10.1002/adsc.201800336
Advanced Synthesis & Catalysis
which results in the desired fully substituted 1,2,3-
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triazolyl-4-phosphonate
3
with
high
1,4-
regioselectivity. Intermediates A and E were
confirmed by the mentioned 31P-NMR experiments
(for details, see the SI).
Scheme 5. Proposed Mechanism of the RhAAC Reaction.
In summary, we developed a novel rhodium(I)-
catalyzed azide-alkyne cycloaddition (RhAAC)
reaction of internal alkynylphosphonates for the
highly regioselective synthesis of fully substituted
1,2,3-triazolyl-4-phosphonates under mild conditions.
[Rh(CO)2Cl]2, as the critical catalyst for the RhAAC
reaction, was insensitive to air and water. This
strategy exhibits a broad substrate scope, good
functional group tolerance, high yields and excellent
regioselectivities. The proposed approach provides a
mild and general direct access to various fully
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substituted
internal
1,2,3-triazolyl-4-phosphonates
alkynylphosphonates. The
from
potential
advantages of this RhAAC reaction are the gram-
scale preparation, the application to carbohydrate
synthesis and the solid-phase synthesis of triazolyl-4-
phosphonates. Further mechanistic studies and
advanced theoretical calculations for the transition
states and intermediates of this reaction are being
performed in our laboratory.
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Experimental Section
General procedure for the synthesis of 3a: To a vial
containing [Rh(CO)2Cl]2 (2.0 mg, 0.025 equiv, 0.005
mmol) in DCM (2 mL) under air was added diethyl
(phenylethynyl)phosphonate (47.6 mg, 1 equiv, 0.2 mmol)
and (azidomethyl)benzene (40.2 mg, 1.5 equiv, 0.3 mmol).
It was necessary to add the azides last. The vial was closed
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o
and the mixture was stirred at 40 C for 12 h. The mixture
was purified with flash column chromatography (50%
EtOAc in petroleum ether) to give the pure product (66 mg,
89%) as a yellow oil.
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Acknowledgments
This work was supported by grants from the Doctoral Program
Foundation of Liaoning Province (Nos. 20170520378,
20170520274), the Fundamental Research Funds for the Central
Universities (Nos. DUT16RC(3)114, DUT18LK25) and the
National Natural Science Foundation of China (Nos. 21702025,
51703018). We thank Prof. Baomin Wang (Dalian University of
Technology) for his enthusiastic assistance.
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