishi, E. In Organozinc Reagents; Knochel, P., Jones, P., Eds.;
Oxford University Press: Oxford, U.K., 1999; Chapter 11.
(10) Prepared from organolithium or Grignard reagents by addition to a
THF solution of InCl3. See Supporting Information or ref 5.
(11) (a) Bumagin, N. A.; Bykov, V. V. Tetrahedron 1997, 53, 14437.
(b) Bumagin, N. A.; Tsarev, D. A. Tetrahedron Lett. 1998, 39, 8155.
(12) Representative General Experimental Procedure: A solution of
freshly prepared R3In (0.34 mmol, ca. 0.1 M in dry THF) was added over
a refluxing mixture of the olefinic electrophile (1 mmol) and Pd(Ph3P)2Cl2
(0.03 mmol) in dry THF (4 mL). The resulting mixture was refluxed under
an argon atmosphere until consumption of the starting material (0.5-7 h);
then the reaction was quenched by addition of a few drops of MeOH. Usual
workup and flash chromatography affords the cross-coupling product.
(13) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158.
(14) Ritter, K. Synthesis 1993, 735.
(15) Other palladium catalysts such as Pd(Ph3P)4, Pd(CH3CN)2Cl2, and
Pd(dppe)Cl2 gave lower yields.
1268
Org. Lett., Vol. 1, No. 8, 1999

of organoindium compounds with aryl and vinyl triflates.14
Thus, the reaction of the aryl triflate 4 (Scheme 3) with 34
than for the aryl triflate 4. The coupling products were
obtained, under the same conditions, in shorter reaction times
(0.5-7 h) and with almost quantitative yields (90-97%,
Table 1, entries 15-21).
Scheme 3
The different behavior observed for indium organometal-
lics in the palladium cross-coupling reaction with regard to
the other metals used suggests that the reaction mechanism
pathways could be other than that proposed for the Stille
reaction.16 Nomura and co-workers invoked the large dif-
ference of the bond strength between organoindium com-
pounds and indium halides to explain related results in
coupling with chloroalkenes.17 On the other hand, the
formation of a transient Pd-In complex as intermediate could
be an alternative way to explain our results.18
In conclusion, we describe a novel palladium-catalyzed
cross-coupling reaction of indium organometallics with aryl
halides and aryl and vinyl triflates. In this reaction we show
that, unlike with other metals used in this reaction type, all
the groups attached to the metal are efficiently transferred
(high conversion). Triorganoindium compounds can transfer
different groups in excellent yields and high chemoselec-
tivity. These features make triorganoindium compounds
useful alternatives to other organometallics used in organic
synthesis.
mol % of triphenylindium or the alkylindium derivatives 1e,
1f, and 1g also gave the cross-coupling products in a
chemoselective manner and in excellent yield (91-95%,
Table 1, entries 8, 12, 13, and 14). The reaction with the
alkenyl- and alkynylindium compounds 1b, 1c, and 1d
afforded lower yields of coupling products (25-40%), with
the remainder being recovered as unreacted triflate. In these
cases, the use of Pd(dppf)Cl2 improved the yields signifi-
cantly (89-94%, Table 1, entries 9, 10, and 11).15
When the reaction was tested with the vinyl triflate 6
Further applications of indium organometallics in synthesis
and studies about the mechanism of this reaction are in
progress.
(Scheme 3), we observed, as expected, a higher reactivity
(16) (a) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033.
(b) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (c) Farina,
V.; Krishnan, B.; Marshall, D. R.; Roth, G. P. J. Org. Chem. 1993, 58,
5434. (d) Farina, V. In ComprehensiVe Organometallic Chemistry II; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, U.K., 1995;
Vol. 12, Chapter 3.4. (e) Casado, A. L.; Espinet, P. J. Am. Chem. Soc.
1998, 120, 8978.
(17) Pilcher, G.; Skinner, H. A. In The Chemistry of the Metal-carbon
Bond; Hartley, F. R., Patai, S., Eds.; Wiley: Chichester, U.K., 1982; Vol.
1; Chapter 2; p 68 (b) O’Neill, M. E.; Wade, K. In ComprehensiVe
Organometallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W.,
Eds.; Pergamon: Oxford, U.K., 1982; Vol. 1, Chapter 1, p 8.
(18) (a) Carmalt, C. J.; Norman, N. C.; Clarkson, L. M. In ComprehensiVe
Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Eds.; Pergamon: Oxford, U.K., 1995; Vol. 1, Chapter 12, p 566. (b)
Marshall, J. A.; Grant, C. M. J. Org. Chem. 1999, 64, 696 and references
therein.
Acknowledgment. We are grateful to Xunta de Galicia
(XUGA 10305A98) and the University of A Corun˜a for
financial support. I.P. also acknowledges a predoctoral
fellowship from Xunta de Galicia.
Supporting Information Available: Experimental pro-
cedures and relevant spectral data for compounds 3-7. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL990939T
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