10.1002/anie.201709571
Angewandte Chemie International Edition
[9] N. Tewari, N. Dwivedi, R. Tripathi, Tetrahedron Lett. 2004, 45,
9011−9014.
reducing agents that activate reagents via single-electron transfer
manifolds while undergoing a homolytic cleavage to generate C(sp3)-
centered radicals. This light-triggered dual-reactivity profile was
integrated into a nickel catalytic cycle to enable C(sp2)–C(sp3) cross-
coupling reactions without the need for an external photoredox
catalyst. We are conducting ongoing studies to further exploit the
photochemical activity of alkyl-DHPs in other radical-based carbon-
carbon bond-forming processes.
[10] Our attempts to perform Stern-Volmer quenching studies using
different electron acceptors, including the electron-poor cyano
substrate 2a, met with failure. For all the tested 4-alkyl-1,4-
dihydropyridines, including 1a, we observed an increase of
fluorescence intensity upon multiple irradiation of the substrate alone.
This phenomenon is likely ascribable to the formation of a strongly
emitting compound, which is generated upon photo-degradation of 1.
This emission behavior, which is further detailed in the Supporting
Information (Section B4, Figure S6), precluded a reliable quenching
measurement.
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
[11] K. H. Kim, X. Bai, R. C. Brown, J. Anal. Appl. Pyrolysis, 2014, 110,
254–263.
Keywords: cross-coupling • dihydropyridines • nickel catalysis •
photochemistry • synthetic methods
[12] For selected examples, see: a) C. Pac, A. Nakasone, H. Sakurai, J. Am.
Chem. Soc. 1977, 99, 5806−5808; b) R. M. Borg, D. R. Arnold, T. S.
Cameron, Can. J. Chem. 1984, 62, 1785−1802; c) M. Mella, M.
Fagnoni, A. Albini, J. Org. Chem. 1994, 59, 5614−5622; d) A.
McNally, C. K. Prier, D. W. C. MacMillan, Science 2011, 334, 1114–
1117.
[1] a) V. Balzani, P. Ceroni, A. Juris, in Photochemistry and Pho-
tophysics, Wiley-VCH, 2014; b) P. Klán, J. Jacob, in Photochemistry
of Organic Compounds, John Wiley & Sons, 2010.
[2] A. Albini, M. Fagnoni, in Handbook of Synthetic Photochemistry,
Wiley-VCH, 2010.
[3] N. J. Turro, V. Ramamurthy, J. C. Scaiano, in Modern Molecular
Photochemistry of Organic Molecules, University Science Books,
Sausalito, CA, 2010; Chapter 7.
[13] a) P. McDevitt, B. M. Vittimberga, J. Heterocyclic Chem. 1990, 27,
1903–1908; b) J. D. Bagnato, W. W. Shum, M. Strohmeier, D. M.
Grant, A. M. Arif, J. S. Miller, Angew. Chem. Int. Ed. 2006, 45, 5322–
5326; Angew. Chem. 2006, 118, 5448–5452.
[14] S. Z. Tasker, E. A. Standley, T. F. Jamison, Nature 2014, 509, 299–
309.
[4] a) M. Silvi, E. Arceo, I. D. Jurberg, C. Cassani, P. Melchiorre, J. Am.
Chem. Soc. 2015, 137, 6120–6123; b) G. Filippini, M. Silvi, P.
Melchiorre, Angew. Chem. Int. Ed. 2017, 56, 4447–4451; Angew.
Chem. 2017, 129, 4518–4522; c) M. Silvi, C. Verrier, Y. P. Rey, L.
Buzzetti, P. Melchiorre, Nat. Chem. 2017, 9, 868–873; d) G. Filippini,
M. Nappi, P. Melchiorre, Tetrahedron 2015, 71, 4535–4542.
[5] C. Zheng, S.-L. You, Chem. Soc. Rev. 2012, 41, 2498–2518.
