Page 7 of 8
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
5
the C1 pz-orbital contribution to 65.8%, which is a complete
inversion of what was found in the cyanoalkyne substrate.
Energetically, C3-TS2 is 5.7 kcal/mol higher in energy than A3-
TS1. Thus, the process leading to the preference for the
cyanoalkyne reactant in the competition experiment discussed
above is also applicable when thioalkyne and cyanoalkyne
substrates compete. However, because the thioalkyne is more
reactive, reflected in a barrier of cycloaddition that is ~2
kcal/mol lower than what was found for the terminal alkyne,
thioalkyne cyclization is not entirely dominated by the
cyanoalkyne reaction and minor amounts of thioalkyne
cyclization products can be found in the competition reactions.
457.
DOI: 10.1039/D0OB00579G
6
7
8
J. E. Hein and V. V. Fokin, Chem. Soc. Rev., 2010, 39, 1302.
M. Meldal and C. W. Tornøe, Chem. Rev., 2008, 108, 2952.
C. W. Tornøe, C. Christensen and M. Meldal, J. Org. Chem.,
2002, 67, 3057.
V. V. Rostovtsev, L. B. Green, V. V. Fokin and K. B. Sharpless,
Angew. Chem., Int. Ed., 2002, 41, 2596.
9
10 P. Liu, R. J. Clark and L. Zhu, J. Org. Chem., 2018, 83, 5092.
11 P. Destito, J. R. Couceiro, H. Faustino, F. López and J. L.
Mascareñas, Angew. Chem., Int. Ed., 2017, 56, 10766.
12 J. R. Johansson, T. Beke-Somfai, A. S. Stalsmeden and N. Kann,
Chem. Rev., 2016, 116, 14726.
13 S. Ferrini, J. Z. Chandanshive, S. Lena, M. Comes Franchini, G.
Guanyin, A. Tafi and M. Taddei, J. Org. Chem., 2015, 80, 2562.
14 J. R. Johansson, P. Lincoln, B. Norden and N. Kann, J. Org.
Chem., 2011, 76, 2355.
15 B. C. Boren, S. Narayan, L. K. Rasmussen, L. Zhang, H. Zhao, Z.
Lin, G. Jia and V. V. Fokin, J. Am. Chem. Soc., 2008, 130, 8923.
16 L. Zhang, X. Chen, P. Xue, H. H. Y. Sun, I. D. Williams, K. B.
Sharpless, V. V. Fokin and G. Jia, J. Am. Chem. Soc., 2005, 127,
15998.
17 W. Song, N. Zheng, M. Li, J. He, J. Li, K. Dong, K. Ullah and Y.
Zheng, Adv. Synth. Catal., 2019, 361, 469.
18 W. Song, N. Zheng, M. Li, K. Ullah and Y. Zheng, Adv. Synth.
Catal., 2018, 360, 2429.
19 W. Song, N. Zheng, M. Li, K. Dong, J. Li, K. Ullah and Y. Zheng,
Org. Lett., 2018, 20, 6705.
20 Y. Liao, Q. Lu, G. Chen, Y. Yu, C. Li and X. Huang, ACS Catal.,
2017, 7, 7529.
21 R. Chen, L. Zeng, Z. Lai and S. Cui, Adv. Synth. Catal., 2019, 361,
989.
Conclusions
Nickel-catalyzed cycloaddition of organic azides and
unsymmetrical alkynes was accomplished. The competing click
chemistry was successfully established in a controlled and
protection-group-free manner, featuring high levels of regio-
and chemoselectivity, good functional group tolerance and mild
reaction conditions. DFT calculations show that the cyclization
step is the most demanding and rate-determining step. Ni-
catalyst is capable of enhancing the electronic differences of the
alkyne substrates by binding them via an oxidative addition
process to the nickel center, leading to the reactivity- and
selectivity preferences.
22 W. Song and N. Zheng, Org. Lett., 2017, 19, 6200.
23 S. Ding, G. Jia and J. Sun, Angew. Chem., Int. Ed., 2014, 53,
1877.
24 Q. Luo, G. Jia, J. Sun and Z. Lin, J. Org. Chem., 2014, 79, 11970.
25 E. Rasolofonjatovo, S. Theeramunkong, A. Bouriaud, S.
Kolodych, M. Chaumontet and F. Taran, Org. Lett., 2013, 15,
4698.
