iodides could participate in Suzuki-Miyaura reactions
with aryl or alkenyl organoboron species.11 Such reactions
have almost remained the only illustration of the utility of
cyclopropyl iodides in cross-couplings5c,12 besides an addi-
tional isolated example of a Negishi reaction with an aryl-
zinc, reported during the chemical development of the non-
nucleoside reverse transcriptase inhibitor MIV-150.13
Alkynylcyclopropanes constitute an interesting class of
substituted cyclopropanes which are found in some biologi-
cally active compounds14 and can be involved in synthe-
tically useful transition metal-catalyzed reactions.15 Herein,
we report that a wide variety of functionalized alkynylcy-
clopropanes can be efficiently synthesized by copper-free
Sonogashira cross-coupling between cyclopropyl iodides
and terminal alkynes.
Table 1. Sonogashira Coupling between Phenylacetylene and
cis-2-Iodocyclopropanemethanol 1
a 0.25-0.50 mmol scale. b Determined by analysis of the crude
material by 1H NMR spectroscopy. c Isolated yield of analytically pure
material. d Not determined. Alkynylcyclpropane 2 could not be easily
separated from unreacted 1 by flash chromatography e On a larger scale
(5 mmol), PdCl2(MeCN)2 (1 mol %) and X-Phos (3 mol %) were used.
(6) (a) Hildebrand, J. P.; Marsden, S. P. Synlett 1996, 893–894.
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The cis-2-iodocyclopropanemethanol (1)16 was selected
as a substrate in our initial studies. Attempts to achieve a
Sonogashira coupling between compound 1 and phenyl-
acetylene, employing classical palladium and copper cata-
lysts with an amine, were unsuccessful.17,18 Because the
oxidative addition of the palladium(0) complex into the
cyclopropyl carbon-iodine bond may be difficult, the use
of conditions reported by Buchwald and Gelman for less
reactive substrates, such as aryl chlorides or tosylates, was
considered.19-21 We found that treatment of cyclopropyl
iodide 1 with phenylacetylene (1.5 equiv) in the presence of
PdCl2(MeCN)2 (3 mol %), X-Phos (9 mol %) asthe ligand,
and Cs2CO3 (2.5 equiv) as the base (MeCN, 80 °C, 1.5 h)
afforded the desired alkynylcyclopropane 2 in 93% yield
(Table 1, entry 1). As other palladium complexes and
ligands gave inferior results,22 only the effect of the base
and the solvent was examined. In acetonitrile, Cs2CO3 and
K3PO4 were almost equally efficient but K2CO3 provided
inferior results (Table 1, entries 2 and 3). Interestingly, the
reaction could be run in solvents of lower polarity than
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