3748
K. Murai et al. / Tetrahedron Letters 53 (2012) 3746–3749
O
H2NNH2•H2O
N
4a 96%
4b 56%
nBu
nBu
HN
N
SMe
NH2
HN
O
nBu
O
O
N
OMe
see
N
N
N
Table 3
N
O
O
MeS
1d
2dd
NH2
O
OMe
O
N
nBu
4c 80%
N
CO2Me
Scheme 2. Derivation of benzisoxazole 2dd.
valuable from the viewpoint of divergent molecule synthesis, be-
cause these functions are useful intermediates particularly for
the preparation of various heterocyclic compounds.13 The phenyl-
ethynyl magnesium bromide was first tested, but the reaction did
not proceed even at room temperature due to the lack of reactivity
of alkynyl Grignard reagents (entry 1). On the other hand, alkynyl
lithium reagents gave good results. They were found to react with
the heterocyclic esters smoothly to produce alkynyl ketone deriv-
atives (entries 2–8). Importantly, esters of isoxazoline 1a and ben-
zisoxazole 1d along with that of the isoxazole 1c participate
efficiently in this process.
The synthetic utility of this transformation and the versatility of
the alkynyl ketone moiety were demonstrated by the several trans-
formations of alkynyl ketone 2dd (Scheme 2). Thus, the reaction of
2dd with hydrazine gave pyrazole derivative 4a in good yield.13a
Pyrimidine 4b can also be prepared by the reaction of 2dd with
S-methyl isothiourea.13a Furthermore, the reaction of 2dd with
methyl 3-aminocrotonate leads to the formation of pyridine 4c in
a moderately high yield.13b As described above, the two step pro-
cess, including the introduction of alkynyl group and the derivati-
zation, is very efficient for diverse bis-heterocyclic compounds
from readily available heterocyclic esters.14
References and notes
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In conclusion, we have developed a facile method for the prep-
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Acknowledgments
This work was financially supported by Grant-in-Aid for
Scientific Research (B) and for Young Scientists (B) from the JSPS.
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Supplementary data
7. For the numbering of compounds 2 and 3, the first alphabet shows the kind of
heterocycles and the second alphabet is numbered to each heterocycles in
order.
Supplementary data associated with this article can be found, in