Tetrahedron Letters
Sonogashira cross-coupling in a designer ionic liquid (IL) without
copper, external base, or additive, and with recycling and reuse of the
IL
⇑
A. Srinivas Reddy, Kenneth K. Laali
Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Application of a piperidine-appended dimethyl-imidazolium-NTf2 ionic liquid as dual solvent and base in
the Sonogashira cross-coupling reaction of aryl-iodides with terminal acetylenes under mild conditions
has been demonstrated. The method employs PdCl2(PPh3)2 without copper and external base. It is
applicable to the synthesis of SF5-substituted diaryl- and aryl-alkyl-acetylenes, and can also be utilized
for efficient homo-coupling of terminal acetylenes under aerobic conditions. The potential for recycling
and reuse of this designer-IL offers an added advantage.
Received 6 May 2015
Revised 11 June 2015
Accepted 22 June 2015
Available online 26 June 2015
Keywords:
Ó 2015 Elsevier Ltd. All rights reserved.
Sonogashira cross coupling
Piperidine-tethered imidazolium-NTf2
Designer-IL
Synthesis of SF5-substituted diarylethynes
Homo-coupling of alkynes
Recycling and reuse of IL
The Sonogashira cross-coupling reaction is a powerful method
for the synthesis of internal alkynes and enynes. This highly
versatile Csp2–Csp bond forming protocol is widely exploited in
the synthesis of natural products, pharmaceuticals, agrochemicals,
and materials. The reactions are typically carried out by using
catalytic amounts of palladium (most commonly Pd(Ph3P)2Cl2)
along with a copper halide (typically CuI) in the presence of an
amine, used either as solvent or as cosolvent along with solvents
such as DMF, THF, or toluene. Both homogeneous and heteroge-
neous Sonogashira coupling have been extensively studied, and
progress in this ever expanding research area has been summa-
rized in timely reviews.1–5
Research aimed at: (a) replacing Pd for the more readily avail-
able, cheaper metals, (b) copper-free conditions, (c) avoiding the
use of large quantities of base, (d) replacing solvents such as
DMF and DMSO with environmentally more acceptable alterna-
tives, and (e) minimizing competing formation of homocoupling
products, constitute active areas that are under continuous devel-
opment. Along these lines, ligand-free Fe/Cu co-catalyzed
Sonogashira coupling reactions have been reported by using
Fe(acac)3/CuI and Fe2O3/Cu(acac)2.6,7 These methods still require
base and are typically performed at high temperatures in DMF or
DMSO. By using PdCl2 along with a water soluble phosphine
ligand,8 or by employing Pd-nanoparticles9, the coupling reaction
could be carried out in water/amine mixtures. Competing homo-
coupling was greatly lowered by performing the reaction in
Pd(Ph3P)2Cl2/CuI/TEA/MeCN under reflux and by working under
H2 + N2 atmosphere.10 Efficient homocoupling of terminal alkynes
was reported with Pd(OAc)2/DABCO/CuI/air/MeCN,11 or via
a
Cu(I)-catalyzed method employing CuCl/O2 together with an
amine ligand (TMEDA, DBEDA, DABCO) in MeCN as solvent.12
Ionic liquids (ILs) have shown promise as versatile media for
various Pd-catalyzed reactions including Sonogashira.13 Apart from
[BMIM][PF6],14–16 phosphonium type amino acid-ILs,17 and
biodegradable ILs18 have been employed along with the Pd
catalyst [Pd(OAc)2, PdCl2, or Pd(Ph3P)2Cl2, or a phosphine-ligated
Pd-complex] together with a base (TEA, iPr2NH, or piperidine).
The copper-free Sonogashira reaction employed ultrasound,15 or
a phosphine-ligated Pd-complex.18
A basic-IL with appended iPr2N-groups was previously used
in representative C–C bond forming reactions including
Sonogashira.19 The method utilized Pd(Ph3P)2Cl2 along with
piperidine or methanol and was accompanied by noticeable
homocoupling (10–40%).
In continuation of our previous studies on metal-mediated
transformations in ILs,20 and in connection to our continuing inter-
est in the synthesis of SF5-aromatics,21 we report here on the appli-
cation of a piperidine-appended dimethyl-imidazolium-NTf2 IL-1
acting as dual solvent and base in the Sonogashira cross-coupling
⇑
Corresponding author. Tel.: +1 904 620 1503; fax: +1 904 620 3535.
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.