Tetrahedron Letters
Reactions of tertiary propargyl alcohols with sodium halides under
oxidative conditions
⇑
Marwa M. Aborways, Wesley J. Moran
Department of Chemistry, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The study of the reactions of tertiary propargyl alcohols with sodium halides under oxidative conditions
Received 16 January 2014
Revised 4 February 2014
Accepted 13 February 2014
Available online 25 February 2014
is presented. With sodium iodide,
the -haloenones were only formed in low yields under anhydrous conditions. Conversely, upon addition
of water to the reaction mixtures, -dibromoketones and -dichloroketones were formed in good
yields, but -diiodoketones were not observed.
a-iodoenones were formed, however, with sodium bromide or chloride
a
a
,
a
a,a
a,a
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Halogenation
Propargyl alcohols
Oxidation
Synthesis
A wide range of halogenation reactions can be readily achieved
through treatment of the substrate with the elemental halogen,
that is iodine, bromine, chlorine, or fluorine,1 or by addition of
reagents such as N-iodo-, N-bromo-, or N-chlorosuccinimide.2
These reactants work very well in many cases, but each has
drawbacks such as toxicity, corrosiveness, ease-of-use, relative
high cost, low atom efficiency, or supply issues. Consequently,
the ability to use cheap, readily available, and easy-to-handle
inorganic halides in electrophilic halogenation reactions is a useful
addition to the synthetic tool box and several research groups have
reported examples of this recently.3
3 equiv m-CPBA
O
R
1.5 equiv Cl3CCO2H
I
HO
R
1 equiv NaI, MeCN, rt
n
n = 1, 2, 3, 4
n
1
2
, 61-85%
Scheme 1. Hypoiodous acid induced rearrangement of propargyl alcohols to
a-
iodoenones.
(Table 1, entry 1). Replacing NaI with NaBr led to low conversion
to the analogous -bromoenone 3a and a small amount of another
compound, which was subsequently identified as -dibromoke-
tone 4a (entry 2). Li et al. reported a similar process to form
Substituted propargyl alcohols are readily prepared from
aldehydes/ketones and terminal alkynes and are useful and versa-
tile synthetic intermediates.4 We previously reported that tertiary
a
a,a
a,a-
propargyl alcohols 1 undergo rearrangement to
a-iodoenones 2
dihaloketones catalyzed by FeCl3 with either N-bromosuccinimide
or N-chlorosuccinimide as the halogen source.6 At this point, a sys-
tematic study of the reaction conditions was initiated: varying the
oxidant identified Oxone to be superior (entry 3), while the use of
other oxidants, solvents, and acids led to inferior results (entries 4–
15). Unfortunately, a pure sample of 3a could not be obtained by
chromatography as impurities including 4a could not be fully sep-
arated. We envisaged that adventitious water was responsible for
the formation of compound 4, however, all attempts to eliminate
water from the reaction mixture to preclude its formation were
unsuccessful. Running the reaction in a 1:1 mixture of acetonitrile
and water led to a cleaner reaction, but compound 4 became the
sole product in 63% yield (entry 16). Repeating the reaction with-
out the acid successfully yielded the product, however, slightly
upon treatment with sodium iodide under oxidative conditions
(Scheme 1).5 We postulated that under acidic conditions, hypoio-
dous acid was generated which induced the rearrangement to occur
through iodination of the alkyne.
We were interested in studying whether this rearrangement
process would occur with sodium bromide or sodium chloride, in
place of sodium iodide, under similar conditions to those we
previously identified. Carrying out the reaction with NaI and
m-chloroperbenzoic acid in the presence of trichloroacetic acid in
acetonitrile led to the expected
a-iodoenone 2a in 75% yield
⇑
Corresponding author. Tel.: +44 (0)1484 473741.
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Aborways, Marwa M.
