Ruthenium-catalyzed cyclocarbonylation of aliphatic amides through the regioselective activation of unactivated C(sp3)–H bonds

Abstract

The regioselective carbonylation of unactivated C(sp3)–H bonds of aliphatic amides, using 2-pyridinylmethylamine as a directing group in conjunction with Ru3(CO)12 as a catalyst is described. The presence of a 2-pyridinylmethylamine moiety in the amides is crucial for the success of the reaction. Although ethylene is not incorporated into the products, its presence is also essential for the reaction to proceed. Furthermore, the addition of H2O is important for the reaction to proceed efficiently. The reaction shows a high preference for the C–H bonds of methyl groups, compared to methylene C–H bonds, even the methylene C–H bonds are activated by the presence of an oxygen atom or an aryl group. In addition, the reaction tolerates various functional groups, such as MeO, Cl, CF3, CN, and even Br substituents. The reaction of α-mono-substituted aliphatic amides gave the corresponding carbonylation products in lower yields, although the use of α,α-di-substituted aliphatic amides resulted in high product yields. The use of a sterically demanding directing group, such as 1-(2-pyridinylethyl)amine moiety, in α-mono-substituted aliphatic amides improved the yields of the products. The stoichiometric reaction of an amide with Ru3(CO)12 gave a stable di-nuclear ruthenium complex as a single ruthenium complex in which the 2-pyridinylmethylamino moiety is coordinated to the ruthenium center in a N,N-manner and an amide carbonyl oxygen binds to the other ruthenium center, but C–H bond activation is not involved. The complex itself does not show catalytic activity, but is activated in the presence of H2O under the catalytic reaction conditions employed.