COMMUNICATION
The conversion of organic halides to organometallics by
direct metal insertion (the Grignard reaction) is a very gen-
eral method. The LiCl-mediated insertion of Mg,[1] Zn,[2]
Al,[3] Mn,[4] and In[5] has proven to be especially effective
and provides access to a range of functionalized organome-
tallic reagents that can readily be applied to cross-coupling[6]
and other reactions with electrophiles.[7] Nevertheless, some
functionalized halides, such as 4-bromobenzonitrile (1a), do
not insert magnesium under standard conditions and require
specific optimization because of radical side-reactions. Takai
tablished Pd-catalyzed cross-couplings with organoindium
reagents.[11] Interestingly, a Pd-catalyzed cross-coupling of
tri(4-cyanophenyl)indium (2a) with the Buchwald ligand (2-
dicyclohexylphosphino-2’,6’-dimethoxybiphenyl (S-Phos))[12]
led to a smooth reaction with ethyl 4-bromobenzoate (1b;
THF, 508C, 12 h), providing the desired biphenyl 3a in 71%
yield. Ethyl 4-iodobenzoate (1c) was also used instead of 1b
as an electrophile, which resulted in an increased yield of 3a
(81%; Scheme 1).
Herein, we report that this method is general and applies
to aryl, heteroaryl, and alkyl bromides, as well as benzyl
chlorides. In all cases, the resulting indium reagents react
with aryl halides in the presence of a palladium catalyst
(Scheme 2).
and Ikawa first reported the beneficial effect of indiumACHTUNTRGNEUNG(III)
halides on the insertion of aluminum metal into allylic hal-
ides.[8] This observation solved the problem of the erratic be-
havior of the direct insertion of magnesium into the bromo-
nitrile 1a and led us to develop a new, general one-pot pro-
cedure for the preparation of triorganoindium compounds
of type 2, 5, 8, and 11, starting from various organic halides
(chlorides and bromides).
Organoindium compounds are versatile organometallic in-
termediates for organic synthesis because they display a
high functional group tolerance and are mainly prepared by
transmetalation reactions.[9] A direct insertion of indium
powder is only possible with activated organic halides and
requires a large excess of this expensive metal.[5,10] However,
the treatment of 1a (1.00 equiv) with magnesium turnings
(2.50 equiv) in the presence of LiCl (2.50 equiv) and InCl3
(0.33 equiv) at room temperature in THF for 4 h leads to
the corresponding triorganoindium reagent (2a) in good
Scheme 2. Preparation of triorganoindium reagents by means of Mg in-
sertion in the presence of LiCl and InCl3. X=Br, Cl; Y=Br, I; R=aryl,
heteroaryl, benzyl, alkyl; E=aryl, heteroaryl; FG=functional group;
[Pd]=PdACHTUNGTRNNEUG(OAc)2 (2%), S-Phos (4%) or [PdCl2AHCTUNTGERN(NUGN PPh3)2] (4%); DMAC=
N,N-dimethylacetamide. [a] Complexed LiCl and magnesium halides are
omitted for clarity.
Therefore, ethyl 4-bromobenzoate (1b) could also be
smoothly converted to the corresponding triarylindium re-
agent, 2b, in 4 h at 258C with Mg/LiCl (2.5 equiv) and InCl3
(0.33 equiv). Subsequent cross-coupling with 3-iodobenzoni-
trile (1d) or 4-bromoanisole (1e; Table 1, entries 1 and 2, re-
yield (77%; Scheme 1). No excess of indium
ACHUTGTNREN(NUG III) is necACHTUNTGRENeNUGN s-
ACHTUNGTRENNUNG
matographic analysis showed complete conversion and more
importantly the absence of significant amounts of side prod-
ucts. Sarandeses and co-workers pioneered and further es-
spectively) in THF at 508C with PdACTHNUTRGNENUG(OAc)2 (2%) and S-Phos
(4%),[12] as the catalytic system, led to the corresponding bi-
phenyl, 3b or 3c, in 57–67% yield after 12 h. Moreover,
tri(4-chlorophenyl)indium 2c could be efficiently prepared
À
by a selective insertion of Mg into the C Br bond of 1-
bromo-4-chlorobenzene (1 f) and was coupled to bromoben-
zocaine (1g) in 82% yield (Table 1, entry 3). The electron-
rich tri(para-anisyl)indium (2d) and tri(ortho-dimethylami-
nophenyl)indium (2e) were also accessible from substrates
1e and 1i under mild conditions (258C, 4 h) and underwent
cross-couplings with 4-iodonitrobenzene (1h) and 1a in 69–
84% yield (Table 1, entries 4 and 5, respectively). Moreover,
tri{[(diethylcarbamoyl)oxy]phenyl}indium (2 f) was prepared
from the corresponding bromoarene (1j) and could be re-
acted with 1a, the bromobenzamide (1k), or the unprotect-
ed bromoindole (4a) in 64–87% yield (Table 1, entries 6–8)
Scheme 1. Preparation of tri(4-cyanophenyl)indium (2a) from 4-bromo-
benzonitrile (1a) by means of Mg insertion in the presence of LiCl and
InCl3 and subsequent Pd-catalyzed cross-coupling. [a] Complexed LiCl
and magnesium halides are omitted for clarity.
under the coupling conditions developed (PdACTHNURGTNEUNG(OAc)2/S-Phos;
THF, 508C). In several cases, it was found that a smaller
amount of magnesium turnings (1.5 instead of 2.5 equiv)
lead to similar results (Table 1, entries 6–8).
The method could also be applied to the preparation of
heteroaromatic indium reagents. Thus, 3-bromopyridine
(4b) was reacted with Mg turnings, LiCl, and InCl3 (1.50,
1.50, and 0.33 equiv, respectively) at 258C in THF and after
4 h full conversion to the corresponding organometallic re-
agent (5a) was detected by GC-MS analysis of a reaction
[a] Dr. S. Bernhardt,+ Z.-L. Shen,+ Prof. Dr. P. Knochel
Department Chemie, Ludwig-Maximilians-Universitꢁt Mꢂnchen
Butenandtstrasse 5–13, Haus F, 81377 Mꢂnchen (Germany)
Fax : (+49)89-2180-77680
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
Chem. Eur. J. 2013, 19, 828 – 833
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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