Tetrahedron Letters 48 (2007) 7088–7090
Copper catalyzed regioselective coupling of allylic halides and
alkynes promoted by weak inorganic bases
Lothar W. Bieber* and Margarete F. da Silva
Departamento de Quı´mica Fundamental, Universidade Federal de Pernambuco, Recife PE 50-670-901, Brazil
Received 18 July 2007; revised 30 July 2007; accepted 1 August 2007
Available online 7 August 2007
Abstract—Allylic halides and terminal alkynes couple under CuI catalysis in DMSO or DMF solution. In most cases, sodium car-
bonate or bicarbonate is sufficient to promote the reaction; less reactive alkynes require catalytic amounts of DBU. Bifunctional
alkynes and halides can be reacted selectively according to the stoichiometry used. Trimethylsilyl, hydroxyl, ester and halide groups
are tolerated in the alkyne. Most halides react without allylic rearrangement. The method is suitable for the synthesis of function-
alized enynes.
Ó 2007 Elsevier Ltd. All rights reserved.
Most of C–C bond forming reactions by nucleophilic
substitution involve carbanionic species or organometal-
lic reagents and have been performed traditionally in
anhydrous organic solvents. Only during the past two
decades numerous examples of such transformations
have been reported to occur in the presence of water
or even in completely aqueous medium.1 An early pre-
cursor of the actual aqueous methodologies was the ally-
lation of terminal alkynes performed in a water/diethyl
ether system using tertiary amines as base, but only
alkynols and simple allylic and propargylic halides gave
interesting preparative yields.2 A somewhat more gen-
eral method has made use of triethylamine as solvent
and was successful also with phenyl acetylene.3 The
introduction of inorganic bases4 and aprotic polar sol-
vents5,6 brought further improvement in the yields, but
the scope of these couplings remained restricted to sim-
ple allylic halides and mostly unfunctionalized alkynes
or alkynols. Other limitations were long reaction times
and the need for an inert atmosphere. During our
studies on the reactivity of terminal acetylenes towards
unusual electrophiles such as diphenyl dichalcogenides7
or iminium ions8 under protic conditions we found
that the allylation reaction can also be performed under
very mild conditions in the presence of moisture and
oxygen.
Starting with allyl bromide and phenyl acetylene we ob-
served that the reaction was complete after stirring for
4 h in commercial, undried DMSO at room tempera-
ture, using 0.02 equiv of copper iodide as catalyst and
potassium carbonate as base (Table 1, entry 1). 1-Hex-
yne showed much lower reactivity in the same reaction,
but addition of a catalytic amount of DBU promoted a
quantitative allylation in the same delay (entry 2). Alky-
nols reacted under similar conditions and with excellent
yields, in the case of propargyl alcohol even in pure
water as solvent (entries 5–7). Examining other func-
tionalized alkynes, we obtained excellent results with tri-
methylsilyl acetylene and ethyl propiolate, whose
saponification was minimized using potassium bicar-
bonate as base (entries 3 and 4). In these and the follow-
ing examples the addition of solid sodium sulfite was
useful to suppress some oxidative dimerization and to
produce the coupling products in high yield and purity.
Under similar controlled conditions, but in DMF as sol-
vent, even propargyl chloride could be allylated at the
terminal acetylenic carbon producing a reagent suitable
for further substitution reactions (entry 8). Use of
1,4-diethynyl benzene in appropriate stoichiometries
allowed selective mono- or diallylation in high yields
(entries 9 and 10).
Keywords: Allylation; Functionalized alkynes; Aprotic solvent; In-
organic bases; Selectivity.
*
After these encouraging results with allyl bromide, higher
allylic halides were used under similar conditions.
Corresponding author. Tel.: +55 81 21268440; fax: +55 81
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.08.010
Bieber, Lothar W.
