Scheme 4 Sequential
hydroamination/hydroalkylation
of
phenylacetylene.
Fig. 1 Ortep diagram of compound 5b drawn with 30% probability
We thank DST, New Delhi for financial support to this
work. Dr R. K. Boruah of Analytical Chemistry Division,
NEIST, Jorhat is gratefully acknowledged for single crystal
analysis. RS thanks Council of Scientific and Industrial
Research, New Delhi (India), for the award of a research
fellowship. We also thank the Director, NEIST, Jorhat for his
keen interest and constant encouragement.
ellipsoid.
scope of the reaction was then investigated with a number of
different arylamines as well as terminal alkynes and the results
obtained are summarised in Table 2. Reaction of phenylacetylene
with various arylamines afforded the conjugated ketimines in good
yields (entries 5a–e, Table 2). We next examined the feasibility of
the reaction by employing various aromatic alkynes having
mono-, di- and tri-substituents and were pleased to find that
smooth reaction occurred with comparable yields (entries 5g–k,
Table 2). Aliphatic alkyne was also found to undergo the
transformation, albeit with a lower yield (entry 5f, Table 2).
However, some uncharacterised compounds were detected in all
cases. All the products obtained were characterized by IR, NMR
and mass spectrometry. Additionally, the structure of compound
5b was confirmed by X-ray single crystal analysis (Fig. 1). However,
an attempt to recover and reuse the catalyst failed, probably
because of the formation of the uncharacterized products.
Although mechanistic studies are not performed, the
formation of the conjugated ketimine product can be rational-
ised by an initial hydroamination of the alkyne followed by a
second hydroalkylation step as shown in Scheme 4. To confirm
the role of indium in the second hydroalkylation step of the
reaction, we further reacted phenylacetylene with pre-formed
imine 3c generated from hydroamination of phenylacetylene
with p-toluidine. Reaction of 3c with two equivalents of
phenylacetylene in the presence of 10 mol% of In(OTf)3 under
refluxing toluene led to the formation of product 5a with minor
improvement in yield as compared to the three component
reaction. When the reaction is performed in the absence of
the indium catalyst, no conversion of the reactants to the
desired product was detected. This shows that indium is
essential for the second hydroalkylation step to take place
and the reaction follows an intermolecular pathway.
Notes and references
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In summary, we have developed the first protocol for direct
intermolecular hydroamination/hydroalkylation of terminal
alkynes under one-pot conditions. In(OTf)3 is shown to
effectively act as a double catalyst for sequential hydro-
amination and hydroalkylation of terminal alkynes in the
absence of any other additive and/or co-catalyst. A range of
arylamines and alkynes were studied and good yields of the
products were obtained. This methodology offers a new
approach for the synthesis of conjugated ketimines from
simple starting materials with excellent atom-economy.
10 C. Vaxelaire, P. Winter and M. Christmann, Angew. Chem., Int.
Ed., 2011, 50, 3605.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 9525–9527 9527