Synthetic and mechanistic aspects of cross-coupling of nitroxyl radicals of 3-imidazoline series with terminal alkynes Sergei F. Vasilevsky a, * , Olga L. Krivenko a , Vitalii R. Gorelik b , Igor V. Alabugin c, * a Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russian Federation b International Tomography Center, Novosibirsk, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russian Federation c Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306, United States article info Article history: Received 29 January 2008 Received in revised form 20 June 2008 Accepted 24 June 2008 Available online 27 June 2008 Keywords: Nitronylnitroxyl radicals (NNR) Terminal alkynes Copper salts of alkynes Cross-coupling Homocoupling 3-Imidazolyl-3-oxide-1-oxyls Transition metal catalysis abstract Practical synthetic approaches to the new class of acetylenic derivatives of 3-imidazolyl-3-oxide-1-oxyls, including biradicals, were developed through cross-coupling reactions of 3-imidazolyl halides with either terminal alkynes or their copper salts. The presence of nitroxyl functional group as an internal oxidant leads to a competition between the formation of cross-coupling products and the products of oxidative homocoupling. The balance in this competition can be shifted toward the cross-coupling products through the combination of factors that includes nature of the catalyst, reactivity of the halides, and reaction conditions. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Stable nitroxyl radicals continue to draw significant attention of researchers working at the interface between chemistry, physics, and biology. Traditionally, radicals of this family have been widely used as spin probes in biochemistry 1 and in the design of para- magnetic complexes in coordination chemistry. 2 New areas of application for these molecules continue to emerge, most recently in studies of intricate details of intramolecular interactions and spin catalysis. 3,4 Stringent requirements to structural, electronic, and steric pa- rameters often complicate development of new materials with designed magnetic and optical properties. In this context, radicals with ethynyl moieties are promising because the HChC-group is a rigid, convenient scaffold for construction of spin-labeled mole- cules with programmable electronic, geometric, and magnetic parameters. On one hand, increased acidity of the methine protons allows facile functionalization of such molecules through the cre- ation of new C–C bonds. On the other hand, the –ChC-linkage ensures the rigid spatial arrangement of functional moieties and can participate in electron delocalization. Both of these factors are often important for studies of magnetic and optical properties. If needed, partial hydrogenation of the ChC-bond allows one to prepare the respective cis- and trans-alkene derivatives in trans- formations, which change molecular geometry but preserve con- jugation. Another valuable property of alkyne functionality is its ability to undergo facile cycloaddition reactions 5–7 useful for the attachment of spin labels to biomolecules. Finally, full hydrogena- tion of the triple bond can be used to drastically decrease the ex- change interaction. For example, this problem had to be addressed in the studies of the fundamental aspects of spin catalysis in re- combination of spin-correlated ion-radical pairs. In these studies, hydrogenation of acetylenic derivatives of nitroxyl radicals of 2-imidazolyl family permitted for the first time detection of the magnetic effect (15%) in recombination of ion-radical pairs. 3 However, more detailed quantitative studies required the further decrease in the exchange interaction between the spin center and the ion-radical pair. Such decrease could be achieved in nitroxyls of 3-imidazolyl family where the paramagnetic center is separated from the aromatic molecule with two single bonds. It is important to emphasize that although chemistry of 3-imi- dazolylnitroxyls is well-developed, information regarding synthe- sis of acetylenic derivatives with this core has not been available before the initiation of our research program in this field. From our point of view, this situation is not due to the lack of interest to * Corresponding authors. Fax: þ1 7 383 3307350 (S.F.V.). E-mail addresses: vasilev@kinetics.nsc.ru (S.F. Vasilevsky), alabugin@chem.fsu. edu (I.V. Alabugin). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2008.06.088 Tetrahedron 64 (2008) 8807–8814