Nucleophilic C(sp2)-H Bond Functionalization in Heteroarоmatics as an Atom- and Stage-Efficient Synthetic Tool to Obtain Novel Heterocyclic Derivatives

Mikhail Varaksin m.v.varaksin@urfu.ru 1,2 Oleg Chupakhin 1,2 Valery Charushin 1,2
1Department of Organic and Biomolecular Chemistry, Ural Federal University, Ekaterinburg
2Laboratory of Heterocyclic Compounds, Institute of Organic Synthesis, Ekaterinburg

Two principal approaches to modify heteroaromatics by means of incorporation of a nucleophilic fragment through displacement of the C-H bond will be considered.

The first one is based on catalytic activation of the C-H bond. It involves the step of deprotonation followed by the formation of organometallic intermediates, which then react with nucleophiles into the final products (1).

The second approach suggests a direct nucleophilic attack at unsubstituted carbon of an heteroaromatic ring leading to the σH-adducts followed by either two electrons oxidation (“Addition-Oxidation” Protocol 2.1) or elimination of good-leaving group (“Addition-Elimination” Protocol 2.2).1,2

Both schemes involve the departure of proton, however the sequence and the ways of activations differ.

It has been well documented that the metal-free coupling reactions provide a good complementary basis for metal-catalysed cross-coupling reactions, as illustrated by many examples from the chemistry of biologically active compounds, macrocyclic derivatives, polymers, free stable radicals, metallocenes, carboranes, etc.3-7

  1. Charushin, V.N.; Chupakhin, O.N., Eds. Metal Free C-H Functionalization of Aromatics. Nucleophilic Displacement of Hydrogen. In Top Heterocyclic Chemistry, Maes, B. U. W., Cossy, J., Poland, S., Series Eds.; Springer: Heidelberg, New York, Dordrecht, London, 2014; Vol. 37.
  2. Chupakhin, O.N.; Charushin, V.N. Tetrahedron Lett. 2016, 57, 2665−2672.
  3. Varaksin, M.V.; Chupakhin, O.N.; Charushin, V.N. et al. J. Org. Chem. 2012, 77, 9087.
  4. Varaksin, M.V.; Chupakhin, O.N.; Charushin, V.N. et al. Macroheterocycles 2013, 6, 308.
  5. Chupakhin, O.N.; Varaksin, M.V. et al. J. Org. Chem. 2009, 74, 2870.
  6. Utepova, I.A.; Chupakhin, O.N.; Charushin, V.N. et al. J. Org. Chem. 2014, 79, 8659.
  7. Varaksin, M.V.; Chupakhin, O.N.; Charushin, V.N. et al. Organometallics 2015, 34, 5285.

The study was supported by the RSF (Project № 14-13-01177) and the RFBR (Project № 16-03-00958).

Mikhail Varaksin
Dr. Mikhail Varaksin
Ural Federal University








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