Electrosynthesis of Heterocyclic Compounds by Radical Cyclization in Environmentally Friendly Media

Wednesday, 27 May 2015: 09:05
PDR 5 (Hilton Chicago)
J. P. Mendes (Centro de Química, Universidade do Minho), J. M. S. S. Esperança (Universidade Nova de Lisboa), A. P. Esteves, M. M. Silva, and M. J. Medeiros (Centro de Química, Universidade do Minho)
The formation of carbon-carbon bonds by radical cyclisation has become an important tool for the synthesis of natural products containing heterocyclic rings [1].  The majority of radical cyclisations in heterocyclic chemistry are still carried out using tributyltin hydride as the reducing agent. This has disadvantages, as the tributylin hydride is toxic and it is difficult to completely remove the tin species from the reaction mixture.

The electrochemical version of similar intramolecular processes - in reactions involving aryl or vinyl bromides [2], bromoacetals [2], or α-bromoamides [2] with double or triple bonds in the presence of nickel(II) complexes as catalysts - has been shown to be highly efficient.  The reaction can be performed under mild conditions using relatively simple equipment. It also avoids the hazardous or toxic reagents used in the tributyltin hydride method.

Although most of the reactions have been reported in aprotic solvents, their toxicity, hazards and cost make them unattractive.  This makes the search for non-toxic fluid alternatives highly desirable.  

Ionic liquids (ILs) represent a class of alternative solvents currently receiving serious consideration, as they have environmental and technological benefits [3].   Their characteristics render them promising replacements for volatile organic solvents (VOCs).

As an extension of our previous research, we undertake further studies on analogs/derivatives of bromopropargyl esters as substrates. In the present work, we investigate the reductive intramolecular cyclization of bromopropargyl ethers derivatives,  catalysed by electrogenerated (1,4,8,11-tetramethyl-1,4,8,11-tetraaza-cyclotetradecane)nickel(I), [Ni(tmc)]+ as the catalysts in N,N,N-trimethyl-N-(2-hydroxyethyl)ammonium bis(trifluoromethylsulfonyl)imide,[N1 1 1 2(OH)][NTf2] and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C2mim][NTf2] by cyclic voltammetry and controlled-potential electrolysis.  The results show that the reaction leads to the formation of the expected cyclic compounds, which are important intermediates in the synthesis of natural products with possible biological activities [4]. 



 We are grateful to the Fundação para a Ciência e Tecnologia (PestC/QUI/UI0686/2013 and FCOMP-01-0124-FEDER-037302) for financial support of this work.


1. B. Giese, “Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds”, Pergamon Press, Oxford (1986).

2. E. Dunach, M.J. Medeiros, S. Olivero, New J. Chem., 30, 1534 (2006).

3. Ionic liquids IIIB: Fundamentals, Process, Challenges, and Opportunities, ACS Symp. Ser. (Eds.: R. D. Rogers and K. R. Seddon), ACS, Washington DC, 2005.

4. P.K. Mandal, G. Maiti, S.C. Roy, J. Org. Chem., 63, 2829 (1998).