Communications
DOI: 10.1002/anie.200802292
Functionalized Indium Reagents
Preparation of Aryl and Heteroaryl Indium(III) Reagents by the Direct
Insertion of Indium in the Presence of LiCl**
Yi-Hung Chen and Paul Knochel*
Dedicated to Professor Rolf Huisgen
Functionalized organometallic compounds are key intermedi-
ates in organic synthesis.[1] In particular, organozinc reagents
are compatible with a wide range of functional groups and
have broad application in synthesis.[2] However, sensitive
functional groups, such as aldehyde or ketone functionalities
with a acidic hydrogen atoms, are only tolerated in special
cases.[3] Furthermore, the reactivity of unsaturated zinc
reagents toward acidic hydrogen atoms of alcohols and
Scheme 1. Preparation of organoindium reagents 1 through direct
indium insertion in the presence of LiCl,followed by palladium-
catalyzed cross-coupling. FG=functional group.
phenols precludes the performance of Negishi cross-coupling
reactions[4] of aromatic iodides containing these functional-
ities. In contrast to organozinc reagents, organoindium
reagents have been shown to be compatible with water and
several important functionalities.[5] However, in classical
syntheses of these organoindium compounds through Li/In
or Mg/In transmetalation, the corresponding organometallic
precursors require protecting groups. Recently, we reported
that LiCl accelerates dramatically the insertion of zinc[6] or
magnesium[7] into organic halides. Herein, we report a
preparation of polyfunctional aryl and heteroaryl indium(III)
reagents 1 through the direct insertion of indium metal in the
presence of LiCl into iodides 2. To the best of our knowledge,
only allyl, propargyl,[5] pentafluorophenyl,[8] and benzyl
indium(III) reagents[9] have been prepared by the direct
treatment of the corresponding halides with indium metal.
Commercially available indium does not react with aryl
iodides. However, when LiCl (2–4 equiv)[10] was added to
indium powder (2–4 equiv) that had been activated with
1,2-dibromoethane and TMSCl[11] in THF, an efficient inser-
tion occurred within 20 min to 24 h at 30–508C to provide
polyfunctional aryl and heteroaryl indium(III) species 1 in
70–97% yield (Scheme 1).
Similarly, the iodoketones 2b and 2c were converted into the
corresponding keto-substituted indium derivatives 1b (508C,
24 h) and 1c (358C, 2h) in 93 and 90% yield, respectively.
The functionalized aryl iodides 2d–g with an ester or
aldehyde functionality also reacted smoothly with indium
metal in the presence of LiCl to give the organoindium(III)
reagents 1d–g in 70–86% yield. The presence of an electron-
withdrawing group or metalation-directing group increased
the insertion rate considerably.
This method was extended to the preparation of hetero-
aryl indium(III) reagents. Heterocyclic iodides (and a heter-
ocyclic bromide), some of which contained a ketone, alde-
hyde, or ester functionality, reacted smoothly with indium
powder in the presence of LiCl to furnish the heteroaryl
indium(III) compounds 1h–m in 78–97% yield (Table 1,
entries 8–13). This method provides access to organoindium
reagents containing a range of important and sensitive
functional groups that are not compatible with organozinc
reagents.
Thus, the treatment of 4-iodoacetophenone (2a) with
activated indium powder (4 equiv) in the presence of LiCl
(4 equiv) in THF at 508C for 24 h provided the desired aryl
indium(III) reagent 1a in 96% yield, as indicated by iodolysis
(Table 1).[12] No insertion occurred in the absence of LiCl.
Organoindium species are useful reagents in organic
synthesis.[5] Palladium-catalyzed cross-coupling reactions with
triorganoindium compounds[13] were pioneered by Sarandeses
and co-workers.[13a] Typically, the cross-coupling reactions are
conducted in THFat reflux. Under these conditions, the cross-
coupling of the less reactive functionalized aryl indium(III)
reagents 1a–m was inefficient. However, upon the addition of
N-methylpyrrolidinone (NMP) as a cosolvent (NMP/THF
1:2),[14] the cross-coupling reactions proceeded smoothly in
the presence of [Pd(dppf)Cl2][15] at 25–668C (dppf =
1,1’-bis(diphenylphosphanyl)ferrocene).
[*] Dr. Y.-H. Chen,Prof. Dr. P. Knochel
Ludwig-Maximilians-Universität München
Department Chemie
Butenandtstrasse 5–13,Haus F,81377 München (Germany)
Fax: (+49)892-1807-7680
E-mail: paul.knochel@cup.uni-muenchen.de
This Pd-catalyzed cross-coupling procedure proved to be
quite general: A range of aryl iodides 3 reacted with the
functionalized organoindium compounds 1 to afford products
of type 4 (Table 2). [Pd(dppf)Cl2], a catalyst developed by
Hayashi et al.,[15] catalyzed these cross-coupling reactions
effectively (Table 2, entries 1, 2, 6, 7, and 9–11). In the case of
[**] Y.-H.C. thanks the Alexander von Humboldt Foundation for financial
support. We thank the Fonds der Chemischen Industrie,the DFG,
Chemetall GmbH (Frankfurt),and BASF AG (Ludwigshafen) for
financial support.
Supporting information for this article is available on the WWW
7648
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 7648 –7651