Copper-Catalyzed Amination of Primary Benzylic C-H Bonds with Primary and Secondary Sulfonamides

Once again a case of C-H activation, this time for benzylic substrates.

As we have commented in previous issues of our newsletter, C-H activation is one of the hottest topics in Organic Synthesis. Dozens of papers are being published each year, many of then allowing transformations that were just a dream some years ago. Additionally, the introduction of a nitrogen atom via an organometallic coupling, that is, the construction of a C-N bond, has been also one of the most growing fields in the last years. Now join the two topics and you have a winner.

Powell (Merck Frosst, Canada) has just published a paper related with the direct activation of benzylic C-H bonds as a way to introduce nitrogen atoms, more specifically sulfonamides. As the author states in the introduction, though some work has been done for the direct amination of C-H bonds, the benzylic substrates usually afford low yields. The method they have developed tries to solve this problem by using a Copper catalyst with moderate success. In a typical procedure, a toluene is mixed with a sulfonamide in the presence of [MeCN]4Cu(I)PF6 (10 mol%), 1,3-indanedione (15 mol %) at room temperature for 15 min. Then 3-CF3C6H4CO3t-Bu oxidant (2 equiv) is added in a single addition and the mixture stirred for three days at room temperature.

Yields are only moderate, reaction times are long and no heterocycles are used. However, the method is quite simple and allows the use of a wide range of sulfonamides, both primary and secondary, starting materials which are readily available. Something to consider the next time you need products like these…

J. Org. Chem., 2010, 75 (8), pp 2726–2729. See: 10.1021/jo100197r