26 W. G. Kim, M. E. Kang, J. B. Lee, M. H. Jeon, S. Lee, J. Lee, B.
Choi, P. M. S. D. Cal, S. Kang, J.-M. Kee, G. J. L. Bernades, J.-U.
Rohde, W. Choe and S. Y. Hong, J. Am. Chem. Soc., 2017, 139,
12121.
27 N. Münster, P. Nikodemiak and U. Koert, Org. Lett., 2016, 18,
4296.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This research was supported by the National Research
Foundation of Korea (NRF) Grant (2018M1A2A2063341) funded
by the Ministry of Science and ICT & Future Planning. M.-H.B.
acknowledges support from Institute for Basic Science (IBS-R10-
A1) in Korea.
28 R. R. Ramsubhag and G. B. Dudley, Org. Biomol. Chem., 2016,
14, 5028.
29 M. Z. C. Hatit, C. P. Seath, A. J. B. Watson and G. A. Burley, J.
Org. Chem., 2017, 82, 5461.
30 I. E. Valverde, F. Lecaille, G. Lalmanach, V. Aucagne and A. F.
Delmas, Angew. Chem., Int. Ed., 2012, 51, 718.
31 V. Aucagne and D. A. Leigh, Org. Lett., 2006, 8, 4505.
32 C. P. Seath, G. A. Burley and A. J. B. Watson, Angew. Chem.,
Int. Ed., 2017, 56, 3314.
33 M. Z. C. Hatit, J. C. Sadler, L. A. McLean, B. C. Whitehurst, C. P.
Seath, L. D. Humphreys, R. J. Young, A. J. B. Watson and G. A.
Burley, Org. Lett., 2016, 18, 1694.
34 A. A. Kislukhin, V. P. Hong, K. E. Breitenkamp and M. G. Finn,
Bioconjugate Chem., 2013, 24, 684.
35 Z. Yuan, G.-C. Kuang, R. J. Clark and L. Zhu, Org. Lett., 2012,
14, 2590.
36 R. Chung, A. Vo, V. V. Fokin and J. E. Hein, ACS Catal., 2018, 8,
7889.
37 P. W. N. M. van Leeuwen, P. C. J. Kamer, J. N. H. Reek and P.
Dierkes, Chem. Rev., 2000, 100, 2741.
38 R. G. Parr and Y. Weitao, Density-Functional Theory of Atoms
and Molecules, Oxford University Press, New York, 1994.
39 Y. Zhao and D. G. Truhlar, Theor. Chem. Acc., 2008, 120, 215.
Notes and references
1
(a) N. A. Afagh and A. K. Yudin, Angew. Chem., Int. Ed., 2010,
49, 262; (b) B. M. Trost, Angew. Chem., Int. Ed., 1995, 34, 259.
(a) N. De and E. J. Yoo, ACS Catal., 2018, 8, 48;
(b) P. P. Painter, R. P. Pemberton, B. M. Wong, K. C. Ho and D.
J. Tantillo, J. Org. Chem., 2014, 79, 432; (c) B. Engels and M.
Christl, Angew. Chem., Int. Ed., 2009, 48, 7968; (d) K. N. Houk,
J. Sims, C. R. Watts and L. J. Luskus, J. Am. Chem. Soc., 1973,
95, 7301.
2
3
4
(a) C. Wang, D. Ikhlef, S. Kahlal, J.-Y. Sailard and D. Astruc,
Coord. Chem. Rev., 2016, 316, 1. (b) B. Heller and M. Hapke,
Chem. Soc. Rev., 2007, 36, 1085; (c) Y. Ni and J. Montgomery,
J. Am. Chem. Soc., 2006, 128, 2609; (d) P. A. Evans, J. E.
Robinson, E. W. Baum and A. N. Fazal, J. Am. Chem. Soc., 2002,
124, 8782; (e) M. Lautens, W. Klute and W. Tam, Chem. Rev.,
1996, 96, 49.
A. Marrocchi, A. Facchetti, D. Lanari, S. Santoro and L. Vaccaro,
Chem. Sci., 2016, 7, 6298.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins