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. 2021 Mar 5;12(15):5450-5457.
doi: 10.1039/d1sc00943e.

Photoactive electron donor-acceptor complex platform for Ni-mediated C(sp3)-C(sp2) bond formation

Lisa Marie Kammer  1 , Shorouk O Badir  1 , Ren-Ming Hu  1 , Gary A Molander  1
Affiliations

Photoactive electron donor-acceptor complex platform for Ni-mediated C(sp3)-C(sp2) bond formation

Lisa Marie Kammer et al. Chem Sci. .

Abstract

A dual photochemical/nickel-mediated decarboxylative strategy for the assembly of C(sp3)-C(sp2) linkages is disclosed. Under light irradiation at 390 nm, commercially available and inexpensive Hantzsch ester (HE) functions as a potent organic photoreductant to deliver catalytically active Ni(0) species through single-electron transfer (SET) manifolds. As part of its dual role, the Hantzsch ester effects a decarboxylative-based radical generation through electron donor-acceptor (EDA) complex activation. This homogeneous, net-reductive platform bypasses the need for exogenous photocatalysts, stoichiometric metal reductants, and additives. Under this cross-electrophile paradigm, the coupling of diverse C(sp3)-centered radical architectures (including primary, secondary, stabilized benzylic, α-oxy, and α-amino systems) with (hetero)aryl bromides has been accomplished. The protocol proceeds under mild reaction conditions in the presence of sensitive functional groups and pharmaceutically relevant cores.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. (A) Strategies toward net-reductive decarboxylative-based cross-couplings. (B) Overview of electron donor–acceptor (EDA) photoactivation. (C) Electron donor–acceptor (EDA) complex platform for Ni-mediated alkyl transfer using HE as an organic photoreductant.
Scheme 2
Scheme 2. Scope of the developed C(sp3)–C(sp2) cross-coupling. All values correspond to isolated yields after purification. Reaction conditions as depicted in Table 1, entry 1 (0.5 mmol scale).
Fig. 1
Fig. 1. (A) Visual appearance of reaction components and mixtures thereof. (B) UV/vis absorption spectra measured in DMA (0.1 M) unless otherwise noted. Ni complex = NiBr2(dtbpy), aryl bromide = 4-bromobenzonitrile, and RAE = cyclohexyl-N-hydroxyphthalimide ester. Mixture refers to a DMA solution of all reaction components. (C) Benesi–Hildebrand plot. (D) Job plot for a mixture of N-(cyclohexyl)-hydroxyphthalimide ester (2) and HE in DMA (0.2 M).
Scheme 3
Scheme 3. (A) Investigation of HE as electron donor. (B) Mechanistic experiments. [a]Isolated yield on 0.3 mmol scale, [b]analysed via GC-MS analysis, [c]NMR yield, *1.0 equiv. of 42. (C) Proposed mechanism.
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References

    1. For selected examples see:

    2. Jana R. Pathak T. P. Sigman M. S. Chem. Rev. 2011;111:1417–1492. - PMC - PubMed
    3. Gildner P. G. Colacot T. J. Organometallics. 2015;34:5497–5508.
    4. Johansson Seechurn C. C. C. Kitching M. O. Colacot T. J. Snieckus V. Angew. Chem., Int. Ed. 2012;51:5062–5085. - PubMed
    5. Campeau L.-C. Hazari N. Organometallics. 2019;38:3–35. - PMC - PubMed
    6. Choi J. Fu G. C. Science. 2017;356:7230. - PMC - PubMed
    7. Gu J. Wang X. Xue W. Gong H. Org. Chem. Front. 2015;2:1411–1421.
    8. Hu X. Chem. Sci. 2011;2:1867–1886.
    9. Kaga A. Chiba S. ACS Catal. 2017;7:4697–4706.
    10. Ma X. Murray B. Biscoe M. R. Nat. Rev. Chem. 2020;4:584–599. - PMC - PubMed
    11. Weix D. J. Acc. Chem. Res. 2015;48:1767–1775. - PMC - PubMed

