TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4597–4599
General synthesis of alkyl phenyl selenides from organic halides
mediated by zinc in aqueous medium
Lothar W. Bieber,* Ana C. P. F. de Sa´, Paulo H. Menezes and Simone M. C. Gonc¸alves
Departamento de Qu´ımica Fundamental, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil
Received 21 March 2001; accepted 3 May 2001
Abstract—Organic halides of different structural types react with diphenyl diselenide and zinc dust in aqueous medium to give
alkyl phenyl selenides. Benzylic and allylic bromides, a-bromoesters, acids and ketones and some primary alkyl iodides produce
high yields even under acidic conditions. Less reactive halides need basic medium. The reaction proceeds equally well in the
presence of various unprotected functional groups. Control experiments support a SH2 mechanism via alkyl radicals. © 2001
Elsevier Science Ltd. All rights reserved.
Alkyl phenyl selenides are versatile intermediates in
organic synthesis especially for the mild introduction of
CꢀC double bonds.1 Several general and high yielding
preparative methods have been developed using
reagents such as phenyl selenol or diphenyl diselenide 1
in nucleophilic displacement reactions. In the first case,
a phenyl selenolate anion reacts with organic halides or
sulfonates, in the second the same species is the leaving
group displaced by enolates. Both procedures require
basic conditions and the second one has to be per-
formed under strictly anhydrous conditions limiting
thus the scope to base resistant substrates. Alterna-
tively, there are several recent reports of Chinese scien-
tists dealing with the reaction of diselenides with
bromoketones,2 bromoesters,3 allyl,4 propargyl4 and
benzyl5 bromides promoted by In, Sn, Cd and Zn in
neutral aqueous media. Although satisfactory yields of
the corresponding mixed selenides have been obtained
in several examples, these special procedures could not
be extended to other classes of halides; furthermore, the
use of In and Cd in preparative scale is not advisable
for economical and environmental reasons. We present
here a simple, general and high yielding preparation of
alkyl phenyl selenides using commercial zinc dust in
aqueous medium.
stabilized intermediates and are highly efficient in
aqueous Barbier-type reactions.6–8 First attempts under
similar conditions using monobasic or dibasic phos-
phate solutions without any cosolvent led exclusively to
reduction of the halide leaving diphenyl diselenide (1)
unchanged. Addition of acetonitrile or dioxane to dis-
solve 1 circumvented this problem; complete consump-
tion of the reagents was observed in a few minutes and
high yields of phenylselenyl-substituted compounds 3
were obtained in both acidic and basic medium. A great
number of structurally different halides was reacted
under these two standard conditions (Table 1). In con-
centrated dibasic potassium phosphate solution (pHꢀ
12), alkyl halides gave good to excellent yields (entries
1–4); acidic, neutral or strongly basic conditions low-
ered the yield, except for secondary iodides which gave
best results in KOH solution (entries 5 and 6). With
tertiary alkyl halides (R=t-butyl and adamantyl,
entries 7–9) only modest yields were obtained under
these conditions, but the use of large excess of t-butyl
iodide improved the yield significantly even in this case.
More reactive halides such as ethyl iodide, allyl and
benzyl bromide and several a-haloesters, acids, nitriles
and ketones gave high yields even in monobasic sodium
phosphate solution (pHꢀ4). In contrast to Barbier-
type additions to carbonyl compounds6 and Wurtz-type
couplings,9 substituted allylic and propargylic halides
produced exclusively the unrearranged isomers (entries
12–17, 28, 29). In some cases chlorides gave better
yields than bromides, probably because the latter were
too reactive and reduction became predominant under
basic conditions (entries 12 versus 13, 15 versus 16, 18
versus 19, 20 versus 21 and 28 versus 29). A similar
reasoning may explain the advantage to use granulated
We started our experiments with a-bromoesters, allylic
and benzylic halides which can react through resonance
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00820-6