[6] a) S. Fukuzumi, K. Hironaka, T. Tanaka, J. Am. Chem. Soc. 1983,
105, 4722–4727; b) J. Jung, J. Kim, G. Park, Y. You, E. J. Cho, Adv.
Synth. Catal. 2016, 358, 74–80; c) M. A. Emmanuel, N. R. Greenberg,
D. G. Oblinsky, T. K. Hyster, Nature 2016, 540, 414–417; d) L. I.
Panferova, A. V. Tsymbal, V. V. Levin, M. I. Struchkova, A. D.
Dilman, Org. Lett. 2016, 18, 996–999; e) W. Chen, H. Tao, W.
Huang, G. Wang, S. Li, X. Cheng, G. Li, Chem. Eur. J. 2016, 22,
9546–9550.
[15] M. H. Shaw, J. Twilton, D. W. C. MacMillan, J. Org. Chem. 2016, 81,
6898–6926.
[16] For a review: a) J. Twilton, C. Le, P. Zhang, M. H. Shaw, R. W.
Evans, D. W. C. MacMillan, Nat. Rev. Chem. 2017, 1, 0052. For
selected examples of synergistic nickel/photoredox catalysis, see: b) J.
C. Tellis, D. N. Primer, G. A. Molander, Science 2014, 345, 433−436;
c) Z. Zuo, D. T. Ahneman, L. Chu, J. A. Terrett, A. G. Doyle, D. W.
C. MacMillan, Science 2014, 345, 437−440; d) V. Corcé, L.-M.
Chamoreau, E. Derat, J.-P. Goddard, C. Ollivier, L. Fensterbank,
Angew. Chem. Int. Ed. 2015, 54, 11414–11418; Angew. Chem. 2015,
127, 11576–11580; e) M. Jouffroy, D. N. Primer, G. A. Molander, J.
Am. Chem. Soc. 2016, 138, 475–478.
[17] 4-Alkyl-1,4-dihydropyridines were recently used as alkyl radical
precursors in nickel-catalyzed cross-coupling reactions; the reported
methods, however, require the use of an external iridium-based
photoredox catalyst, see Refs. [7b,d].
[18] a) P. Johnston, R. T. Smith, S. Allmendinger, D. W. C. MacMillan,
Nature 2016, 536, 322–325; b) M. Durandetti, M. Devaud, J.
Perichon, New J. Chem. 1996, 20, 659–667.
[19] The use of a LED strip (λmax = 405 nm) severely reduced the reactivity
of the nickel cross-coupling reaction. Details of the importance of the
light intensity and the use of HP LEDs are reported in Section D2
within the Supporting Information.
[20] Previous methods required the use of an external photoredox catalyst
and alkyltrifluoroborates as radical precursors, see: a) J. Amani, E.
Sodagar, G. A. Molander, Org. Lett. 2016, 18, 732–735; b) J. Amani,
G. A. Molander, J. Org. Chem. 2017, 82, 1856–1863.
[7] For examples of 4-alkyl-1,4-dihydropyridines serving as radical
precursors under the action of external photoredox catalysts, see: a) K.
Nakajima, S. Nojima, K. Sakata, Y. Nishibayashi, ChemCatChem
2016, 8, 1028–1032; b) A. Gutierrez-Bonet, J. C. Tellis, J. K. Matsui,
́
́
B. A. Vara, G. A. Molander, ACS Catal. 2016, 6, 8004−8008; c) W.
Chen, Z. Liu, J. Tian, J. Ma, X. Cheng, G. Li, J. Am. Chem. Soc. 2016,
138, 12312–12315; d) K. Nakajima, S. Nojima, Y. Nishibayashi,
Angew. Chem. Int. Ed. 2016, 55, 14106–14110; Angew. Chem. 2016,
128, 14312–14316. For a review, see: e) W. Huang, X. Cheng, Synlett
2017, 28, 148–158.
[8]
A. Gutierrez-Bonet, C. Remeur, J. K. Matsui, G. A. Molander, J. Am.
́
́
Chem. Soc. 2017, 139, 12251–12258.
4
This article is protected by copyright. All rights reserved.