    1. For selected examples see:

    2. Everson D. A. Shrestha R. Weix D. J. J. Am. Chem. Soc. 2010;132:920–921. - PubMed
    3. Everson D. A. Weix D. J. J. Org. Chem. 2014;79:4793–4798. - PMC - PubMed
    4. Gu J. Qiu C. Lu W. Qian Q. Lin K. Gong H. Synthesis. 2017;49:1867–1873.
    5. Yu X. Yang T. Wang S. Xu H. Gong H. Org. Lett. 2011;13:2138–2141. - PubMed
    6. Woods B. P. Orlandi M. Huang C.-Y. Sigman M. S. Doyle A. G. J. Am. Chem. Soc. 2017;139:5688–5691. - PubMed
    7. Jin Y. Yang H. Wang C. Org. Lett. 2019;21:7602–7608. - PubMed
    8. Kadunce N. T. Reisman S. E. J. Am. Chem. Soc. 2015;137:10480–10483. - PMC - PubMed
    9. Knappke C. E. I. Grupe S. Gärtner D. Corpet M. Gosmini C. Jacobi von Wangelin A. Chem.–Eur. J. 2014;20:6828–6842. - PubMed
    10. Moragas T. Correa A. Martin R. Chem.–Eur. J. 2014;20:8242–8258. - PubMed
    11. Tian Z.-X. Qiao J.-B. Xu G.-L. Pang X. Qi L. Ma W.-Y. Zhao Z.-Z. Duan J. Du Y.-F. Su P. Liu X.-Y. Shu X.-Z. J. Am. Chem. Soc. 2019;141:7637–7643. - PubMed
    12. Cherney A. H. Reisman S. E. J. Am. Chem. Soc. 2014;136:14365–14368. - PMC - PubMed
    13. Huihui K. M. M. Caputo J. A. Melchor Z. Olivares A. M. Spiewak A. M. Johnson K. A. DiBenedetto T. A. Kim S. Ackerman L. K. G. Weix D. J. J. Am. Chem. Soc. 2016;138:5016–5019. - PMC - PubMed

    14. ; for selected examples using electrochemical methods, see:

    15. Li H. Breen C. P. Seo H. Jamison T. F. Fang Y.-Q. Bio M. M. Org. Lett. 2018;20:1338–1341. - PMC - PubMed
    16. Koyanagi T. Herath A. Chong A. Ratnikov M. Valiere A. Chang J. Molteni V. Loren J. Org. Lett. 2019;21:816–820. - PubMed

    17. ; for cross-electrophile coupling in biological environments, see:

    18. Flood D. T. Asai S. Zhang X. Wang J. Yoon L. Adams Z. C. Dillingham B. C. Sanchez B. B. Vantourout J. C. Flanagan M. E. Piotrowski D. W. Richardson P. Green S. A. Shenvi R. A. Chen J. S. Baran P. S. Dawson P. E. J. Am. Chem. Soc. 2019;141:9998–10006. - PMC - PubMed

    1. For selected examples on decarboxylative arylation using carbon preformed nucleophiles, see:

    2. Chen T.-G. Zhang H. Mykhailiuk P. K. Merchant R. R. Smith C. A. Qin T. Baran P. S. Angew. Chem., Int. Ed. 2019;58:2454–2458. - PMC - PubMed
    3. Cornella J. Edwards J. T. Qin T. Kawamura S. Wang J. Pan C.-M. Gianatassio R. Schmidt M. Eastgate M. D. Baran P. S. J. Am. Chem. Soc. 2016;138:2174–2177. - PMC - PubMed
    4. Liu X.-G. Zhou C.-J. Lin E. Han X.-L. Zhang S.-S. Li Q. Wang H. Angew. Chem., Int. Ed. 2018;57:13096–13100. - PubMed
    5. Toriyama F. Cornella J. Wimmer L. Chen T.-G. Dixon D. D. Creech G. Baran P. S. J. Am. Chem. Soc. 2016;138:11132–11135. - PMC - PubMed
    1. Buskes M. J. Blanco M.-J. Molecules. 2020;25:3493. - PMC - PubMed
    1. Kuroboshi M. Waki Y. Tanaka H. Synlett. 2002;2002:0637–0639.
    2. Kuroboshi M. Waki Y. Tanaka H. J. Org. Chem. 2003;68:3938–3942. - PubMed