Tetrahedron Letters
Metal-free hydration of aromatic haloalkynes to
a-halomethyl
ketones
Min Ye a,y, Yuelu Wen a,y, Huifang Li b, Yejuan Fu a, Qinghao Wang a,
⇑
a Key Laboratory of Organo-Pharmaceutical Chemistry of Jiangxi Province, Gannan Normal University, Ganzhou, Jiangxi 341000, PR China
b Laboratory for Computational and Theoretical Chemistry of Advanced Materials Physical Science and Engineering Division, King Abdullah University of Science and
Technology, Thuwal 23955-6900, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly regioselective and efficient metal-free hydration of aromatic haloalkynes to
a-halomethyl
Received 4 August 2016
Revised 12 September 2016
Accepted 27 September 2016
Available online 28 September 2016
ketones using cheap tetrafluoroboric acid as catalyst is described. The protocol is conducted under
convenient conditions and affords products in good to excellent yields, with broad substrate scope,
including a variety of aromatic alkynyl chlorides, alkynyl bromides, and alkynyl iodides.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Metal-free
Hydration
Haloalkyne
a-Halomethyl ketone
Regioselectivity
a
-Halomethyl ketones are one kind of the most important inter-
acidic solvent, which limited their application (Scheme 1, b). Very
recently, Li’s group reported a mild protocol for alkyne hydration
under metal-free conditions.10 Inspired by the work and previous
transformation, here we present the first Brønsted acid catalyzed
mediates and versatile building blocks in organic synthesis, and
their high reactivity makes them easily convert into various of use-
ful compounds.1 Moreover, their derivatives are widely repre-
sented in many natural products and biologically active
hydration of 1-haloalkynes to the corresponding
ketones in trifluoroethanol solvent (Scheme 1, c).
a-halomethyl
molecules.2
a-Halomethyl ketones are commonly prepared from
olefins,3 ketones, and their derivatives with different halogen-
donating agents.4 However, most of the reactions suffered from
one or more drawbacks, such as harsh reactions, hazardous
reagents, nonregiospecific reaction, and overhalogenation.
We began our study by screening the reaction between
(bromoethynyl)benzene 1h and water to obtain the optimal reac-
tion conditions. As shown in Table 1, firstly trifluoroethanol was
chosen as the reaction solvent, and different acids were tried as
catalyst. Both acetic acid and trifluoroacetic acid only gave the pro-
duct in trace yield (Table 1, entries 1 and 2). We were pleased to
find that trifluoromethanesulfonic acid can generate 2h in 35%
yield, a portion of vinyl trifluoromethanesulfinate was detected
except the corresponding product and the raw material with
GC–MS analysis, this showed that trifluoromethanesulfonic acid
can proceed electrophilic addition with haloalkyne (Table 1, entry
3). The yield can be increased to 97% when the reaction time was
extended to 24 h, we speculated that it is advantageous for the
hydrolysis of the vinyl trifluoromethanesulfinate intermediate
(Table 1, entry 4). To our delight, tetrafluoroboric acid can effi-
ciently catalyze the reaction to produce 2h in 95% isolated yield
(Table 1, entry 5). It should be pointed out that tetrafluoroboric
acid cannot be added to triple bond of the haloalkyne for the weak
nucleophile activation of tetrafluoroborate anion. The control
experiment showed that the catalyst was essential for the reaction
(Table 1, entry 6). Then a variety of common solvents were
On the other hand, great achievements have been made for the
synthesis of ketones through catalyzed hydration of alkynes.5 In
sharp contrast, only few examples have been developed for the
hydration of 1-haloalkynes to give
pioneering work, He and co-workers described a gold-catalyzed
a-halomethyl ketones. In a
of 1-bromoalkynes and 1-chloroalkynes to generate the corre-
sponding
reported a AgF/TFA catalyzed hydration of 1-bromoalkynes and
a
-haloketones (Scheme 1, a).6 In 2014, Chen and Liu
1-chloroalkynes to the a
-halomethyl ketones.7 In 2016, He’s group
developed a Cu(OAc)2/TFA catalyzed hydration of 1-haloalkynes.8
In addition, Xiao’s group also reported a similar transformation
through In(OAc)3/HOAc catalytic system.9 Obviously, these
approaches required transition-metal catalysts with or without
⇑
Corresponding author. Tel./fax: +86 797 8393670.
Contribute equally.
y
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.