Seminar: Carbene or Proton Transfer? – Controlling the Reactivity of Diazoalkanes (Prof. Dr. Rene M. Koenigs)

Tuesday, 18 February 2020 - 12:00pm – Tuesday, 18 February 2020 - 1:00pm  |  ChemSci M11

Abstract

The protonation reaction of diazomethane with carboxylic acids to provide methyl esters is an important reaction with many applications in chemical synthesis. In this textbook example diazomethane reacts as a base in an initial acid-base reaction with the carboxylic acid.[1] A different reactivity mode of diazoalkanes can be accessed using metal catalysts or photochemical conditions, which proceed via metal-carbene or free carbene intermediates.[2]

Herein, we report on our efforts to control the reactivity of diazoalkanes and to harness their reactivity in carbene and proton transfer reactions. We showcase  photochemical carbene transfer reactions, ranging from cycloaddition reactions,[3] ylide formation,[4] and X-H functionalization reactions.[5] We continue with our findings in C-H functionalization reactions that allow the synthesis of pharmaceutically important tryptamine, or gem-difluoro olefins.[6]

We conclude with our latest findings on the reactivity of aryldiazoacetates that form an unreactive hydrogen-bonding complex with mildly acidic alcohols. Upon photoexcitation of this complex, a photoinduced proton transfer occurs that now allows mild O-H functionalization reactions under stoichiometric conditions in high yields.[7]

 

References: 

[1] R. Brückner, Organic Mechanisms: Reactions, Stereochemistry and Synthesis, Springer, 2010, pp. 93.

[2] C. Empel, R. M. Koenigs, Synlett, 2019, 30, 1929.

[3] Selected examples: a) R.Hommelsheim, Y. Guo, Z. Yang, C. Empel, R. M. Koenigs, Angew. Chem. Int. Ed. 2019, 58, 1203; b) F. He, R. M. Koenigs, Chem. Commun. 2019, 55, 4881; c) Y. Guo, T. V. Nguyen, R. M. Koenigs, Org. Lett. 2019, 21, 8814.

[4] Selected examples: a) K. J. Hock, R. M. Koenigs, Angew. Chem. Int. Ed. 2017, 56, 13566; b) C. Empel, K. J. Hock, R. M. Koenigs, Chem. Commun. 2019, 55, 338; S. Jana, Z. Yang, C. Pei, X. Xu, R. M. Koenigs, Chem. Sci. 2019, 10, 10129;c) S. Jana, R. M. Koenigs, Org. Lett. 2019, 21, 3653.

[5] Selected examples: a) C. Empel, F. W. Patureu, R. M. Koenigs, J. Org. Chem. 2019, 84, 11316; b) F. He, F. Li, R. M. Koenigs, J. Org. Chem. 2020, 85, 1240.

[6] Selected examples: a) K. J. Hock, A. Knorrscheidt, R. Hommelsheim, J. Ho, M. J. Weissenborn, R. M. Koenigs, Angew. Chem. Int. Ed. 2019, 58, 3630; b) Z. Yang, M. Möller, R. M. Koenigs, Angew. Chem. Int. Ed. 2020, 10.1002/anie.201915500; c) S. Jana, F. Li, C. Empel, D. Verspeek, P. Aseeva, R. M. Koenigs, Chem. Eur. J. 2020, 10.1002/chem.201904994.

[7] S. Jana., Z. Yang, F. Li, C. Empel, J. Ho, R. M. Koenigs, Angew. Chem. Int. Ed. 2020, 10.1002/anie.201915161.