Cyclohexane and Benzene Amination by Catalytic Nitrene Insertion into C-H Bonds with the Copper-Homoscorpionate Catalyst Tp Br3 Cu(NCMe) M. Mar Dı ´az-Requejo, † Toma ´ s R. Belderraı ´n, † M. Carmen Nicasio, † Swiatoslaw Trofimenko, ‡ and Pedro J. Pe ´ rez* ,† Departamento de Quı ´mica y Ciencia de Materiales, UniVersidad de HuelVa, Campus de El Carmen, 21071-HuelVa, Spain, and Department of Chemistry and Biochemistry, UniVersity of Delaware, Newark, Delaware 19716 Received July 4, 2003; E-mail: perez@dqcm.uhu.es One of the most interesting reactions to functionalize a carbon- hydrogen bond consists of the catalytic formation of an amine by means of the formal insertion of a nitrene group into such unit, in the so-called amination reaction (eq 1). This methodology has been known for years since the seminal work by Breslow and co- workers, 1 that demonstrated the capabilities of the Cytochrome P450 for the tosylamidation of cyclohexane, that is, the insertion of a NTs fragment (Ts ) p-tolylsulfonyl) into a C-H bond. Motherwell et al. 2 later reported the use of ferrous chloride as the catalyst for this transformation. The yields in both cases were low, but these reactions heralded the opening of a new field in the area of C-N bond formation. In recent years, impressive results have been obtained by Che and co-workers, 3 showing the capabilities of ruthenium porphyrins for the tosylamination reaction. Other manganese-, 4 cobalt-, 5 rhodium- 6 or copper-based 7 systems have also been reported to induce this insertion reaction. However, most of these results supposed the transfer of a nitrene group from iminoiodanes of formula PhIdNR to substrates that contain a somewhat activated carbon-hydrogen bond (Scheme 1): allylic or benzylic C-H bonds have been the preferred reaction sites for the above catalytic systems, whereas very few examples of the tosylamidation of unactivated C-H bonds have been reported to date. Thus, the conversion of cyclohexane into N-(p-tolylsulfonyl)- aminocyclohexane has been reported only in a few cases, and has never been achieved in yields higher than 20%, based in the nitrene source. 1-3h Another representative example is toluene: in contrast with the common use of ethylbenzene as a probe molecule for this transformation, and the ease with which its secondary sites have been activated, the primary C-H bonds of toluene have remained unreactive by this method for the majority of catalysts reported, with just a few exceptions. 3h,5 The extreme case of a molecule of considerable interest to be converted into an amine is benzene: aniline is currently obtained by indirect methods that require the conversion of benzene into other derivatives such as nitro- or chlorobenzene, or into phenol as an intermediate step. Despite that interest, very few examples for the amination of benzene have been reported to date. 8 In recent years we have studied the use of copper(I)-homoscor- pionate 9 complexes as catalysts for the carbene, 10 nitrene, 11 and oxo 12 transfer reactions to a variety of substrates. Now we have turned our attention toward the amination of C-H bonds, and we have tested the catalytic capabilities of this type of complex toward such transformation. We have chosen TpBr 3 Cu(NCMe) (1), a compound that is readily prepared by direct reaction of TlTp Br3 and CuI to carry out this preliminary study. 10h When PhINTs 13 (0.5 mmol) was added to a solution of 1 (0.025 mmol) in neat toluene (10 mL), the initial suspension gradually converted into a solution. After 1 h of stirring, a clear, greenish solution was obtained. GC and NMR studies revealed the quantitative conversion of toluene into N-(p-tolylsulfonyl)aminotoluene (eq 2). As mentioned above, other authors have reported related transformations in low yields. Thus, Che et al. 3h reported a 11% yield for the stoichiometric transfer from a ruthenium complex, whereas Cenini and co-workers 5 obtained even lower conversions of such amines when using cobalt-porphyrin catalysts and azides as the nitrene source. The related reaction with mesitylene has also been investigated, with very similar results: quantitative conversion of the nitrene source into the corresponding amine (eq 3) has been observed. To our knowledge, the activation of such primary C-H bonds of toluene † Universidad de Huelva. ‡ University of Delaware. Scheme 1. Usual Substrates Employed in the Metal-Catalyzed Tosylamidation Reaction by Nitrene Insertion; Arrow Indicates the Reaction Site Published on Web 09/12/2003 12078 9 J. AM. CHEM. SOC. 2003, 125, 12078-12079 10.1021/ja037072l CCC: $25.00 © 2003 American Chemical Society