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Green Chemistry
Page 5 of 7
DOI: 10.1039/C8GC01180J
Journal Name
COMMUNICATION
When the coupling reaction of 1a and 2a was conducted in the
presence of radical trapping agent 2,2,6,6- tetramethylpiperidine 1-
oxyl (TEMPO, 50 mol%) under the optimized condition (eqn. 4), the
formation of 2-(phenylethynyl)pyridine was totally inhibited,
indicating that a radical intermediate might be involved in this
coupling reaction.2h
centered radicals, leads to the formation of the product 3a. The
intermediate 11 was caught by ESI mass measurements. (see SI for
details of ESI measurements).
Conclusions
In summary, we have significantly demonstrated the visible-light-
initiated copper(I) catalysed denitroginative coupling of 2-
hydrazinopyridine with terminal alkynes to form 2-(alkyl/aryl or
heteroarylethynyl)pyridine. This coupling reaction includes a SET
process with O2, followed by copper(II)-superoxo or -peroxo
complex assisted N2 elimination. This is the first report of N2
elimination (cleavage of non-activated C-N bond) at room
temperature. This photochemical process works well for a wide
range of substrates (42 examples), forms N2 and water as benign
by-products, uses simple CuCl as catalyst, O2 as an oxidant, readily
available substrates as starting materials, mild reaction conditions
and applicable for the synthesis of potent mGluR5 noncompetitive
antagonists MPEP and M-MPEP. In addition, the green chemistry
metrics and the overall reaction cost evaluation signify that the
process is green and highly cost efficient. Thus, this method is a
simple, green and effective approach for the synthesis of 2-
(alkyl/arylethynyl) pyridine.
Scheme 2. Control experiments for the formation of 2-
(phenylethynyl)pyridine under the standard condition.
Acknowledgements
This work was supported by the Ministry of Science and
Based on these above control experiments and our previous
studies2c,d,e, a reaction mechanism was proposed and shown in
Scheme 3. Photo excitation (λabs= 474 nm) of in situ generated
copper(I) phenylacetylide (2a’) generates a long lived triplet photo
excited copper(I) phenylacetylide (7)10 (see Figure S1 for IR
spectrum of 2a’, and Figure S4 for UV-visible spectra of 2a’), which
then undergoes a SET process by donating an electron to O2,
generating the intermediates Cu(II)-phenylacetylide (8) and a
superoxide radical anion11, as evidenced by EPR measurements12
(see the SI, Figure S2).
Technology, Taiwan.
Conflicts of interest
There are no conflicts to declare.
Notes and references
1
C.K. Prier, D.A. Rankic and D.W.C. Mackmillan, Chem. Rev.,
2013, 113, 5322.
2
Our previously reported works and the references therein,
see; (a) A. Sagadevan and K. C. Hwang, Adv. Synth. Catal.,
2012, 354, 3421; (b) A. Sagadevan, A. Ragupathi and K. C.
Hwang, Photochem. Photobiol. Sci., 2013, 12, 2110; (c) A.
Sagadevan, A. Ragupathi, C. –C.Lin, J. R. Hwu and K. C.
Hwang, Green Chem., 2015, 17, 1113; (d) A. Sagadevan, A.
Scheme 3. Proposed reaction mechanism.
Ragupathi and K. C. Hwang, Angew. Chem., Int. Ed., 2015, 54
,
13896; (e) A. Ragupathi, A. Sagadevan, C. C. Lin, J. R. Hwu
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Sagadevan, P. C. Lyu and K. C. Hwang, Green Chem, 2016, 18
4526; (g) A. Sagadevan, V. P. Charpe, and K. C. Hwang, Catal.
Sci. Technol. 2016, , 7688; (h) A. Sagadevan, V. P. Charpe, A.
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6
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3
4
a) K. Ouyang, W. Hao, W. X, Zhang and Z. Xi, Chem. Rev.,
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Next, the nucleophilic addition of 2-hydrazinopyridine(1a) to Cu(II)
phenylacetylide (8) results in the formation of the complex Cu(III)
(9) species.2c,e,13 Reductive elimination of Cu(III) to Cu(I) generates
the intermediate 10.2c,e Residual 2-hydrazinopyridine (act as a
bidentate ligand) coordinates to CuI and its reaction with molecular
oxygen leads to the formation of bidentate chelated copper(II)
superoxo/-peroxo complex (A)2e,14,15, which can abstract the acidic
protons from the intermediate 10 to form 11. N2 elimination of the
intermediate 11, followed by recombination of sp2 and sp C-
(a) M-K. Zhu, J. F. Zhao and T. P. Loh, Org.lett., 2011, 13
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6308; (b) H. Zhang, C. Wang, Z. Li and Z. Wang, Tetrahedron.
Lett., 2015, 56, 5371; (c) J. B. Liu, H-P. Zhou and Y. Y. Peng,
Tetrahedron. Lett., 2014, 55, 2872; (d) Z. Peng, G. Hu, H.
Qiao, P. Xu, Y. Gao and Y. Zhao, J. Org. Chem., 2014, 79
,
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