Selective C-Arylation of Free (NH)-Hetroarenes via Catalytic C-H bond Functionalisation

Sezen and Sames have reported a novel palladium catalysed arylation of unsubstituted heteroaromatics without the need for prior halogenation of the heteroaromatic.  Under optimised conditions the reaction of the Grignard reagent formed by the reaction of indole with ethyl magnesium bromide or magnesium oxide is reacted with for example 4-iodotoluene (1.2 equiv), palladium acetate (5 mol %), triphenylphosphine (20 mol %),  in dioxane to give exclusively 2-(4-tolyl)indole with no trace of other isomers or bis-arylated products.  The reaction seems to tolerate electron withdrawing and electron donating groups in the para position of the aryl iodide (such as Me, OMe, F, CF₃, COMe), with yields in the region 75-90%.  Interestingly when the reaction is carried out with 2-iodotoluene 2 equivalents of 2-iodotoluene are required and a mixture of 2-(o-tolyl)indole (53%) and 1-(o-tolyl)indole (17%) is obtained.  The reaction has been applied to other NH-heteroaromatics such as pyrrole, pyrazole, and imidazole with a single product being obtained in each case.

Specifically pyrrole gave 2-phenylpyrrole in 86% yield, pyrazole gave 2-phenylpyrazole in 81% yield, and imidazole gave 4-phenylimidazole in 72% yield  The regioselectivity of the arylation of imidazole can be altered by adding a co-catalyst such as copper iodide.  Under these conditions the reaction produces 2-phenylimidazole in 83% yield.  Similarly 2-phenylbenzimidazole was formed in 90% yield and 2-phenylpyrimidine was formed in 78%  yield.  N-Arylation is also possible if an alkali metal base is used in place of a Grignard reagent provided a suitable ligand (such as DPPF, tBu₃P etc) is added.  (J. Am. Chem. Soc., 2003, 125, 5274-5275).

The Dienyl Pauson-Khand Reaction
A study aimed at determining whether intermediates in the [4+2] cycloaddition of dienynes could be trapped with CO has led to the development of a dienyl Pauson-Khand reaction by Wender and co-workers.  In principle multifunctional compounds such as (1) can react by a number of pathways, but by optimising the reaction conditions and the solvent a high yield (89%) of (2) can be realised.

Interestingly the yield was improved by reducing the catalyst loading ([RhCl(CO)(PPh₃)₂] – AgSbF₆) and this also allowed the reaction to be carried out under 1 atmosphere of CO.  In addition this must be one of the few examples in the literature where the isolated yield of product (89%) is higher than the GC yield in solution (88%), albeit only just!  (Angew. Chem. Internat. Ed.. 2003, 42, 1853-1857).