Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2011, 9, 6484
COMMUNICATION
Highly stereoselective synthesis of tetrasubstituted alkenes via
hydroamination of alkynes and C–H acetoxylation†
Weibing Liu,* Cui Chen and Qing Zhang
Received 14th June 2011, Accepted 13th July 2011
DOI: 10.1039/c1ob05958k
A novel reaction including the sequence of hydroamination
of alkynes and subsequent oxidative C–H bond functionaliza-
tion has been developed in the presence of diacetoxyiodoben-
zene (DIB). The method allows us to synthesize a wide
Scheme 1 The synthesis of tetrasubstituted (E)-alkenes.
range of tetrasubstituted (E)-alkenes and provides a potential
method to construct densely functionalized carbonyl com-
pounds.
time on the model reaction was carried out (see the ESI†). The best
result was obtained in CH2Cl2 in the presence of 1.2 equivalent of
DIB at 0 ◦C for overnight.
Tandem C–C, C–hetero bond formation leading to useful molec-
ular structures is one of the most interesting and challenging
research topics in organic chemistry.1 Indeed, direct oxidative
C–H bond functionalization provides an atom-economical and
efficient pathway to achieve these goals. Representative examples
have been elegantly utilized not only in abundant academic
research studies, but also in the production of a variety of
fine chemicals, such as pharmaceuticals, agrochemicals, and
intermediates.2 Notably, hypervalent iodine compounds, serving
as mild and chemoselective oxidants, have received significant
attention from chemists in recent years owing to their envi-
ronmentally benign nature and ready availability;3 furthermore,
considering the high toxicity of metal oxidants, such as Pb(IV),
Tl(III), and Hg(II),4 hypervalent iodine reagents are considered as
attractive alternatives to those toxic metal oxidants, and they have
been widely applied in synthetic organic chemistry in oxidative
couplings to form novel C–C, C–O, and C–N bonds.5 Recently,
we observed a notable outcome including hydroamination of an
alkyne and subsequent diacetoxyiodobenzene (DIB) mediated C–
H bond acetoxylation, representing an example to construct new
tetrasubstituted (E)-alkenes (Scheme 1). Interestingly, a further
oxidative C–H bond alkoxylation leading to the formation of
densely functionalized b-imino ketones was also disclosed, when
alcohol was introduced into the reaction system. The structures of
product 3aa and 5 have been confirmed by 1H NMR, 13C NMR and
NOE.6
To explore the substrate scope and limitations of this reaction,
a range of electron-deficient alkynes, including alkynones and
alkynoates, and primary alkylamines were then examined under
the optimized reaction conditions. As shown in Scheme 2, all of the
reactions proceeded smoothly and gave the (E)-tetrasubstituted
alkenes exclusively in good to excellent isolated yields. It was found
that the electronic property of the substituents on the alkynes
has little effect on the reaction efficiency (3aa–3ea). In general,
alkylamines react more readily with electron-deficient alkynes un-
der the optimized reaction conditions as compared to arylamines.
Thus, N-alkylated alkenes could be effectively prepared. However,
the reaction between electron-deficient alkynes and arylamines
failed to result in the corresponding alkene products. These results
are attributed to the enhanced nucleophilicity of alkylamines,
which favors hydroamination of the alkynes and the formation
of tetrasubstituted alkenes, and is consistent with the mechanistic
proposal.
Although arylamines were inert under the standard reaction
conditions, earlier reported literature showed that cationic silver
salts can effectively promote the hydroamination of alkynones
and alkynoates to form enamines.7 Enlightened by these elegant
examples, an arylamine was then employed as a coupling partner
and was expected to form N-arylated alkene products. The
catalytic system of AgBF4 (5 mol%)/L-proline(5 mol%) was
utilized in the reaction of ethyl 3-phenylpropiolate and aniline in
CH2Cl2. The resulting mixture was stirred at room temperature
for 30 min, and 1.2 equivalent of DIB was then introduced
into the reaction system at 0 ◦C and stirred overnight. Grati-
fyingly, the result showed that this sequential one-pot reaction
proceeded smoothly and afforded the expected product (E)-ethyl
2-acetoxy-3-phenyl-3-(phenylamino)acrylate (3dh) in 72% isolated
yield.
Initially, we tried to establish an effective reaction system based
on the above-mentioned transformation. A brief optimization
concerning the effects of several organic solvents, temperature and
School of Chemistry and Life Science, Guangdong University of Petro-
chemical Technology, 139 Guangdu Two Road, Maoming 525000, P. R.
China. E-mail: lwb409@yahoo.com.cn; Fax: +86-668-2923575; Tel: +86-
668-2923956
† Electronic supplementary information (ESI) available: Full experimental
details, and copies of NMR spectral data. See DOI: 10.1039/c1ob05958k
Interestingly, b-imino ketones containing a quaternary a-
carbon atom were efficiently obtained when methanol was in-
troduced into the reaction system. For example, the reaction
6484 | Org. Biomol. Chem., 2011, 9, 6484–6486
This journal is
The Royal Society of Chemistry 2011
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Liu, Weibing
