1. Metal-Free Intramolecular Aminocyanation of
Alkenes via N–CN Bond Cleavage
Zhongda Pan
Advisor: Christopher J. Douglas
Department of Chemistry,
University of Minnesota, Minneapolis
ACS Division of Organic Chemistry
2014 Graduate Research Symposium
University of California, Irvine
July 26, 2014
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2. Introduction
Metal-catalyzed  bond activation — a “cut-and-sew” strategy
The concept of ‘cut-and-sew’: Xu, T., Dong, G. Angew. Chem., Int. Ed. 2012, 51, 7567.
Hoang, G. T. Development of New Reaction Methodologies via Transition Metal Catalyzed
Bond Activation Processes. Ph.D. Thesis, University of Minnesota, 2012. 2

3. Introduction
Challenges and strategies of C–C bond activation
Selected reviews on C–C bond activations:(a) Jun, C. H. Chem. Soc. Rev. 2004, 33, 610. (b) Murakami, M.; Makino, M.;
Ashida, S.; Matsuda, T. Bull. Chem. Soc. Jpn. 2006, 79, 1315. (c) Park, Y. J.; Park, J. W.; Jun, C. H. Acc. Chem. Res. 2008, 41,
222. (d) Murakami, M.; Matsuda, T. Chem. Commun. 2011, 47, 1100. (e) Ruhland, K. Eur. J. Org. Chem. 2012, 14, 2683. (f)
Etienne, M.; Weller, A. S. Chem. Soc. Rev. 2014, 43, 242. (g) Dermenci, A.; Coe, J. W.; Dong, G. Org. Chem. Front. 2014, 1,
567. 3

4. Introduction
C–C bond activation and alkene functionalizations
Dreis, A. M.; Douglas, C. J. J. Am. Chem. Soc. 2009, 131, 412. For related mechanistic studies, see: (a) Rathbun,
C. M.; Johnson, J. B. J. Am. Chem. Soc. 2011, 133, 2031. (b) Lutz, J. P.; Rathbun, C. M.; Stevenson, S. M.;
Powell, B. M.; Boman, T. S.; Baxter, C. E. Zona, J. M.; Johnson, J. B. J. Am. Chem. Soc. 2012, 134, 715.
Xu, T., Dong, G. Angew. Chem., Int. Ed. 2012, 51, 7567. 4

5. Introduction
C–CN activation and alkene cyano-functionalizations
Nakao, Y.; Ebata, S.; Yada, A.; Hiyama, T.; Ikawa, M.; Ogoshi, S. J. Am. Chem. Soc. 2008, 130, 12874.
Rondla, N. R.; Ogilvie, J. M.; Pan, Z.; Douglas, C. J. Chem. Commun. 2014, 50, 8974.
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6. Introduction
Oxycyanation: from C–CN to O–CN activation
Koester, D. C.; Kobayashi, M.; Werz, D. B.; Nakao, Y. J. Am. Chem. Soc. 2012, 134, 6544.
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7. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen, A. G.; Taylor, R. J. Chem. Soc. Perkin. Trans. 2, 1997, S1-S19.
Cunningham, I. D.; Light, M. E.; Hursthouse, M. B. Acat Crystallogr., Sect. C: Cryst. Struct. Commun. 1999, 55, 1833.
Vliet, E. B. Org. Synth. 1941, 1, 20.
Introduction
Inspirations
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8. Introduction
Aminocyanation — what’s new?
Leading reviews on alkene difunctionalizations:
(a) Minatti, A.; Muñiz, K. Chem. Soc. Rev. 2007, 36, 1142.
(b) Jensne, K. H.; Sigman, M. S. Org. Biomol. Chem. 2008, 6, 4083.
(c) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011, 111, 2981. 8

9. Results and Discussion
Substrate synthesis
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10. Results and Discussion
Optimization
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11. Results and Discussion
Optimization
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12. Results and Discussion
Substrate scope and limitations
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13. Results and Discussion
Substrate scope and limitations
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14. Results and Discussion
Alternative mechanistic consideration
Yang, Y.; Zhang, Y.; Wang, J. Org. Lett. 2011, 13, 5608.
Anbarasan, P.; Neumann, H.; Beller, M. Chem. Eur. J. 2011, 17, 4217.
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15. Results and Discussion
Alternative mechanistic consideration
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16. Results and Discussion
Double cross-over experiments
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17. Results and Discussion
Alternative mechanistic consideration
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18. More aminocyanations
Nakao group’s aminocyanation
Pan, Z.; Pound, S. M. Rondla, N. R.; Douglas, C. J. Angew. Chem., Int. Ed. 2014, 53, 5170.
Miyazaki,Y.; Ohta, N.; Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 3732.
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19. Evidence for N–CN oxidative addition
More aminocyanations
Miyazaki,Y.; Ohta, N.; Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 3732.
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20. Evidence for N–CN oxidative addition
More aminocyanations
Miyazaki,Y.; Ohta, N.; Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 3732.
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21. Summary and future work
All roads lead to Rome
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22. Summary and future work
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23. Acknowledgement
Christopher Douglas
Sarah Pound
Naveen Rondla
Douglas group members
DOC 2014 Graduate Research Symposium
National Institutes of Health(R01 GM095559)
Douglas group @ Minneapolis
Sculpture Garden, 2013